Keyword: non-u.s. gov't
2012 (1)
Preferential encoding of visual categories in parietal cortex compared with prefrontal cortex. Swaminathan, S. K & Freedman, D. J Nat Neurosci, 15(2):315–320, 2012. Place: United States ISBN: 1546-1726
doi abstract bibtex
doi abstract bibtex
The ability to recognize the behavioral relevance, or category membership, of sensory stimuli is critical for interpreting the meaning of events in our environment. Neurophysiological studies of visual categorization have found categorical representations of stimuli in prefrontal cortex (PFC), an area that is closely associated with cognitive and executive functions. Recent studies have also identified neuronal category signals in parietal areas that are typically associated with visual-spatial processing. It has been proposed that category-related signals in parietal cortex and other visual areas may result from 'top-down' feedback from PFC. We directly compared neuronal activity in the lateral intraparietal (LIP) area and PFC in monkeys performing a visual motion categorization task. We found that LIP showed stronger, more reliable and shorter latency category signals than PFC. These findings suggest that LIP is strongly involved in visual categorization and argue against the idea that parietal category signals arise as a result of feedback from PFC during this task
@article{swaminathan_preferential_2012,
title = {Preferential encoding of visual categories in parietal cortex compared with prefrontal cortex.},
volume = {15},
doi = {10.1038/nn.3016},
abstract = {The ability to recognize the behavioral relevance, or category membership, of sensory stimuli is critical for interpreting the meaning of events in our environment. Neurophysiological studies of visual categorization have found categorical representations of stimuli in prefrontal cortex (PFC), an area that is closely associated with cognitive and executive functions. Recent studies have also identified neuronal category signals in parietal areas that are typically associated with visual-spatial processing. It has been proposed that category-related signals in parietal cortex and other visual areas may result from 'top-down' feedback from PFC. We directly compared neuronal activity in the lateral intraparietal (LIP) area and PFC in monkeys performing a visual motion categorization task. We found that LIP showed stronger, more reliable and shorter latency category signals than PFC. These findings suggest that LIP is strongly involved in visual categorization and argue against the idea that parietal category signals arise as a result of feedback from PFC during this task},
language = {eng},
number = {2},
journal = {Nat Neurosci},
author = {Swaminathan, Sruthi K and Freedman, David J},
year = {2012},
pmid = {22246435},
note = {Place: United States
ISBN: 1546-1726},
keywords = {Action Potentials, Analysis of Variance, Animals, Brain Mapping, Macaca mulatta, Male, Parietal Lobe, Photic Stimulation, Prefrontal Cortex, ROC Curve, Sensory Receptor Cells, Visual Fields, Visual Pathways, research support, n.i.h., extramural, research support, non-u.s. gov't, research support, u.s. gov't, non-p.h.s.},
pages = {315--320},
}2009 (1)
A face feature space in the macaque temporal lobe. Freiwald, W. A, Tsao, D. Y, & Livingstone, M. S Nat Neurosci, 12(9):1187–1196, 2009. Place: United States ISBN: 1546-1726
doi abstract bibtex
doi abstract bibtex
The ability of primates to effortlessly recognize faces has been attributed to the existence of specialized face areas. One such area, the macaque middle face patch, consists almost entirely of cells that are selective for faces, but the principles by which these cells analyze faces are unknown. We found that middle face patch neurons detect and differentiate faces using a strategy that is both part based and holistic. Cells detected distinct constellations of face parts. Furthermore, cells were tuned to the geometry of facial features. Tuning was most often ramp-shaped, with a one-to-one mapping of feature magnitude to firing rate. Tuning amplitude depended on the presence of a whole, upright face and features were interpreted according to their position in a whole, upright face. Thus, cells in the middle face patch encode axes of a face space specialized for whole, upright faces
@article{freiwald_face_2009,
title = {A face feature space in the macaque temporal lobe.},
volume = {12},
doi = {10.1038/nn.2363},
abstract = {The ability of primates to effortlessly recognize faces has been attributed to the existence of specialized face areas. One such area, the macaque middle face patch, consists almost entirely of cells that are selective for faces, but the principles by which these cells analyze faces are unknown. We found that middle face patch neurons detect and differentiate faces using a strategy that is both part based and holistic. Cells detected distinct constellations of face parts. Furthermore, cells were tuned to the geometry of facial features. Tuning was most often ramp-shaped, with a one-to-one mapping of feature magnitude to firing rate. Tuning amplitude depended on the presence of a whole, upright face and features were interpreted according to their position in a whole, upright face. Thus, cells in the middle face patch encode axes of a face space specialized for whole, upright faces},
language = {eng},
number = {9},
journal = {Nat Neurosci},
author = {Freiwald, Winrich A and Tsao, Doris Y and Livingstone, Margaret S},
year = {2009},
pmid = {19668199},
note = {Place: United States
ISBN: 1546-1726},
keywords = {Action Potentials, Analysis of Variance, Animals, Face, Macaca mulatta, Magnetic Resonance Imaging, Male, Microelectrodes, Neurons, Photic Stimulation, Temporal Lobe, Time Factors, Visual Perception, research support, n.i.h., extramural, research support, non-u.s. gov't},
pages = {1187--1196},
}2007 (5)
Object category structure in response patterns of neuronal population in monkey inferior temporal cortex. Kiani, R., Esteky, H., Mirpour, K., & Tanaka, K. J Neurophysiol, 97(6):4296–4309, 2007. Place: United States ISBN: 0022-3077
doi abstract bibtex
doi abstract bibtex
Our mental representation of object categories is hierarchically organized, and our rapid and seemingly effortless categorization ability is crucial for our daily behavior. Here, we examine responses of a large number (\textgreater600) of neurons in monkey inferior temporal (IT) cortex with a large number (\textgreater1,000) of natural and artificial object images. During the recordings, the monkeys performed a passive fixation task. We found that the categorical structure of objects is represented by the pattern of activity distributed over the cell population. Animate and inanimate objects created distinguishable clusters in the population code. The global category of animate objects was divided into bodies, hands, and faces. Faces were divided into primate and nonprimate faces, and the primate-face group was divided into human and monkey faces. Bodies of human, birds, and four-limb animals clustered together, whereas lower animals such as fish, reptile, and insects made another cluster. Thus the cluster analysis showed that IT population responses reconstruct a large part of our intuitive category structure, including the global division into animate and inanimate objects, and further hierarchical subdivisions of animate objects. The representation of categories was distributed in several respects, e.g., the similarity of response patterns to stimuli within a category was maintained by both the cells that maximally responded to the category and the cells that responded weakly to the category. These results advance our understanding of the nature of the IT neural code, suggesting an inherently categorical representation that comprises a range of categories including the amply investigated face category.
@article{kiani_object_2007,
title = {Object category structure in response patterns of neuronal population in monkey inferior temporal cortex.},
volume = {97},
doi = {10.1152/jn.00024.2007},
abstract = {Our mental representation of object categories is hierarchically organized, and our rapid and seemingly effortless categorization ability is crucial for our daily behavior. Here, we examine responses of a large number ({\textgreater}600) of neurons in monkey inferior temporal (IT) cortex with a large number ({\textgreater}1,000) of natural and artificial object images. During the recordings, the monkeys performed a passive fixation task. We found that the categorical structure of objects is represented by the pattern of activity distributed over the cell population. Animate and inanimate objects created distinguishable clusters in the population code. The global category of animate objects was divided into bodies, hands, and faces. Faces were divided into primate and nonprimate faces, and the primate-face group was divided into human and monkey faces. Bodies of human, birds, and four-limb animals clustered together, whereas lower animals such as fish, reptile, and insects made another cluster. Thus the cluster analysis showed that IT population responses reconstruct a large part of our intuitive category structure, including the global division into animate and inanimate objects, and further hierarchical subdivisions of animate objects. The representation of categories was distributed in several respects, e.g., the similarity of response patterns to stimuli within a category was maintained by both the cells that maximally responded to the category and the cells that responded weakly to the category. These results advance our understanding of the nature of the IT neural code, suggesting an inherently categorical representation that comprises a range of categories including the amply investigated face category.},
language = {eng},
number = {6},
journal = {J Neurophysiol},
author = {Kiani, Roozbeh and Esteky, Hossein and Mirpour, Koorosh and Tanaka, Keiji},
year = {2007},
pmid = {17428910},
note = {Place: United States
ISBN: 0022-3077},
keywords = {Action Potentials, Animals, Behavior, Animal, Brain Mapping, Cluster Analysis, Humans, Macaca mulatta, Neurons, Pattern Recognition, Visual, Photic Stimulation, Probability, Reaction Time, Temporal Lobe, Visual Pathways, research support, non-u.s. gov't},
pages = {4296--4309},
}Invariant object recognition with trace learning and multiple stimuli present during training. Stringer, S M, Rolls, E T, & Tromans, J M Network, 18(2):161–187, 2007. Place: England ISBN: 0954-898X
doi abstract bibtex
doi abstract bibtex
Over successive stages, the ventral visual system develops neurons that respond with view, size and position invariance to objects including faces. A major challenge is to explain how invariant representations of individual objects could develop given visual input from environments containing multiple objects. Here we show that the neurons in a 1-layer competitive network learn to represent combinations of three objects simultaneously present during training if the number of objects in the training set is low (e.g. 4), to represent combinations of two objects as the number of objects is increased to for e.g. 10, and to represent individual objects as the number of objects in the training set is increased further to for e.g. 20. We next show that translation invariant representations can be formed even when multiple stimuli are always present during training, by including a temporal trace in the learning rule. Finally, we show that these concepts can be extended to a multi-layer hierarchical network model (VisNet) of the ventral visual system. This approach provides a way to understand how a visual system can, by self-organizing competitive learning, form separate invariant representations of each object even when each object is presented in a scene with multiple other objects present, as in natural visual scenes.
@article{stringer_invariant_2007,
title = {Invariant object recognition with trace learning and multiple stimuli present during training.},
volume = {18},
doi = {10.1080/09548980701556055},
abstract = {Over successive stages, the ventral visual system develops neurons that respond with view, size and position invariance to objects including faces. A major challenge is to explain how invariant representations of individual objects could develop given visual input from environments containing multiple objects. Here we show that the neurons in a 1-layer competitive network learn to represent combinations of three objects simultaneously present during training if the number of objects in the training set is low (e.g. 4), to represent combinations of two objects as the number of objects is increased to for e.g. 10, and to represent individual objects as the number of objects in the training set is increased further to for e.g. 20. We next show that translation invariant representations can be formed even when multiple stimuli are always present during training, by including a temporal trace in the learning rule. Finally, we show that these concepts can be extended to a multi-layer hierarchical network model (VisNet) of the ventral visual system. This approach provides a way to understand how a visual system can, by self-organizing competitive learning, form separate invariant representations of each object even when each object is presented in a scene with multiple other objects present, as in natural visual scenes.},
language = {eng},
number = {2},
journal = {Network},
author = {Stringer, S M and Rolls, E T and Tromans, J M},
year = {2007},
pmid = {17966074},
note = {Place: England
ISBN: 0954-898X},
keywords = {Animals, Computer Simulation, Generalization (Psychology), Humans, Learning, Models, Neurological, Neural Networks (Computer), Neurons, Pattern Recognition, Visual, Photic Stimulation, Visual Cortex, Visual Pathways, research support, non-u.s. gov't},
pages = {161--187},
}Unsupervised learning of visual features through spike timing dependent plasticity. Masquelier, T. & Thorpe, S. J PLoS Comput Biol, 3(2):e31, 2007. Place: United States ISBN: 1553-7358
doi abstract bibtex
doi abstract bibtex
Spike timing dependent plasticity (STDP) is a learning rule that modifies synaptic strength as a function of the relative timing of pre- and postsynaptic spikes. When a neuron is repeatedly presented with similar inputs, STDP is known to have the effect of concentrating high synaptic weights on afferents that systematically fire early, while postsynaptic spike latencies decrease. Here we use this learning rule in an asynchronous feedforward spiking neural network that mimics the ventral visual pathway and shows that when the network is presented with natural images, selectivity to intermediate-complexity visual features emerges. Those features, which correspond to prototypical patterns that are both salient and consistently present in the images, are highly informative and enable robust object recognition, as demonstrated on various classification tasks. Taken together, these results show that temporal codes may be a key to understanding the phenomenal processing speed achieved by the visual system and that STDP can lead to fast and selective responses.
@article{masquelier_unsupervised_2007,
title = {Unsupervised learning of visual features through spike timing dependent plasticity.},
volume = {3},
doi = {10.1371/journal.pcbi.0030031},
abstract = {Spike timing dependent plasticity (STDP) is a learning rule that modifies synaptic strength as a function of the relative timing of pre- and postsynaptic spikes. When a neuron is repeatedly presented with similar inputs, STDP is known to have the effect of concentrating high synaptic weights on afferents that systematically fire early, while postsynaptic spike latencies decrease. Here we use this learning rule in an asynchronous feedforward spiking neural network that mimics the ventral visual pathway and shows that when the network is presented with natural images, selectivity to intermediate-complexity visual features emerges. Those features, which correspond to prototypical patterns that are both salient and consistently present in the images, are highly informative and enable robust object recognition, as demonstrated on various classification tasks. Taken together, these results show that temporal codes may be a key to understanding the phenomenal processing speed achieved by the visual system and that STDP can lead to fast and selective responses.},
language = {eng},
number = {2},
journal = {PLoS Comput Biol},
author = {Masquelier, Timothée and Thorpe, Simon J},
year = {2007},
pmid = {17305422},
note = {Place: United States
ISBN: 1553-7358},
keywords = {Action Potentials, Artificial Intelligence, Computer Simulation, Feedback, Models, Neurological, Nerve Net, Neuronal Plasticity, Neurons, Afferent, Pattern Recognition, Visual, Synaptic Transmission, Visual Cortex, research support, non-u.s. gov't},
pages = {e31},
}Modulation of neuronal interactions through neuronal synchronization. Womelsdorf, T., Schoffelen, J., Oostenveld, R., Singer, W., Desimone, R., Engel, A. K, & Fries, P. Science, 316(5831):1609–1612, 2007. Place: United States ISBN: 1095-9203
doi abstract bibtex
doi abstract bibtex
Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.
@article{womelsdorf_modulation_2007,
title = {Modulation of neuronal interactions through neuronal synchronization.},
volume = {316},
doi = {10.1126/science.1139597},
abstract = {Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.},
language = {eng},
number = {5831},
journal = {Science},
author = {Womelsdorf, Thilo and Schoffelen, Jan-Mathijs and Oostenveld, Robert and Singer, Wolf and Desimone, Robert and Engel, Andreas K and Fries, Pascal},
year = {2007},
pmid = {17569862},
note = {Place: United States
ISBN: 1095-9203},
keywords = {Action Potentials, Animals, Cats, Electrodes, Implanted, Electrophysiology, Macaca nemestrina, Male, Nerve Net, Neurons, Parietal Lobe, Temporal Lobe, Visual Pathways, research support, n.i.h., extramural, research support, non-u.s. gov't},
pages = {1609--1612},
}A feedforward architecture accounts for rapid categorization. Serre, T., Oliva, A., & Poggio, T. Proc Natl Acad Sci U S A, 104(15):6424–6429, 2007. Place: United States ISBN: 0027-8424
doi abstract bibtex
doi abstract bibtex
Primates are remarkably good at recognizing objects. The level of performance of their visual system and its robustness to image degradations still surpasses the best computer vision systems despite decades of engineering effort. In particular, the high accuracy of primates in ultra rapid object categorization and rapid serial visual presentation tasks is remarkable. Given the number of processing stages involved and typical neural latencies, such rapid visual processing is likely to be mostly feedforward. Here we show that a specific implementation of a class of feedforward theories of object recognition (that extend the Hubel and Wiesel simple-to-complex cell hierarchy and account for many anatomical and physiological constraints) can predict the level and the pattern of performance achieved by humans on a rapid masked animal vs. non-animal categorization task.
@article{serre_feedforward_2007,
title = {A feedforward architecture accounts for rapid categorization.},
volume = {104},
doi = {10.1073/pnas.0700622104},
abstract = {Primates are remarkably good at recognizing objects. The level of performance of their visual system and its robustness to image degradations still surpasses the best computer vision systems despite decades of engineering effort. In particular, the high accuracy of primates in ultra rapid object categorization and rapid serial visual presentation tasks is remarkable. Given the number of processing stages involved and typical neural latencies, such rapid visual processing is likely to be mostly feedforward. Here we show that a specific implementation of a class of feedforward theories of object recognition (that extend the Hubel and Wiesel simple-to-complex cell hierarchy and account for many anatomical and physiological constraints) can predict the level and the pattern of performance achieved by humans on a rapid masked animal vs. non-animal categorization task.},
language = {eng},
number = {15},
journal = {Proc Natl Acad Sci U S A},
author = {Serre, Thomas and Oliva, Aude and Poggio, Tomaso},
year = {2007},
pmid = {17404214},
note = {Place: United States
ISBN: 0027-8424},
keywords = {Adult, Humans, Models, Neurological, OR Journal Club, Pattern Recognition, Visual, Photic Stimulation, Psychophysics, Recognition (Psychology), Visual Perception, comparative study, research support, n.i.h., extramural, research support, non-u.s. gov't, research support, u.s. gov't, non-p.h.s.},
pages = {6424--6429},
}2006 (3)
Characterization of canine superficial tumors using gray-scale B mode, color flow mapping, and spectral doppler ultrasonography--a multivariate study. Nyman, H., T., Kristensen, A., T., Lee, M., H., Martinussen, T., & McEvoy, F., J. Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association, 47(2):192-198, 2006.
abstract bibtex
abstract bibtex
Superficial tumors are not routinely evaluated by two- or three-dimensional diagnostic imaging methods as part of the staging of canine cancer patients, although superficial tumors are readily imaged by ultrasound. The objectives of this study were to characterize the ultrasonographic patterns of superficial tumors and to evaluate whether ultrasound can help discriminate between benign and malignant tumors in dogs. Superficial tumors (n=132) in 86 dogs were evaluated by B mode, color flow mapping, and spectral Doppler ultrasonography. Size, echogenicity, tumor border definition, invasiveness, acoustic transmission, presence and distribution of vascular flow to and within the tumor, as well as perfusion indices were measured. The tumors were classified as lipomas, benign tumors, atypical mammary tumors, and malignant tumors. Multivariate statistics using discriminant analysis was used to determine which parameters may be used to predict the status of the tumor. Tumor echogenicity, border shape, acoustic shadowing, total number of vessels to the tumor and the total flow amount are the parameters that in combination resulted in the lowest classification error (24%), meaning that on average three out of four tumors were correctly classified using these parameters. All the lipomas and atypical mammary tumors were classified correctly by ultrasonography. The results of this study show that ultrasonography has an important role in the evaluation of canine superficial tumors, particularly in the evaluation of tissue homogeneity and tumor vascularity.
@article{
title = {Characterization of canine superficial tumors using gray-scale B mode, color flow mapping, and spectral doppler ultrasonography--a multivariate study},
type = {article},
year = {2006},
identifiers = {[object Object]},
keywords = {Animals,Dog Diseases/pathology/physiopathology/ultrasonogr,Dogs,Female,Lipoma/blood supply/ultrasonography/veterinary,Male,Multivariate Analysis,Neoplasm Metastasis,Predictive Value of Tests,Pulsatile Flow,Regional Blood Flow,Research Support, Non-U.S. Gov't,Soft Tissue Neoplasms/blood supply/ultrasonography,Ultrasonography, Doppler, Color/veterinary},
pages = {192-198},
volume = {47},
city = {Department of Small Animal Clinical Sciences, The Royal Veterinary and Agricultural University Copenhagen, Dyrlaegevej 16, 1870 Frederiksberg C, Denmark. helena@dsr.kvl.dv},
id = {bf3d3202-f876-3f19-b88c-c47b56be7064},
created = {2016-09-06T13:34:42.000Z},
file_attached = {false},
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last_modified = {2016-09-07T14:54:39.000Z},
read = {false},
starred = {false},
authored = {true},
confirmed = {true},
hidden = {false},
source_type = {JOUR},
notes = {LR: 20061107; PUBM: Print; JID: 9209635; ppublish},
abstract = {Superficial tumors are not routinely evaluated by two- or three-dimensional diagnostic imaging methods as part of the staging of canine cancer patients, although superficial tumors are readily imaged by ultrasound. The objectives of this study were to characterize the ultrasonographic patterns of superficial tumors and to evaluate whether ultrasound can help discriminate between benign and malignant tumors in dogs. Superficial tumors (n=132) in 86 dogs were evaluated by B mode, color flow mapping, and spectral Doppler ultrasonography. Size, echogenicity, tumor border definition, invasiveness, acoustic transmission, presence and distribution of vascular flow to and within the tumor, as well as perfusion indices were measured. The tumors were classified as lipomas, benign tumors, atypical mammary tumors, and malignant tumors. Multivariate statistics using discriminant analysis was used to determine which parameters may be used to predict the status of the tumor. Tumor echogenicity, border shape, acoustic shadowing, total number of vessels to the tumor and the total flow amount are the parameters that in combination resulted in the lowest classification error (24%), meaning that on average three out of four tumors were correctly classified using these parameters. All the lipomas and atypical mammary tumors were classified correctly by ultrasonography. The results of this study show that ultrasonography has an important role in the evaluation of canine superficial tumors, particularly in the evaluation of tissue homogeneity and tumor vascularity.},
bibtype = {article},
author = {Nyman, H T and Kristensen, A T and Lee, M H and Martinussen, T and McEvoy, F J},
journal = {Veterinary radiology & ultrasound : the official journal of the American College of Veterinary Radiology and the International Veterinary Radiology Association},
number = {2}
}The fate of mutations surfing on the wave of a range expansion. Klopfstein, S., Currat, M., & Excoffier, L. Mol Biol Evol, 23(3):482-490, 2006.
![The fate of mutations surfing on the wave of a range expansion [pdf]](https://bibbase.org/img/filetypes/pdf.svg "pdf")
Paper ![The fate of mutations surfing on the wave of a range expansion [link]](https://bibbase.org/img/filetypes/link.svg "link")
Website abstract bibtex
Paper Website abstract bibtex Many species, including humans, have dramatically expanded their range in the past, and such range expansions had certainly an impact on their genetic diversity. For example, mutations arising in populations at the edge of a range expansion can sometimes surf on the wave of advance and thus reach a larger spatial distribution and a much higher frequency than would be expected in stationary populations. We study here this surfing phenomenon in more detail, by performing extensive computer simulations under a two-dimensional stepping-stone model. We find that the probability of survival of a new mutation depends to a large degree on its proximity to the edge of the wave. Demographic factors such as deme size, migration rate, and local growth rate also influence the fate of these new mutations. We also find that the final spatial and frequency distributions depend on the local deme size of a subdivided population. This latter result is discussed in the light of human expansions in Europe as it should allow one to distinguish between mutations having spread with Paleolithic or Neolithic expansions. By favoring the spread of new mutations, a consequence of the surfing phenomenon is to increase the rate of evolution of spatially expanding populations.
@article{
title = {The fate of mutations surfing on the wave of a range expansion},
type = {article},
year = {2006},
identifiers = {[object Object]},
keywords = {*Genetics, Population,*Geography,*Models, Genetic,*Mutation,Animals,Computer Simulation,Demography,Europe,Humans,Population Density,Research Support, Non-U.S. Gov't,Software},
pages = {482-490},
volume = {23},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16280540},
id = {e8b34b18-45f3-3c34-9619-fa45f993815d},
created = {2017-06-19T13:43:37.402Z},
file_attached = {true},
profile_id = {de68dde1-2ff3-3a4e-a214-ef424d0c7646},
group_id = {b2078731-0913-33b9-8902-a53629a24e83},
last_modified = {2017-06-19T13:43:37.526Z},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>0737-4038 (Print)<m:linebreak/>Journal Article</m:note>},
abstract = {Many species, including humans, have dramatically expanded their range in the past, and such range expansions had certainly an impact on their genetic diversity. For example, mutations arising in populations at the edge of a range expansion can sometimes surf on the wave of advance and thus reach a larger spatial distribution and a much higher frequency than would be expected in stationary populations. We study here this surfing phenomenon in more detail, by performing extensive computer simulations under a two-dimensional stepping-stone model. We find that the probability of survival of a new mutation depends to a large degree on its proximity to the edge of the wave. Demographic factors such as deme size, migration rate, and local growth rate also influence the fate of these new mutations. We also find that the final spatial and frequency distributions depend on the local deme size of a subdivided population. This latter result is discussed in the light of human expansions in Europe as it should allow one to distinguish between mutations having spread with Paleolithic or Neolithic expansions. By favoring the spread of new mutations, a consequence of the surfing phenomenon is to increase the rate of evolution of spatially expanding populations.},
bibtype = {article},
author = {Klopfstein, S and Currat, M and Excoffier, L},
journal = {Mol Biol Evol},
number = {3}
}Two retinotopic visual areas in human lateral occipital cortex. Larsson, J. & Heeger, D. J J Neurosci, 26(51):13128–13142, 2006. Place: United States ISBN: 1529-2401
doi abstract bibtex
doi abstract bibtex
We describe two visual field maps, lateral occipital areas 1 (LO1) and 2 (LO2), in the human lateral occipital cortex between the dorsal part of visual area V3 and visual area V5/MT+. Each map contained a topographic representation of the contralateral visual hemifield. The eccentricity representations were shared with V1/V2/V3. The polar angle representation in LO1 extended from the lower vertical meridian (at the boundary with dorsal V3) through the horizontal to the upper vertical meridian (at the boundary with LO2). The polar angle representation in LO2 was the mirror-reversal of that in LO1. LO1 and LO2 overlapped with the posterior part of the object-selective lateral occipital complex and the kinetic occipital region (KO). The retinotopy and functional properties of LO1 and LO2 suggest that they correspond to two new human visual areas, which lack exact homologues in macaque visual cortex. The topography, stimulus selectivity, and anatomical location of LO1 and LO2 indicate that they integrate shape information from multiple visual submodalities in retinotopic coordinates.
@article{larsson_two_2006,
title = {Two retinotopic visual areas in human lateral occipital cortex.},
volume = {26},
doi = {10.1523/JNEUROSCI.1657-06.2006},
abstract = {We describe two visual field maps, lateral occipital areas 1 (LO1) and 2 (LO2), in the human lateral occipital cortex between the dorsal part of visual area V3 and visual area V5/MT+. Each map contained a topographic representation of the contralateral visual hemifield. The eccentricity representations were shared with V1/V2/V3. The polar angle representation in LO1 extended from the lower vertical meridian (at the boundary with dorsal V3) through the horizontal to the upper vertical meridian (at the boundary with LO2). The polar angle representation in LO2 was the mirror-reversal of that in LO1. LO1 and LO2 overlapped with the posterior part of the object-selective lateral occipital complex and the kinetic occipital region (KO). The retinotopy and functional properties of LO1 and LO2 suggest that they correspond to two new human visual areas, which lack exact homologues in macaque visual cortex. The topography, stimulus selectivity, and anatomical location of LO1 and LO2 indicate that they integrate shape information from multiple visual submodalities in retinotopic coordinates.},
language = {eng},
number = {51},
journal = {J Neurosci},
author = {Larsson, Jonas and Heeger, David J},
year = {2006},
pmid = {17182764},
note = {Place: United States
ISBN: 1529-2401},
keywords = {Brain Mapping, Humans, Motion Perception, Occipital Lobe, Photic Stimulation, Retina, Visual Cortex, Visual Fields, Visual Pathways, research support, n.i.h., extramural, research support, non-u.s. gov't},
pages = {13128--13142},
}2005 (4)
Mapping genes of complex psychiatric diseases in Daghestan genetic isolates. Bulayeva, K., B., Leal, S., M., Pavlova, T., A., Kurbanov, R., M., Glatt, S., J., Bulayev, O., A., & Tsuang, M., T. Am J Med Genet B Neuropsychiatr Genet, 132(1):76-84, 2005.
Paper Website abstract bibtex
Paper Website abstract bibtex Genetic isolates, which provide outstanding opportunities for identification of susceptibility genes for complex diseases, can be classified as primary (having an ancient demographic history in a stable environment) or secondary (having a younger demographic history) Neel [1992: Minority populations: Genetics, demography, and health, pp. 1-13]. Daghestan contains 26 out of 50 indigenous Caucasus ethnicities that have been in existence for hundreds of generations in the same highland region. The ethnic groups are subdivided into numerous primary isolates. The founder effect and gene drift in these primary isolates may have caused aggregation of specific haplotypes with limited numbers of pathogenic alleles and loci in some isolates relative to others. These are expressed as inter-population differences in lifetime prevalence and features of certain complex clinical phenotypes and in patterns of genetic linkage and linkage disequilibrium (LD). Stable highland and ethnic-cultural environments have led to increased penetrance and a reduced number of phenocopies, which typically hamper the identification of any susceptibility genes for complex diseases. Owing to these characteristics of the primary isolates, a comparative linkage study in the primary isolates allows us to define the number of susceptibility genes for any complex disease and to identify the source of variability and non-replication of linkage analysis results. As part of an ongoing study, seven extended schizophrenia and one nonspecific mental retardation kindreds have been ascertained from Daghestan isolates. Lifetime morbid risk for schizophrenia in the isolates varied from 0 to 5%. A genome scan with markers spaced 10 cM apart was carried out on these pedigrees and linkage analysis was performed using descent graph methods, as implemented in Simwalk2. To identify regions containing susceptibility genes within these kindreds, we followed up those regions with non-parametric and parametric linkage analyses, with the choice of genetic model guided by the results obtained in the NPL. While the analyses are ongoing, the most positive findings were made in different isolated pedigrees on chromosomes 17p11, 3q24, and 22q for schizophrenia and on chromosome 12q for nonspecific mental retardation.
@article{
title = {Mapping genes of complex psychiatric diseases in Daghestan genetic isolates},
type = {article},
year = {2005},
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pages = {76-84},
volume = {132},
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abstract = {Genetic isolates, which provide outstanding opportunities for identification of susceptibility genes for complex diseases, can be classified as primary (having an ancient demographic history in a stable environment) or secondary (having a younger demographic history) Neel [1992: Minority populations: Genetics, demography, and health, pp. 1-13]. Daghestan contains 26 out of 50 indigenous Caucasus ethnicities that have been in existence for hundreds of generations in the same highland region. The ethnic groups are subdivided into numerous primary isolates. The founder effect and gene drift in these primary isolates may have caused aggregation of specific haplotypes with limited numbers of pathogenic alleles and loci in some isolates relative to others. These are expressed as inter-population differences in lifetime prevalence and features of certain complex clinical phenotypes and in patterns of genetic linkage and linkage disequilibrium (LD). Stable highland and ethnic-cultural environments have led to increased penetrance and a reduced number of phenocopies, which typically hamper the identification of any susceptibility genes for complex diseases. Owing to these characteristics of the primary isolates, a comparative linkage study in the primary isolates allows us to define the number of susceptibility genes for any complex disease and to identify the source of variability and non-replication of linkage analysis results. As part of an ongoing study, seven extended schizophrenia and one nonspecific mental retardation kindreds have been ascertained from Daghestan isolates. Lifetime morbid risk for schizophrenia in the isolates varied from 0 to 5%. A genome scan with markers spaced 10 cM apart was carried out on these pedigrees and linkage analysis was performed using descent graph methods, as implemented in Simwalk2. To identify regions containing susceptibility genes within these kindreds, we followed up those regions with non-parametric and parametric linkage analyses, with the choice of genetic model guided by the results obtained in the NPL. While the analyses are ongoing, the most positive findings were made in different isolated pedigrees on chromosomes 17p11, 3q24, and 22q for schizophrenia and on chromosome 12q for nonspecific mental retardation.},
bibtype = {article},
author = {Bulayeva, K B and Leal, S M and Pavlova, T A and Kurbanov, R M and Glatt, S J and Bulayev, O A and Tsuang, M T},
journal = {Am J Med Genet B Neuropsychiatr Genet},
number = {1}
}A comparison of linkage disequilibrium patterns and estimated population recombination rates across multiple populations. Evans, D., M. & Cardon, L., R. Am J Hum Genet, 76(4):681-687, 2005.
Paper Website abstract bibtex
Paper Website abstract bibtex Large-scale studies of linkage disequilibrium (LD) have shown considerable variation in the extent and distribution of pairwise LD within and between populations. Taken at face value, these results suggest that genomewide LD maps for one population may not be generalizable to other populations. However, at least part of this diversity is due to some undesirable features of pairwise LD measures, which are well documented for the D' and r2 measures. In this report, we compare patterns of LD derived from pairwise measures with statistical estimates of population recombination rates ( rho ) along a 10-Mb stretch of chromosome 20 in four population samples, comprising East Asians, African Americans, and U.K. and U.S. individuals of western European descent. The results reveal the expected variability of D' within and between populations but show better concordance in estimates of r2 for the same markers across the population samples. Estimates of rho correlate well across populations, but there is still evidence of population-specific spikes and troughs in rho values. We conclude that it is unlikely that a single haplotype map will provide a definitive guide for association studies of many populations; rather, multiple maps will need to be constructed to provide the best-possible guides for gene mapping.
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title = {A comparison of linkage disequilibrium patterns and estimated population recombination rates across multiple populations},
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pages = {681-687},
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abstract = {Large-scale studies of linkage disequilibrium (LD) have shown considerable variation in the extent and distribution of pairwise LD within and between populations. Taken at face value, these results suggest that genomewide LD maps for one population may not be generalizable to other populations. However, at least part of this diversity is due to some undesirable features of pairwise LD measures, which are well documented for the D' and r2 measures. In this report, we compare patterns of LD derived from pairwise measures with statistical estimates of population recombination rates ( rho ) along a 10-Mb stretch of chromosome 20 in four population samples, comprising East Asians, African Americans, and U.K. and U.S. individuals of western European descent. The results reveal the expected variability of D' within and between populations but show better concordance in estimates of r2 for the same markers across the population samples. Estimates of rho correlate well across populations, but there is still evidence of population-specific spikes and troughs in rho values. We conclude that it is unlikely that a single haplotype map will provide a definitive guide for association studies of many populations; rather, multiple maps will need to be constructed to provide the best-possible guides for gene mapping.},
bibtype = {article},
author = {Evans, D M and Cardon, L R},
journal = {Am J Hum Genet},
number = {4}
}Decoding the visual and subjective contents of the human brain. Kamitani, Y. & Tong, F. Nat Neurosci, 8(5):679–685, 2005. Place: United States ISBN: 1097-6256
doi abstract bibtex
doi abstract bibtex
The potential for human neuroimaging to read out the detailed contents of a person's mental state has yet to be fully explored. We investigated whether the perception of edge orientation, a fundamental visual feature, can be decoded from human brain activity measured with functional magnetic resonance imaging (fMRI). Using statistical algorithms to classify brain states, we found that ensemble fMRI signals in early visual areas could reliably predict on individual trials which of eight stimulus orientations the subject was seeing. Moreover, when subjects had to attend to one of two overlapping orthogonal gratings, feature-based attention strongly biased ensemble activity toward the attended orientation. These results demonstrate that fMRI activity patterns in early visual areas, including primary visual cortex (V1), contain detailed orientation information that can reliably predict subjective perception. Our approach provides a framework for the readout of fine-tuned representations in the human brain and their subjective contents.
@article{kamitani_decoding_2005,
title = {Decoding the visual and subjective contents of the human brain.},
volume = {8},
doi = {10.1038/nn1444},
abstract = {The potential for human neuroimaging to read out the detailed contents of a person's mental state has yet to be fully explored. We investigated whether the perception of edge orientation, a fundamental visual feature, can be decoded from human brain activity measured with functional magnetic resonance imaging (fMRI). Using statistical algorithms to classify brain states, we found that ensemble fMRI signals in early visual areas could reliably predict on individual trials which of eight stimulus orientations the subject was seeing. Moreover, when subjects had to attend to one of two overlapping orthogonal gratings, feature-based attention strongly biased ensemble activity toward the attended orientation. These results demonstrate that fMRI activity patterns in early visual areas, including primary visual cortex (V1), contain detailed orientation information that can reliably predict subjective perception. Our approach provides a framework for the readout of fine-tuned representations in the human brain and their subjective contents.},
language = {eng},
number = {5},
journal = {Nat Neurosci},
author = {Kamitani, Yukiyasu and Tong, Frank},
year = {2005},
pmid = {15852014},
note = {Place: United States
ISBN: 1097-6256},
keywords = {Adult, Algorithms, Attention, Brain Mapping, Cognition, Evoked Potentials, Visual, Humans, MR Methods, Magnetic Resonance Imaging, Models, Neurological, Orientation, Pattern Recognition, Visual, Photic Stimulation, Visual Cortex, Visual Pathways, Visual Perception, research support, n.i.h., extramural, research support, non-u.s. gov't, research support, u.s. gov't, p.h.s.},
pages = {679--685},
}How close are we to understanding v1?. Olshausen, B. A & Field, D. J Neural Comput, 17(8):1665–1699, 2005. Place: United States ISBN: 0899-7667
doi abstract bibtex
doi abstract bibtex
A wide variety of papers have reviewed what is known about the function of primary visual cortex. In this review, rather than stating what is known, we attempt to estimate how much is still unknown about V1 function. In particular, we identify five problems with the current view of V1 that stem largely from experimental and theoretical biases, in addition to the contributions of nonlinearities in the cortex that are not well understood. Our purpose is to open the door to new theories, a number of which we describe, along with some proposals for testing them.
@article{olshausen_how_2005,
title = {How close are we to understanding v1?},
volume = {17},
doi = {10.1162/0899766054026639},
abstract = {A wide variety of papers have reviewed what is known about the function of primary visual cortex. In this review, rather than stating what is known, we attempt to estimate how much is still unknown about V1 function. In particular, we identify five problems with the current view of V1 that stem largely from experimental and theoretical biases, in addition to the contributions of nonlinearities in the cortex that are not well understood. Our purpose is to open the door to new theories, a number of which we describe, along with some proposals for testing them.},
language = {eng},
number = {8},
journal = {Neural Comput},
author = {Olshausen, Bruno A and Field, David J},
year = {2005},
pmid = {15969914},
note = {Place: United States
ISBN: 0899-7667},
keywords = {Animals, Bias (Epidemiology), Humans, Models, Neurological, Neurons, Nonlinear Dynamics, Visual Cortex, Visual Pathways, comparative study, research support, non-u.s. gov't, review},
pages = {1665--1699},
}2004 (5)
Clinical phenotype of families with longevity. Atzmon, G., Schechter, C., Greiner, W., Davidson, D., Rennert, G., & Barzilai, N. J Am Geriatr Soc, 52(2):274-277, 2004.
Paper Website abstract bibtex
Paper Website abstract bibtex OBJECTIVES: To determine whether offspring of centenarians acquired protection from age-related diseases. DESIGN: Case-control study. SETTING: The study was part of the Longevity Genes Project at Albert Einstein College of Medicine. PARTICIPANTS: Centenarians (n=145), offspring of centenarians (n=180), and spouses of the offspring of centenarians (n=75) as a control group. Two additional groups served as controls: age-matched Ashkenazi Jews, and an age-matched control group from the Third National Health and Nutrition Examination Survey. MEASUREMENTS: Self-reported family history of longevity; prevalence of hypertension, diabetes mellitus, heart attacks, and strokes; and objective measurements of body mass index and fat mass. RESULTS: Parents of centenarians (born in approximately 1870) had a markedly greater ( approximately sevenfold) "risk" for longevity (reaching ages 90-99), supporting the notion that genetics contributed to longevity in these families. The offspring of long-lived parents had significantly lower prevalence of hypertension (by 23%), diabetes mellitus (by 50%), heart attacks (by 60%), and strokes (no events reported) than several age-matched control groups. CONCLUSION: Offspring of centenarians may inherit significantly better health. The authors suggest that a cohort of these subjects and their spouses is ideal to study the phenotype and genotype of longevity and its interaction with the environment.
@article{
title = {Clinical phenotype of families with longevity},
type = {article},
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pages = {274-277},
volume = {52},
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abstract = {OBJECTIVES: To determine whether offspring of centenarians acquired protection from age-related diseases. DESIGN: Case-control study. SETTING: The study was part of the Longevity Genes Project at Albert Einstein College of Medicine. PARTICIPANTS: Centenarians (n=145), offspring of centenarians (n=180), and spouses of the offspring of centenarians (n=75) as a control group. Two additional groups served as controls: age-matched Ashkenazi Jews, and an age-matched control group from the Third National Health and Nutrition Examination Survey. MEASUREMENTS: Self-reported family history of longevity; prevalence of hypertension, diabetes mellitus, heart attacks, and strokes; and objective measurements of body mass index and fat mass. RESULTS: Parents of centenarians (born in approximately 1870) had a markedly greater ( approximately sevenfold) "risk" for longevity (reaching ages 90-99), supporting the notion that genetics contributed to longevity in these families. The offspring of long-lived parents had significantly lower prevalence of hypertension (by 23%), diabetes mellitus (by 50%), heart attacks (by 60%), and strokes (no events reported) than several age-matched control groups. CONCLUSION: Offspring of centenarians may inherit significantly better health. The authors suggest that a cohort of these subjects and their spouses is ideal to study the phenotype and genotype of longevity and its interaction with the environment.},
bibtype = {article},
author = {Atzmon, G and Schechter, C and Greiner, W and Davidson, D and Rennert, G and Barzilai, N},
journal = {J Am Geriatr Soc},
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}Underlying principles of visual shape selectivity in posterior inferotemporal cortex. Brincat, S. L & Connor, C. E Nat Neurosci, 7(8):880–886, 2004. Place: United States ISBN: 1097-6256
doi abstract bibtex
doi abstract bibtex
Object perception depends on shape processing in the ventral visual pathway, which in monkeys culminates in inferotemporal cortex (IT). Here we provide a description of fundamental quantitative principles governing neural selectivity for complex shape in IT. By measuring responses to large, parametric sets of two-dimensional (2D) silhouette shapes, we found that neurons in posterior IT (Brodmann's areas TEO and posterior TE) integrate information about multiple contour elements (straight and curved edge fragments of the type represented in lower-level areas) using both linear and nonlinear mechanisms. This results in complex, distributed response patterns that cannot be characterized solely in terms of example stimuli. We explained these response patterns with tuning functions in multidimensional shape space and accurately predicted neural responses to the widely varying shapes in our stimulus set. Integration of contour element information in earlier stages of IT represents an important step in the transformation from low-level shape signals to complex object representation.
@article{brincat_underlying_2004,
title = {Underlying principles of visual shape selectivity in posterior inferotemporal cortex.},
volume = {7},
doi = {10.1038/nn1278},
abstract = {Object perception depends on shape processing in the ventral visual pathway, which in monkeys culminates in inferotemporal cortex (IT). Here we provide a description of fundamental quantitative principles governing neural selectivity for complex shape in IT. By measuring responses to large, parametric sets of two-dimensional (2D) silhouette shapes, we found that neurons in posterior IT (Brodmann's areas TEO and posterior TE) integrate information about multiple contour elements (straight and curved edge fragments of the type represented in lower-level areas) using both linear and nonlinear mechanisms. This results in complex, distributed response patterns that cannot be characterized solely in terms of example stimuli. We explained these response patterns with tuning functions in multidimensional shape space and accurately predicted neural responses to the widely varying shapes in our stimulus set. Integration of contour element information in earlier stages of IT represents an important step in the transformation from low-level shape signals to complex object representation.},
language = {eng},
number = {8},
journal = {Nat Neurosci},
author = {Brincat, Scott L and Connor, Charles E},
year = {2004},
pmid = {15235606},
note = {Place: United States
ISBN: 1097-6256},
keywords = {Action Potentials, Animals, Form Perception, Macaca mulatta, Models, Neurological, Neurons, Temporal Lobe, Visual Pathways, Visual Perception, research support, non-u.s. gov't, research support, u.s. gov't, p.h.s.},
pages = {880--886},
}Linkage disequilibrium in young genetically isolated Dutch population. Aulchenko, Y., S., Heutink, P., Mackay, I., Bertoli-Avella, A., M., Pullen, J., Vaessen, N., Rademaker, T., A., Sandkuijl, L., A., Cardon, L., Oostra, B., & van Duijn, C., M. Eur J Hum Genet, 12(7):527-534, 2004.
Paper Website abstract bibtex
Paper Website abstract bibtex The design and feasibility of genetic studies of complex diseases are critically dependent on the extent and distribution of linkage disequilibrium (LD) across the genome and between different populations. We have examined genomewide and region-specific LD in a young genetically isolated population identified in the Netherlands by genotyping approximately 800 Short Tandem Repeat markers distributed genomewide across 58 individuals. Several regions were analyzed further using a denser marker map. The permutation-corrected measure of LD was used for analysis. A significant (P<0.0004) relation between LD and genetic distance on a genomewide scale was found. Distance explained 4% of the total LD variation. For fine-mapping data, distance accounted for a larger proportion of LD variation (up to 39%). A notable similarity in the genomewide distribution of LD was revealed between this population and other young genetically isolated populations from Micronesia and Costa Rica. Our study population and experiment was simulated in silico to confirm our knowledge of the history of the population. High agreement was observed between results of analysis of simulated and empirical data. We conclude that our population shows a high level of LD similar to that demonstrated previously in other young genetic isolates. In Europe, there may be a large number of young genetically isolated populations that are similar in history to ours. In these populations, a similar degree of LD is expected and thus they may be effectively used for linkage or LD mapping.
@article{
title = {Linkage disequilibrium in young genetically isolated Dutch population},
type = {article},
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identifiers = {[object Object]},
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pages = {527-534},
volume = {12},
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abstract = {The design and feasibility of genetic studies of complex diseases are critically dependent on the extent and distribution of linkage disequilibrium (LD) across the genome and between different populations. We have examined genomewide and region-specific LD in a young genetically isolated population identified in the Netherlands by genotyping approximately 800 Short Tandem Repeat markers distributed genomewide across 58 individuals. Several regions were analyzed further using a denser marker map. The permutation-corrected measure of LD was used for analysis. A significant (P<0.0004) relation between LD and genetic distance on a genomewide scale was found. Distance explained 4% of the total LD variation. For fine-mapping data, distance accounted for a larger proportion of LD variation (up to 39%). A notable similarity in the genomewide distribution of LD was revealed between this population and other young genetically isolated populations from Micronesia and Costa Rica. Our study population and experiment was simulated in silico to confirm our knowledge of the history of the population. High agreement was observed between results of analysis of simulated and empirical data. We conclude that our population shows a high level of LD similar to that demonstrated previously in other young genetic isolates. In Europe, there may be a large number of young genetically isolated populations that are similar in history to ours. In these populations, a similar degree of LD is expected and thus they may be effectively used for linkage or LD mapping.},
bibtype = {article},
author = {Aulchenko, Y S and Heutink, P and Mackay, I and Bertoli-Avella, A M and Pullen, J and Vaessen, N and Rademaker, T A and Sandkuijl, L A and Cardon, L and Oostra, B and van Duijn, C M},
journal = {Eur J Hum Genet},
number = {7}
}Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis. Frisch, A., Colombo, R., Michaelovsky, E., Karpati, M., Goldman, B., & Peleg, L. Hum Genet, 114(4):366-376, 2004.
Paper Website abstract bibtex
Paper Website abstract bibtex The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs). To investigate the genetic history of this mutation in the AJ population, a conserved haplotype (D15S981:175-D15S131:240-D15S1050:284-D15S197:144-D15S188:418) was identified in 1278insTATC chromosomes from 55 unrelated AJ individuals (15 homozygotes and 40 heterozygotes for the TSD mutation), suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the insertion was found to be 40+/-12 generations (95% confidence interval: 30-50 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 8th-9th century. This corresponds with the demographic expansion of AJs in central Europe, following the founding of the Ashkenaz settlement in the early Middle Ages. The results are consistent with the geographic distribution of the main TSD mutation, 1278insTATC being more common in central Europe, and with the coalescent times of mutations causing two other LSDs, Gaucher disease and mucolipidosis type IV. Evidence for the absence of a determinant positive selection (heterozygote advantage) over the mutation is provided by a comparison between the estimated age of 1278insTATC and the probability of the current AJ frequency of the mutant allele as a function of its age, calculated by use of a branching-process model. Therefore, the founder effect in a rapidly expanding population arising from a bottleneck provides a robust parsimonious hypothesis explaining the spread of 1278insTATC-linked TSD in AJ individuals.
@article{
title = {Origin and spread of the 1278insTATC mutation causing Tay-Sachs disease in Ashkenazi Jews: genetic drift as a robust and parsimonious hypothesis},
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pages = {366-376},
volume = {114},
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source_type = {Journal Article},
notes = {<m:note>0340-6717 (Print)<m:linebreak/>Historical Article<m:linebreak/>Journal Article</m:note>},
abstract = {The 1278insTATC is the most prevalent beta-hexosaminidase A ( HEXA) gene mutation causing Tay-Sachs disease (TSD), one of the four lysosomal storage diseases (LSDs) occurring at elevated frequencies among Ashkenazi Jews (AJs). To investigate the genetic history of this mutation in the AJ population, a conserved haplotype (D15S981:175-D15S131:240-D15S1050:284-D15S197:144-D15S188:418) was identified in 1278insTATC chromosomes from 55 unrelated AJ individuals (15 homozygotes and 40 heterozygotes for the TSD mutation), suggesting the occurrence of a common founder. When two methods were used for analysis of linkage disequilibrium (LD) between flanking polymorphic markers and the disease locus and for the study of the decay of LD over time, the estimated age of the insertion was found to be 40+/-12 generations (95% confidence interval: 30-50 generations), so that the most recent common ancestor of the mutation-bearing chromosomes would date to the 8th-9th century. This corresponds with the demographic expansion of AJs in central Europe, following the founding of the Ashkenaz settlement in the early Middle Ages. The results are consistent with the geographic distribution of the main TSD mutation, 1278insTATC being more common in central Europe, and with the coalescent times of mutations causing two other LSDs, Gaucher disease and mucolipidosis type IV. Evidence for the absence of a determinant positive selection (heterozygote advantage) over the mutation is provided by a comparison between the estimated age of 1278insTATC and the probability of the current AJ frequency of the mutant allele as a function of its age, calculated by use of a branching-process model. Therefore, the founder effect in a rapidly expanding population arising from a bottleneck provides a robust parsimonious hypothesis explaining the spread of 1278insTATC-linked TSD in AJ individuals.},
bibtype = {article},
author = {Frisch, A and Colombo, R and Michaelovsky, E and Karpati, M and Goldman, B and Peleg, L},
journal = {Hum Genet},
number = {4}
}Familial aggregation patterns in mathematical ability. Wijsman, E., M., Robinson, N., M., Ainsworth, K., H., Rosenthal, E., A., Holzman, T., & Raskind, W., H. Behav Genet, 34(1):51-62, 2004.
Paper Website abstract bibtex
Paper Website abstract bibtex Mathematical talent is an asset in modern society both at an individual and a societal level. Environmental factors such as quality of mathematics education undoubtedly affect an individual's performance, and there is some evidence that genetic factors also may play a role. The current study was performed to investigate the feasibility of undertaking genetics studies on mathematical ability. Because the etiology of low ability in mathematics is likely to be multifactorial and heterogeneous, we evaluated families ascertained through a proband with high mathematical performance in grade 7 on the SAT to eliminate, to some degree, adverse environmental factors. Families of sex-matched probands, selected for high verbal performance on the SAT, served as the comparison group. We evaluated a number of proxy measures for their usefulness in the study of clustering of mathematical talent. Given the difficulty of testing mathematics performance across developmental ages, especially with the added complexity of decreasing exposure to formal mathematics concepts post schooling, we also devised a semiquantitative scale that incorporated educational, occupational, and avocational information as a surrogate for an academic mathematics measure. Whereas several proxy measures showed no evidence of a genetic basis, we found that the semiquantitative scale of mathematical talent showed strong evidence of a genetic basis, with a differential response as a function of the performance measure used to select the proband. This observation suggests that there may be a genetic basis to specific mathematical talent, and that specific, as opposed to proxy, investigative measures that are designed to measure such talent in family members could be of benefit for this purpose.
@article{
title = {Familial aggregation patterns in mathematical ability},
type = {article},
year = {2004},
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pages = {51-62},
volume = {34},
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abstract = {Mathematical talent is an asset in modern society both at an individual and a societal level. Environmental factors such as quality of mathematics education undoubtedly affect an individual's performance, and there is some evidence that genetic factors also may play a role. The current study was performed to investigate the feasibility of undertaking genetics studies on mathematical ability. Because the etiology of low ability in mathematics is likely to be multifactorial and heterogeneous, we evaluated families ascertained through a proband with high mathematical performance in grade 7 on the SAT to eliminate, to some degree, adverse environmental factors. Families of sex-matched probands, selected for high verbal performance on the SAT, served as the comparison group. We evaluated a number of proxy measures for their usefulness in the study of clustering of mathematical talent. Given the difficulty of testing mathematics performance across developmental ages, especially with the added complexity of decreasing exposure to formal mathematics concepts post schooling, we also devised a semiquantitative scale that incorporated educational, occupational, and avocational information as a surrogate for an academic mathematics measure. Whereas several proxy measures showed no evidence of a genetic basis, we found that the semiquantitative scale of mathematical talent showed strong evidence of a genetic basis, with a differential response as a function of the performance measure used to select the proband. This observation suggests that there may be a genetic basis to specific mathematical talent, and that specific, as opposed to proxy, investigative measures that are designed to measure such talent in family members could be of benefit for this purpose.},
bibtype = {article},
author = {Wijsman, E M and Robinson, N M and Ainsworth, K H and Rosenthal, E A and Holzman, T and Raskind, W H},
journal = {Behav Genet},
number = {1}
}2003 (9)
Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community. Farrer, L., A., Bowirrat, A., Friedland, R., P., Waraska, K., Korczyn, A., D., & Baldwin, C., T. Hum Mol Genet, 12(4):415-422, 2003.
Paper abstract bibtex
Paper abstract bibtex We have observed an unusually high prevalence of dementia of the Alzheimer type (DAT) in Wadi Ara, an inbred Arab community in northern Israel comprising approximately 850 persons over the age of 60 years. Family studies revealed that more than one-third of the DAT cases are members of one hamula (tribal group) within Wadi Ara. To map chromosomal loci contributing to DAT susceptibility, we conducted a 10 cM scan in a series of five cases and five controls selected from this hamula. Markers from 18 chromosomal regions showed significant allelic association with DAT (P<0.05). Locations on chromosomes 2, 9 and 10 remained significant after testing additional affected and non-demented individuals. Significant associations were also observed for markers on chromosome 12 which overlap with a locus implicated in previous genome scans. Analysis of allele frequency distributions for 12 markers spanning 20 cM on chromosome 9 narrowed the possible location of an DAT susceptibility gene to a 13 cM interval between D9S157 and D9S259 (most significant result: P = 2.3 x 10(-7)). Analysis of 14 markers spanning 24 cM on chromosome 12 narrowed the possible location to a 14 cM interval distal to the LRP1 locus (most significant result: P = 1.3 x 10(-6)). Evidence for linkage on chromosome 9 stemmed primarily from excess homozygosity of marker alleles in cases compared with controls, suggesting that the gene at this location behaves in either a recessive or additive fashion. The unique characteristics of this community together with the emergent human genome data should allow for the rapid identification of DAT genes in these candidate regions.
@article{
title = {Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community},
type = {article},
year = {2003},
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pages = {415-422},
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abstract = {We have observed an unusually high prevalence of dementia of the Alzheimer type (DAT) in Wadi Ara, an inbred Arab community in northern Israel comprising approximately 850 persons over the age of 60 years. Family studies revealed that more than one-third of the DAT cases are members of one hamula (tribal group) within Wadi Ara. To map chromosomal loci contributing to DAT susceptibility, we conducted a 10 cM scan in a series of five cases and five controls selected from this hamula. Markers from 18 chromosomal regions showed significant allelic association with DAT (P<0.05). Locations on chromosomes 2, 9 and 10 remained significant after testing additional affected and non-demented individuals. Significant associations were also observed for markers on chromosome 12 which overlap with a locus implicated in previous genome scans. Analysis of allele frequency distributions for 12 markers spanning 20 cM on chromosome 9 narrowed the possible location of an DAT susceptibility gene to a 13 cM interval between D9S157 and D9S259 (most significant result: P = 2.3 x 10(-7)). Analysis of 14 markers spanning 24 cM on chromosome 12 narrowed the possible location to a 14 cM interval distal to the LRP1 locus (most significant result: P = 1.3 x 10(-6)). Evidence for linkage on chromosome 9 stemmed primarily from excess homozygosity of marker alleles in cases compared with controls, suggesting that the gene at this location behaves in either a recessive or additive fashion. The unique characteristics of this community together with the emergent human genome data should allow for the rapid identification of DAT genes in these candidate regions.},
bibtype = {article},
author = {Farrer, L A and Bowirrat, A and Friedland, R P and Waraska, K and Korczyn, A D and Baldwin, C T},
journal = {Hum Mol Genet},
number = {4}
}The Newfoundland population: a unique resource for genetic investigation of complex diseases. Rahman, P., Jones, A., Curtis, J., Bartlett, S., Peddle, L., Fernandez, B., A., & Freimer, N., B. Hum Mol Genet, 12 Spec No:R167-72, 2003.
Paper Website abstract bibtex
Paper Website abstract bibtex The population of the province of Newfoundland and Labrador is genetically isolated. This isolation is evidenced by an overabundance of several monogenic disorders. The Newfoundland population, like that of other isolates, is now the focus of interest for identification of genes implicated in common diseases. However, the utility of such populations for this purpose remains unproven. In this paper, we review the current genetic architecture of the province, with respect to geographic isolation, homogeneity, founder effect, genetic drift and extended linkage disequilibrium. Based on these factors, we propose that the population of Newfoundland offers many advantages for genetic mapping of common diseases, compared with admixed populations, and even compared with other isolates.
@article{
title = {The Newfoundland population: a unique resource for genetic investigation of complex diseases},
type = {article},
year = {2003},
identifiers = {[object Object]},
keywords = {Founder Effect,Genetic Diseases, Inborn/*genetics,Humans,Linkage Disequilibrium,Newfoundland,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, P.H.S.},
pages = {R167-72},
volume = {12 Spec No},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12915452},
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source_type = {Journal Article},
notes = {<m:note>0964-6906 (Print)<m:linebreak/>Journal Article<m:linebreak/>Review</m:note>},
abstract = {The population of the province of Newfoundland and Labrador is genetically isolated. This isolation is evidenced by an overabundance of several monogenic disorders. The Newfoundland population, like that of other isolates, is now the focus of interest for identification of genes implicated in common diseases. However, the utility of such populations for this purpose remains unproven. In this paper, we review the current genetic architecture of the province, with respect to geographic isolation, homogeneity, founder effect, genetic drift and extended linkage disequilibrium. Based on these factors, we propose that the population of Newfoundland offers many advantages for genetic mapping of common diseases, compared with admixed populations, and even compared with other isolates.},
bibtype = {article},
author = {Rahman, P and Jones, A and Curtis, J and Bartlett, S and Peddle, L and Fernandez, B A and Freimer, N B},
journal = {Hum Mol Genet}
}Understanding the Determinants of Exceptional Longevity. Perls, T. & Terry, D. Ann Intern Med, 139(5 Pt 2):445-449, 2003.
Paper Website abstract bibtex
Paper Website abstract bibtex Centenarians represent an extreme of life expectancy. They achieve their exceptional longevity in part by lacking genetic variations linked to premature death. Pedigree studies have shown a substantial familial component in the ability to survive to extreme old age, and a recent study demonstrated a locus on chromosome 4 linked to exceptional longevity, indicating the likely existence of at least one longevity-enabling gene in humans. The children of centenarians have markedly reduced relative risks for age-related diseases, particularly heart disease, hypertension, and diabetes, and are a promising model for genetic and phenotypic studies of 1) aging slowly relative to the general population and 2) the delay of and perhaps escape from important age-related diseases. These studies and those of other mammals and lower organisms show great promise for the delineation of important environmental and genetic determinants of aging well.
@article{
title = {Understanding the Determinants of Exceptional Longevity},
type = {article},
year = {2003},
identifiers = {[object Object]},
keywords = {*Longevity,Animals,Genes,Humans,Life Expectancy,Non-U.S. Gov't,P.H.S.,Phenotype,Research Support,U.S. Gov't},
pages = {445-449},
volume = {139},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12965974},
id = {c5bf1b72-7d77-39e3-9bef-27367ae5c742},
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last_modified = {2017-06-19T13:42:01.863Z},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note> <m:bold>From Duplicate 2 ( </m:bold> <m:bold> </m:bold><m:bold><m:italic>Understanding the determinants of exceptional longevity</m:italic></m:bold><m:bold> </m:bold> <m:bold> - Perls, T; Terry, D )<m:linebreak/> </m:bold> <m:linebreak/>1539-3704<m:linebreak/>Journal Article<m:linebreak/>Review<m:linebreak/> <m:linebreak/> </m:note>},
abstract = {Centenarians represent an extreme of life expectancy. They achieve their exceptional longevity in part by lacking genetic variations linked to premature death. Pedigree studies have shown a substantial familial component in the ability to survive to extreme old age, and a recent study demonstrated a locus on chromosome 4 linked to exceptional longevity, indicating the likely existence of at least one longevity-enabling gene in humans. The children of centenarians have markedly reduced relative risks for age-related diseases, particularly heart disease, hypertension, and diabetes, and are a promising model for genetic and phenotypic studies of 1) aging slowly relative to the general population and 2) the delay of and perhaps escape from important age-related diseases. These studies and those of other mammals and lower organisms show great promise for the delineation of important environmental and genetic determinants of aging well.},
bibtype = {article},
author = {Perls, Thomas and Terry, Dellara},
journal = {Ann Intern Med},
number = {5 Pt 2}
}Predictors of mortality in 2,249 nonagenarians--the Danish 1905-Cohort Survey. Nybo, H., Petersen, H., C., Gaist, D., Jeune, B., Andersen, K., McGue, M., Vaupel, J., W., & Christensen, K. J Am Geriatr Soc, 51(10):1365-1373, 2003.
Paper Website abstract bibtex
Paper Website abstract bibtex OBJECTIVES: : To elucidate whether well-known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old. DESIGN: : A multidimensional survey of the Danish 1905 cohort conducted in 1998 with follow-up of vital status after 15 months. SETTING: : Denmark. PARTICIPANTS: : All Danes born in 1905, irrespective of physical and mental status were approached. Two thousand two hundred sixty-two persons of 3,600 participated in this survey. MEASUREMENTS: : Professional interviewers collected data concerning sociodemographic factors, smoking, alcohol consumption, body mass index, physical and cognitive performance, and health during a visit at the participant's residency. Cox regression models were used to evaluate predictors of mortality. RESULTS: : Five hundred seventy-nine (25.7%) of the 2,249 participants eligible for the analysis died during the 15 months follow-up. Multivariate analyses showed that marital status, education, smoking, obesity, consumption of alcohol, and number of self-reported diseases were not associated with mortality. Disability and cognitive impairment were significant risk factors in men and women. In addition poor self-rated health was associated with an increase in mortality in women. CONCLUSION: : In the oldest old, several known predictors of mortality, such as sociodemographic factors, smoking, and obesity, have lost their importance, but a high disability level, poor physical and cognitive performance, and self-rated health (women only), predict mortality, which shows that mortality in the oldest old is not a stochastic process.
@article{
title = {Predictors of mortality in 2,249 nonagenarians--the Danish 1905-Cohort Survey},
type = {article},
year = {2003},
identifiers = {[object Object]},
keywords = {Activities of Daily Living,Aged,Aged, 80 and over/*statistics & numerical data,Cohort Studies,Denmark/epidemiology,Female,Geriatric Assessment,Humans,Interviews,Male,Mortality/*trends,Predictive Value of Tests,Proportional Hazards Models,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, P.H.S.,Risk Factors},
pages = {1365-1373},
volume = {51},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14511155},
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abstract = {OBJECTIVES: : To elucidate whether well-known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old. DESIGN: : A multidimensional survey of the Danish 1905 cohort conducted in 1998 with follow-up of vital status after 15 months. SETTING: : Denmark. PARTICIPANTS: : All Danes born in 1905, irrespective of physical and mental status were approached. Two thousand two hundred sixty-two persons of 3,600 participated in this survey. MEASUREMENTS: : Professional interviewers collected data concerning sociodemographic factors, smoking, alcohol consumption, body mass index, physical and cognitive performance, and health during a visit at the participant's residency. Cox regression models were used to evaluate predictors of mortality. RESULTS: : Five hundred seventy-nine (25.7%) of the 2,249 participants eligible for the analysis died during the 15 months follow-up. Multivariate analyses showed that marital status, education, smoking, obesity, consumption of alcohol, and number of self-reported diseases were not associated with mortality. Disability and cognitive impairment were significant risk factors in men and women. In addition poor self-rated health was associated with an increase in mortality in women. CONCLUSION: : In the oldest old, several known predictors of mortality, such as sociodemographic factors, smoking, and obesity, have lost their importance, but a high disability level, poor physical and cognitive performance, and self-rated health (women only), predict mortality, which shows that mortality in the oldest old is not a stochastic process.},
bibtype = {article},
author = {Nybo, H and Petersen, H C and Gaist, D and Jeune, B and Andersen, K and McGue, M and Vaupel, J W and Christensen, K},
journal = {J Am Geriatr Soc},
number = {10}
}Hereditary motor and sensory neuropathy with agenesis of the corpus callosum. Dupre, N., Howard, H., C., Mathieu, J., Karpati, G., Vanasse, M., Bouchard, J., P., Carpenter, S., & Rouleau, G., A. Ann Neurol, 54(1):9-18, 2003.
Paper abstract bibtex
Paper abstract bibtex Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.
@article{
title = {Hereditary motor and sensory neuropathy with agenesis of the corpus callosum},
type = {article},
year = {2003},
identifiers = {[object Object]},
keywords = {Adolescent,Adult,Atrophy/pathology,Brachial Plexus Neuritis/epidemiology,Brain/pathology,Child,Child, Preschool,Cognition Disorders/epidemiology,Comorbidity,Corpus Callosum/*abnormalities,Electromyography,Exons/genetics,Female,Gene Deletion,Genotype,Hereditary Motor and Sensory,Homozygote,Human,Infant,Infant, Newborn,Magnetic Resonance Imaging,Male,Median Nerve/physiopathology,Muscle Hypotonia/epidemiology,Neural Conduction/physiology,Neuropathies/epidemiology/*genetics/physiopatholog,Point Mutation/genetics,Quebec/epidemiology,Reflex, Abnormal/physiology,Support, Non-U.S. Gov't,Symporters/genetics},
pages = {9-18},
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notes = {<m:note>Journal Article<m:linebreak/>Review<m:linebreak/>Review of Reported Cases</m:note>},
abstract = {Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (OMIM 218000) is an autosomal recessive disease of early onset characterized by a delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, a variable degree of agenesis of the corpus callosum, amyotrophy, hypotonia, and cognitive impairment. Although this disorder has rarely been reported worldwide, it has a high prevalence in the Saguenay-Lac-St-Jean region of the province of Quebec (Canada) predominantly because of a founder effect. The gene defect responsible for this disorder recently has been identified, and it is a protein-truncating mutation in the SLC12A6 gene, which codes for a cotransporter protein known as KCC3. Herein, we provide the first extensive review of this disorder, covering epidemiological, clinical, and molecular genetic studies.},
bibtype = {article},
author = {Dupre, N and Howard, H C and Mathieu, J and Karpati, G and Vanasse, M and Bouchard, J P and Carpenter, S and Rouleau, G A},
journal = {Ann Neurol},
number = {1}
}The receptive fields of inferior temporal cortex neurons in natural scenes. Rolls, E. T, Aggelopoulos, N. C, & Zheng, F. J Neurosci, 23(1):339–348, 2003. Place: United States ISBN: 1529-2401
abstract bibtex
abstract bibtex
Inferior temporal cortex neurons have generally been found to have large visual receptive fields that typically include the fovea and extend throughout much of the visual field. However, a problem of such a large receptive field is that it does not easily support object selection by subsequent processing areas, in that all objects within such a large receptive field might activate inferior temporal cortex cells. To clarify this, we recorded from inferior temporal cortex neurons while macaques searched for objects in complex natural scenes or in plain backgrounds, as normally used. Inferior temporal cortex neuron receptive fields were much smaller in natural scenes (mean radius, 11 degrees) than in plain backgrounds (39 degrees). With two objects in a scene, one of which was a target for action (a touch), the firing rates were equally high during foveation of the effective stimulus when it was the target and when it was the distractor in both the plain and the complex scenes. With a plain background and two objects present, the receptive fields were much larger (24 degrees ) for the stimulus when it was the target than when it was the distractor (9 degrees ). This effect of object-based attention was much less evident in the complex scene, when the receptive fields were small both when the stimulus was a distractor and when it was a target. The results show that the temporal visual cortex provides an unambiguous representation in natural scenes by responding to the object shown at or close to the fixation point.
@article{rolls_receptive_2003,
title = {The receptive fields of inferior temporal cortex neurons in natural scenes.},
volume = {23},
abstract = {Inferior temporal cortex neurons have generally been found to have large visual receptive fields that typically include the fovea and extend throughout much of the visual field. However, a problem of such a large receptive field is that it does not easily support object selection by subsequent processing areas, in that all objects within such a large receptive field might activate inferior temporal cortex cells. To clarify this, we recorded from inferior temporal cortex neurons while macaques searched for objects in complex natural scenes or in plain backgrounds, as normally used. Inferior temporal cortex neuron receptive fields were much smaller in natural scenes (mean radius, 11 degrees) than in plain backgrounds (39 degrees). With two objects in a scene, one of which was a target for action (a touch), the firing rates were equally high during foveation of the effective stimulus when it was the target and when it was the distractor in both the plain and the complex scenes. With a plain background and two objects present, the receptive fields were much larger (24 degrees ) for the stimulus when it was the target than when it was the distractor (9 degrees ). This effect of object-based attention was much less evident in the complex scene, when the receptive fields were small both when the stimulus was a distractor and when it was a target. The results show that the temporal visual cortex provides an unambiguous representation in natural scenes by responding to the object shown at or close to the fixation point.},
language = {eng},
number = {1},
journal = {J Neurosci},
author = {Rolls, Edmund T and Aggelopoulos, Nicholas C and Zheng, Fashan},
year = {2003},
pmid = {12514233},
note = {Place: United States
ISBN: 1529-2401},
keywords = {Action Potentials, Animals, Kinetics, Macaca mulatta, Neurons, Visual Cortex, Visual Fields, Visual Perception, research support, non-u.s. gov't},
pages = {339--348},
}Association between BRCA1 mutations and ratio of female to male births in offspring of families with breast cancer, ovarian cancer, or both. de la Hoya, M., Fernandez, J., M., Tosar, A., Godino, J., Sanchez de Abajo, A., Vidart, J., A., Perez-Segura, P., Diaz-Rubio, E., Caldes, T., & Hoya, M., D. Jama, 290(7):929-931, 2003.
Paper abstract bibtex
Paper abstract bibtex CONTEXT: Defects in X-chromosome inactivation distort sex ratio in mice. The BRCA1 gene is also involved in X-chromosome inactivation, suggesting the possibility that some sex-ratio distortion may be associated with BRCA1-related human cancer syndromes. OBJECTIVE: To determine whether BRCA1 mutations are associated with distortion of the sex ratio of births in families with breast cancer, ovarian cancer, or both. DESIGN AND SETTING: Analysis of germline mutations in participants from Spain who had been screened for BRCA between 1998 and 2002. PARTICIPANTS: Sixty-eight families with at least 3 breast cancer cases or ovarian cancer cases, or both types of cancer in 2 generations (germline mutations: BRCA1, n = 17; BRCA2, n = 15; and BRCA unrelated, n = 36). An average of 4 relatives per family were tested for the corresponding BRCA mutation. MAIN OUTCOME MEASURE: Male and female births registered in breast and/or ovarian pedigrees tested for the presence of BRCA1 and BRCA2 germline mutations. RESULTS: Of BRCA1-related breast and/or ovarian cancer pedigrees, there was a 2-fold excess of female births (218 female vs 109 male births). Of BRCA2-related or BRCA-unrelated breast and/or ovarian cancer pedigrees, there was not an excess of female births (175 female/150 male and 344 female/315 male, respectively). Of 327 BRCA1 births, 218 (67%) were female births compared with 54% among BRCA2 pedigrees (175/327; P<.001) and 52% among BRCA-unrelated pedigrees (344/659; P<.001). Female births increased in the offspring of BRCA1 carriers compared with BRCA2 carriers (67% vs 52%; P =.004). CONCLUSION: In these families with breast and/or ovarian cancer, mutations in BRCA1 but not BRCA2 were associated with a sex ratio skewed against male births.
@article{
title = {Association between BRCA1 mutations and ratio of female to male births in offspring of families with breast cancer, ovarian cancer, or both},
type = {article},
year = {2003},
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pages = {929-931},
volume = {290},
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notes = {<m:note> <m:bold>From Duplicate 2 ( </m:bold> <m:bold> </m:bold><m:bold><m:italic>Association between BRCA1 mutations and ratio of female to male births in offspring of families with breast cancer, ovarian cancer, or both</m:italic></m:bold><m:bold> </m:bold> <m:bold> - de la Hoya, M; Fernandez, J M; Tosar, A; Godino, J; Sanchez de Abajo, A; Vidart, J A; Perez-Segura, P; Diaz-Rubio, E; Caldes, T )<m:linebreak/> </m:bold> <m:linebreak/>Journal Article<m:linebreak/> <m:linebreak/> </m:note>},
abstract = {CONTEXT: Defects in X-chromosome inactivation distort sex ratio in mice. The BRCA1 gene is also involved in X-chromosome inactivation, suggesting the possibility that some sex-ratio distortion may be associated with BRCA1-related human cancer syndromes. OBJECTIVE: To determine whether BRCA1 mutations are associated with distortion of the sex ratio of births in families with breast cancer, ovarian cancer, or both. DESIGN AND SETTING: Analysis of germline mutations in participants from Spain who had been screened for BRCA between 1998 and 2002. PARTICIPANTS: Sixty-eight families with at least 3 breast cancer cases or ovarian cancer cases, or both types of cancer in 2 generations (germline mutations: BRCA1, n = 17; BRCA2, n = 15; and BRCA unrelated, n = 36). An average of 4 relatives per family were tested for the corresponding BRCA mutation. MAIN OUTCOME MEASURE: Male and female births registered in breast and/or ovarian pedigrees tested for the presence of BRCA1 and BRCA2 germline mutations. RESULTS: Of BRCA1-related breast and/or ovarian cancer pedigrees, there was a 2-fold excess of female births (218 female vs 109 male births). Of BRCA2-related or BRCA-unrelated breast and/or ovarian cancer pedigrees, there was not an excess of female births (175 female/150 male and 344 female/315 male, respectively). Of 327 BRCA1 births, 218 (67%) were female births compared with 54% among BRCA2 pedigrees (175/327; P<.001) and 52% among BRCA-unrelated pedigrees (344/659; P<.001). Female births increased in the offspring of BRCA1 carriers compared with BRCA2 carriers (67% vs 52%; P =.004). CONCLUSION: In these families with breast and/or ovarian cancer, mutations in BRCA1 but not BRCA2 were associated with a sex ratio skewed against male births.},
bibtype = {article},
author = {de la Hoya, M and Fernandez, Juan M and Tosar, Alicia and Godino, Javier and Sanchez de Abajo, A and Vidart, J A and Perez-Segura, P and Diaz-Rubio, E and Caldes, T and Hoya, Miguel De},
journal = {Jama},
number = {7}
}Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan. Geesaman, B., J., Benson, E., Brewster, S., J., Kunkel, L., M., Blanche, H., Thomas, G., Perls, T., T., Daly, M., J., & Puca, A., A. Proc Natl Acad Sci U S A, 100(24):14115-14120, 2003.
Paper Website abstract bibtex
Paper Website abstract bibtex We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains approximately 50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy-Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity.
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title = {Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan},
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year = {2003},
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pages = {14115-14120},
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abstract = {We previously reported a genomewide linkage study for human longevity using 308 long-lived individuals (LLI) (centenarians or near-centenarians) in 137 sibships and identified statistically significant linkage within chromosome 4 near microsatellite D4S1564. This interval spans 12 million bp and contains approximately 50 putative genes. To identify the specific gene and gene variants impacting lifespan, we performed a haplotype-based fine-mapping study of the interval. The resulting genetic association study identified a haplotype marker within microsomal transfer protein as a modifier of human lifespan. This same variant was tested in a second cohort of LLI from France, and although the association was not replicated, there was evidence for statistical distortion in the form of Hardy-Weinberg disequilibrium. Microsomal transfer protein has been identified as the rate-limiting step in lipoprotein synthesis and may affect longevity by subtly modulating this pathway. This study provides proof of concept for the feasibility of using the genomes of LLI to identify genes impacting longevity.},
bibtype = {article},
author = {Geesaman, B J and Benson, E and Brewster, S J and Kunkel, L M and Blanche, H and Thomas, G and Perls, T T and Daly, M J and Puca, A A},
journal = {Proc Natl Acad Sci U S A},
number = {24}
}Y-chromosome evidence for differing ancient demographic histories in the Americas. Bortolini, M., C., Salzano, F., M., Thomas, M., G., Stuart, S., Nasanen, S., P., Bau, C., H., Hutz, M., H., Layrisse, Z., Petzl-Erler, M., L., Tsuneto, L., T., Hill, K., Hurtado, A., M., Castro-de-Guerra, D., Torres, M., M., Groot, H., Michalski, R., Nymadawa, P., Bedoya, G., Bradman, N., Labuda, D., & Ruiz-Linares, A. Am J Hum Genet, 73(3):524-539, 2003.
Paper abstract bibtex
Paper abstract bibtex To scrutinize the male ancestry of extant Native American populations, we examined eight biallelic and six microsatellite polymorphisms from the nonrecombining portion of the Y chromosome, in 438 individuals from 24 Native American populations (1 Na Dene and 23 South Amerinds) and in 404 Mongolians. One of the biallelic markers typed is a recently identified mutation (M242) characterizing a novel founder Native American haplogroup. The distribution, relatedness, and diversity of Y lineages in Native Americans indicate a differentiated male ancestry for populations from North and South America, strongly supporting a diverse demographic history for populations from these areas. These data are consistent with the occurrence of two major male migrations from southern/central Siberia to the Americas (with the second migration being restricted to North America) and a shared ancestry in central Asia for some of the initial migrants to Europe and the Americas. The microsatellite diversity and distribution of a Y lineage specific to South America (Q-M19) indicates that certain Amerind populations have been isolated since the initial colonization of the region, suggesting an early onset for tribalization of Native Americans. Age estimates based on Y-chromosome microsatellite diversity place the initial settlement of the American continent at approximately 14,000 years ago, in relative agreement with the age of well-established archaeological evidence.
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abstract = {To scrutinize the male ancestry of extant Native American populations, we examined eight biallelic and six microsatellite polymorphisms from the nonrecombining portion of the Y chromosome, in 438 individuals from 24 Native American populations (1 Na Dene and 23 South Amerinds) and in 404 Mongolians. One of the biallelic markers typed is a recently identified mutation (M242) characterizing a novel founder Native American haplogroup. The distribution, relatedness, and diversity of Y lineages in Native Americans indicate a differentiated male ancestry for populations from North and South America, strongly supporting a diverse demographic history for populations from these areas. These data are consistent with the occurrence of two major male migrations from southern/central Siberia to the Americas (with the second migration being restricted to North America) and a shared ancestry in central Asia for some of the initial migrants to Europe and the Americas. The microsatellite diversity and distribution of a Y lineage specific to South America (Q-M19) indicates that certain Amerind populations have been isolated since the initial colonization of the region, suggesting an early onset for tribalization of Native Americans. Age estimates based on Y-chromosome microsatellite diversity place the initial settlement of the American continent at approximately 14,000 years ago, in relative agreement with the age of well-established archaeological evidence.},
bibtype = {article},
author = {Bortolini, M C and Salzano, F M and Thomas, M G and Stuart, S and Nasanen, S P and Bau, C H and Hutz, M H and Layrisse, Z and Petzl-Erler, M L and Tsuneto, L T and Hill, K and Hurtado, A M and Castro-de-Guerra, D and Torres, M M and Groot, H and Michalski, R and Nymadawa, P and Bedoya, G and Bradman, N and Labuda, D and Ruiz-Linares, A},
journal = {Am J Hum Genet},
number = {3}
}2002 (9)
Building an Asynchronous Web-Based Tool for Machine Learning Classification. Weber, G., Vinterbo, S., & Ohno-Machado, L. JAMIA, Suppl. S:869–73, 2002.
abstract bibtex
abstract bibtex
Various unsupervised and supervised learning methods including support vector machines, classification trees, linear discriminant analysis and nearest neighbor classifiers have been used to classify high-throughput gene expression data. Simpler and more widely accepted statistical tools have not yet been used for this purpose, hence proper comparisons between classification methods have not been conducted. We developed free software that implements logistic regression with stepwise variable selection as a quick and simple method for initial exploration of important genetic markers in disease classification. To implement the algorithm and allow our collaborators in remote locations to evaluate and compare its results against those of other methods, we developed a user-friendly asynchronous web-based application with a minimal amount of programming using free, downloadable software tools. With this program, we show that classification using logistic regression can perform as well as other more sophisticated algorithms, and it has the advantages of being easy to interpret and reproduce. By making the tool freely and easily available, we hope to promote the comparison of classification methods. In addition, we believe our web application can be used as a model for other bioinformatics laboratories that need to develop web-based analysis tools in a short amount of time and on a limited budget.
@article{Weber2002,
title = {Building an Asynchronous Web-Based Tool for Machine Learning Classification.},
author = {Weber, Griffin and Vinterbo, Staal and {Ohno-Machado}, Lucila},
year = {2002},
journal = {JAMIA},
volume = {Suppl. S},
pages = {869--73},
abstract = {Various unsupervised and supervised learning methods including support vector machines, classification trees, linear discriminant analysis and nearest neighbor classifiers have been used to classify high-throughput gene expression data. Simpler and more widely accepted statistical tools have not yet been used for this purpose, hence proper comparisons between classification methods have not been conducted. We developed free software that implements logistic regression with stepwise variable selection as a quick and simple method for initial exploration of important genetic markers in disease classification. To implement the algorithm and allow our collaborators in remote locations to evaluate and compare its results against those of other methods, we developed a user-friendly asynchronous web-based application with a minimal amount of programming using free, downloadable software tools. With this program, we show that classification using logistic regression can perform as well as other more sophisticated algorithms, and it has the advantages of being easy to interpret and reproduce. By making the tool freely and easily available, we hope to promote the comparison of classification methods. In addition, we believe our web application can be used as a model for other bioinformatics laboratories that need to develop web-based analysis tools in a short amount of time and on a limited budget.},
copyright = {All rights reserved},
pii = {D020001919},
pubmedid = {12463949},
keywords = {12463949,Algorithms,Anonymous Testing,Artificial Intelligence,Carcinoma,Child,Comparative Study,Computerized,Confidentiality,Databases,Diagnosis,Differential,Disclosure,DNA,Gene Expression,Gene Expression Profiling,Gene Expression Regulation,Genetic Markers,Humans,Internet,Logistic Models,Lung Neoplasms,Medical Records Systems,Multivariate Analysis,Neoplasm,Neoplasms,Neoplastic,Neural Networks (Computer),Non-U.S. Gov't,Oligonucleotide Array Sequence Analysis,P.H.S.,Privacy,Research Support,Rhabdomyosarcoma,Sarcoma,Small Cell,Software,U.S. Gov't},
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}Comparing Imperfect Measurements with the Bland-Altman Technique: Application in Gene Expression Analysis. Ohno-Machado, L., Vinterbo, S., Dreiseitl, S., Jenssen, T., & Kuo, W. JAMIA, Suppl. S:572–6, 2002.
abstract bibtex
abstract bibtex
Several problems in medicine and biology involve the comparison of two measurements made on the same set of cases. The problem differs from a calibration problem because no gold standard can be identified. Testing the null hypothesis of no relationship using measures of association is not optimal since the measurements are made on the same cases, and therefore correlation coefficients will tend to be significant. The descriptive Bland-Altman method can be used in exploratory analysis of this problem, allowing the visualization of gross systematic differences between the two sets of measurements. We utilize the method on three sets of matched observations and demonstrate its usefulness in detecting systematic variations between two measurement technologies to assess gene expression.
@article{Ohno-Machado2002,
title = {Comparing Imperfect Measurements with the {{Bland-Altman}} Technique: Application in Gene Expression Analysis.},
author = {{Ohno-Machado}, Lucila and Vinterbo, Staal and Dreiseitl, Stephen and Jenssen, Tor-Kristian and Kuo, Winston},
year = {2002},
journal = {JAMIA},
volume = {Suppl. S},
pages = {572--6},
abstract = {Several problems in medicine and biology involve the comparison of two measurements made on the same set of cases. The problem differs from a calibration problem because no gold standard can be identified. Testing the null hypothesis of no relationship using measures of association is not optimal since the measurements are made on the same cases, and therefore correlation coefficients will tend to be significant. The descriptive Bland-Altman method can be used in exploratory analysis of this problem, allowing the visualization of gross systematic differences between the two sets of measurements. We utilize the method on three sets of matched observations and demonstrate its usefulness in detecting systematic variations between two measurement technologies to assess gene expression.},
copyright = {All rights reserved},
pii = {1833},
pubmedid = {12463888},
keywords = {12463888,Algorithms,Anonymous Testing,Artificial Intelligence,Bias (Epidemiology),Carcinoma,Child,Comparative Study,Computational Biology,Computerized,Confidentiality,Data Interpretation,Databases,Diagnosis,Differential,Disclosure,DNA,Gene Expression,Gene Expression Profiling,Gene Expression Regulation,Genetic Markers,Humans,Internet,Logistic Models,Lung Neoplasms,Medical Records Systems,Messenger,Multivariate Analysis,Neoplasm,Neoplasms,Neoplastic,Neural Networks (Computer),Non-U.S. Gov't,Oligonucleotide Array Sequence Analysis,P.H.S.,Privacy,Research Support,Rhabdomyosarcoma,RNA,Sarcoma,Small Cell,Software,Statistical,U.S. Gov't}
}Fine-scale mapping of disease loci via shattered coalescent modeling of genealogies. Morris, A., P., Whittaker, J., C., & Balding, D., J. Am J Hum Genet, 70(3):686-707., 2002.
Paper abstract bibtex
Paper abstract bibtex We present a Bayesian, Markov-chain Monte Carlo method for fine-scale linkage-disequilibrium gene mapping using high-density marker maps. The method explicitly models the genealogy underlying a sample of case chromosomes in the vicinity of a putative disease locus, in contrast with the assumption of a star-shaped tree made by many existing multipoint methods. Within this modeling framework, we can allow for missing marker information and for uncertainty about the true underlying genealogy and the makeup of ancestral marker haplotypes. A crucial advantage of our method is the incorporation of the shattered coalescent model for genealogies, allowing for multiple founding mutations at the disease locus and for sporadic cases of disease. Output from the method includes approximate posterior distributions of the location of the disease locus and population-marker haplotype proportions. In addition, output from the algorithm is used to construct a cladogram to represent genetic heterogeneity at the disease locus, highlighting clusters of case chromosomes sharing the same mutation. We present detailed simulations to provide evidence of improvements over existing methodology. Furthermore, inferences about the location of the disease locus are shown to remain robust to modeling assumptions.
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pages = {686-707.},
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abstract = {We present a Bayesian, Markov-chain Monte Carlo method for fine-scale linkage-disequilibrium gene mapping using high-density marker maps. The method explicitly models the genealogy underlying a sample of case chromosomes in the vicinity of a putative disease locus, in contrast with the assumption of a star-shaped tree made by many existing multipoint methods. Within this modeling framework, we can allow for missing marker information and for uncertainty about the true underlying genealogy and the makeup of ancestral marker haplotypes. A crucial advantage of our method is the incorporation of the shattered coalescent model for genealogies, allowing for multiple founding mutations at the disease locus and for sporadic cases of disease. Output from the method includes approximate posterior distributions of the location of the disease locus and population-marker haplotype proportions. In addition, output from the algorithm is used to construct a cladogram to represent genetic heterogeneity at the disease locus, highlighting clusters of case chromosomes sharing the same mutation. We present detailed simulations to provide evidence of improvements over existing methodology. Furthermore, inferences about the location of the disease locus are shown to remain robust to modeling assumptions.},
bibtype = {article},
author = {Morris, A P and Whittaker, J C and Balding, D J},
journal = {Am J Hum Genet},
number = {3}
}Do children of long-lived parents age more successfully?. Frederiksen, H., McGue, M., Jeune, B., Gaist, D., Nybo, H., Skytthe, A., Vaupel, J., W., & Christensen, K. Epidemiology, 13(3):334-339, 2002.
Website abstract bibtex
Website abstract bibtex BACKGROUND: Long-lived individuals are rare and may be selected in part for the genetic factors that promote successful aging. The children of long-lived parents may therefore age more successfully than the children of short-lived parents. METHODS: We used three major cross-sectional population-based surveys to study the association of parental longevity with successful aging in offspring. The measures of aging were hand-grip strength, cognitive performance (Mini Mental State Examination and a cognitive composite score), self-reported diseases, and self-rated health. RESULTS: For every additional 10 years the parents lived, their children's grip strength increased by 0.32 kg (95% CI = 0.00-0.63), Mini Mental State Examination score by 0.20 points (95% CI = 0.03-0.37), and cognitive composite score by 0.24 points (95% CI = 0.07-0.40). A 10-year increment of parental life was associated with a reduction by approximately 0.20 in the adjusted odds ratio for their children having each of the following conditions: diabetes; hypertension; ischemic heart disease; heart failure; stroke; or fair, poor, or very poor self-rated health. Almost all the effects were seen solely in the cohort of 70+-year-olds, but not among middle-aged or nonagenarian subjects. CONCLUSIONS: Parental life span is positively associated with the children's physical and cognitive functioning and avoidance of some of the common chronic diseases. However, the effects are small and are seen among offspring who are elderly, but not among the middle-aged or the oldest old.
@article{
title = {Do children of long-lived parents age more successfully?},
type = {article},
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pages = {334-339},
volume = {13},
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notes = {<m:note>1044-3983<m:linebreak/>Journal Article<m:linebreak/>Meta-Analysis</m:note>},
abstract = {BACKGROUND: Long-lived individuals are rare and may be selected in part for the genetic factors that promote successful aging. The children of long-lived parents may therefore age more successfully than the children of short-lived parents. METHODS: We used three major cross-sectional population-based surveys to study the association of parental longevity with successful aging in offspring. The measures of aging were hand-grip strength, cognitive performance (Mini Mental State Examination and a cognitive composite score), self-reported diseases, and self-rated health. RESULTS: For every additional 10 years the parents lived, their children's grip strength increased by 0.32 kg (95% CI = 0.00-0.63), Mini Mental State Examination score by 0.20 points (95% CI = 0.03-0.37), and cognitive composite score by 0.24 points (95% CI = 0.07-0.40). A 10-year increment of parental life was associated with a reduction by approximately 0.20 in the adjusted odds ratio for their children having each of the following conditions: diabetes; hypertension; ischemic heart disease; heart failure; stroke; or fair, poor, or very poor self-rated health. Almost all the effects were seen solely in the cohort of 70+-year-olds, but not among middle-aged or nonagenarian subjects. CONCLUSIONS: Parental life span is positively associated with the children's physical and cognitive functioning and avoidance of some of the common chronic diseases. However, the effects are small and are seen among offspring who are elderly, but not among the middle-aged or the oldest old.},
bibtype = {article},
author = {Frederiksen, H and McGue, M and Jeune, B and Gaist, D and Nybo, H and Skytthe, A and Vaupel, J W and Christensen, K},
journal = {Epidemiology},
number = {3}
}CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure. Vermeire, S., Wild, G., Kocher, K., Cousineau, J., Dufresne, L., Bitton, A., Langelier, D., Pare, P., Lapointe, G., Cohen, A., Daly, M., J., & Rioux, J., D. Am J Hum Genet, 71(1):74-83, 2002.
Paper Website abstract bibtex
Paper Website abstract bibtex The caspase recruitment domain gene (CARD15) was recently identified as the underlying gene associated with the IBD1 locus that confers susceptibility to Crohn disease (CD). CARD15 is related to the NOD1/Apaf-1 family of apoptosis regulators, and three sequence variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) in the gene were demonstrated to be associated with CD. We collected a cohort of 231 patients with CD and 71 healthy control individuals from the Canadian province of Quebec, to determine the prevalence of these sequence variants in an independent population. Clinical records of all patients were systematically reviewed, and detailed phenotypic information was obtained. All patient DNA samples were genotyped for the three variants, thus enabling an analysis of genotype-phenotype correlations. In this cohort, 45.0% of patients with CD carried at least one variant in the CARD15 gene, compared with 9.0% of control individuals (P<10-7). Allele frequencies of Arg702Trp, Gly908Arg, and Leu1007fsinsC were 12.9%, 5.2%, and 10.3% in patients with CD, compared with 4.2%, 0.7%, and 0.7% in control individuals, respectively. Importantly, CARD15 mutants were seen with equal frequency in patients with familial and sporadic CD. Analysis of the relationship between genotype and phenotype convincingly demonstrates that CARD15 variants are significantly associated with ileal disease involvement, as opposed to strictly colonic disease (P<.001). Moreover, we were able to determine the haplotype structure surrounding this disease gene by genotyping 45 single-nucleotide polymorphisms (SNPs) in a 177-kb region that contained the CARD15 gene. This structure helps clarify the history of these causal mutations. Finally, this analysis shows that CARD15 involvement with CD is detectable by use of publicly available SNPs alone.
@article{
title = {CARD15 genetic variation in a Quebec population: prevalence, genotype-phenotype relationship, and haplotype structure},
type = {article},
year = {2002},
identifiers = {[object Object]},
keywords = {*Intracellular Signaling Peptides and Proteins,*Variation (Genetics),Adult,Alleles,Base Sequence,Carrier Proteins/*genetics,Case-Control Studies,Cohort Studies,Crohn Disease/*genetics,DNA/genetics,Female,Gene Frequency,Genotype,Haplotypes,Humans,Male,Molecular Sequence Data,Mutation,Phenotype,Polymorphism, Single Nucleotide,Quebec,Research Support, Non-U.S. Gov't},
pages = {74-83},
volume = {71},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12019468},
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notes = {<m:note>0002-9297<m:linebreak/>Journal Article</m:note>},
abstract = {The caspase recruitment domain gene (CARD15) was recently identified as the underlying gene associated with the IBD1 locus that confers susceptibility to Crohn disease (CD). CARD15 is related to the NOD1/Apaf-1 family of apoptosis regulators, and three sequence variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) in the gene were demonstrated to be associated with CD. We collected a cohort of 231 patients with CD and 71 healthy control individuals from the Canadian province of Quebec, to determine the prevalence of these sequence variants in an independent population. Clinical records of all patients were systematically reviewed, and detailed phenotypic information was obtained. All patient DNA samples were genotyped for the three variants, thus enabling an analysis of genotype-phenotype correlations. In this cohort, 45.0% of patients with CD carried at least one variant in the CARD15 gene, compared with 9.0% of control individuals (P<10-7). Allele frequencies of Arg702Trp, Gly908Arg, and Leu1007fsinsC were 12.9%, 5.2%, and 10.3% in patients with CD, compared with 4.2%, 0.7%, and 0.7% in control individuals, respectively. Importantly, CARD15 mutants were seen with equal frequency in patients with familial and sporadic CD. Analysis of the relationship between genotype and phenotype convincingly demonstrates that CARD15 variants are significantly associated with ileal disease involvement, as opposed to strictly colonic disease (P<.001). Moreover, we were able to determine the haplotype structure surrounding this disease gene by genotyping 45 single-nucleotide polymorphisms (SNPs) in a 177-kb region that contained the CARD15 gene. This structure helps clarify the history of these causal mutations. Finally, this analysis shows that CARD15 involvement with CD is detectable by use of publicly available SNPs alone.},
bibtype = {article},
author = {Vermeire, S and Wild, G and Kocher, K and Cousineau, J and Dufresne, L and Bitton, A and Langelier, D and Pare, P and Lapointe, G and Cohen, A and Daly, M J and Rioux, J D},
journal = {Am J Hum Genet},
number = {1}
}A GENE-EXPRESSION SIGNATURE AS A PREDICTOR OF SURVIVAL IN BREAST CANCER. Vijver, M., J., V., d., Yudong, D., Veer, L., J., V., Dai, H., & Hart, A., A. The New England Journal of Medecine, 347(25):1999-2009, 2002.
Paper abstract bibtex
Paper abstract bibtex BACKGROUND: A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. METHODS: Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. RESULTS: Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome. CONCLUSIONS: The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.
@article{
title = {A GENE-EXPRESSION SIGNATURE AS A PREDICTOR OF SURVIVAL IN BREAST CANCER},
type = {article},
year = {2002},
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pages = {1999-2009},
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read = {false},
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notes = {<m:note> <m:bold>From Duplicate 2 ( </m:bold> <m:bold> </m:bold><m:bold><m:italic>A gene-expression signature as a predictor of survival in breast cancer</m:italic></m:bold><m:bold> </m:bold> <m:bold> - van de Vijver, M J; He, Y D; van't Veer, L J; Dai, H; Hart, A A; Voskuil, D W; Schreiber, G J; Peterse, J L; Roberts, C; Marton, M J; Parrish, M; Atsma, D; Witteveen, A; Glas, A; Delahaye, L; van der Velde, T; Bartelink, H; Rodenhuis, S; Rutgers, E T; Friend, S H; Bernards, R )<m:linebreak/> </m:bold> <m:linebreak/>Evaluation Studies<m:linebreak/>Journal Article<m:linebreak/> <m:linebreak/> </m:note>},
abstract = {BACKGROUND: A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy. METHODS: Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses. RESULTS: Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome. CONCLUSIONS: The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.},
bibtype = {article},
author = {Vijver, Marc J. Van de and Yudong, D. and Veer, Laura J. Van't and Dai, Hongyue and Hart, Augustinus A.M.},
journal = {The New England Journal of Medecine},
number = {25}
}Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing. Hoya, M., D., l., Osorio, A., Godino, J., Sulleiro, S., Tosar, A., Perez-Segura, P., Fernandez, C., de la Hoya, M., Rodriguez, R., Diaz-Rubio, E., Benitez, J., Devilee, P., & Caldes, T. Int J Cancer, 97(4):466-471, 2002.
Paper abstract bibtex
Paper abstract bibtex Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1-related families. Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer, concomitant breast/ovarian cancer in a single patient and prostate cancer but not unilateral breast cancer were associated with BRCA1 and BRCA2 mutations. Male breast cancer was associated with BRCA2 mutations. The presence of male breast cancer was the only cancer phenotype that distinguished BRCA2- from BRCA1-related families. We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics.
@article{
title = {Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing},
type = {article},
year = {2002},
identifiers = {[object Object]},
keywords = {*Genes,*Genetic Screening/economics,*Mutation,Age of Onset,Breast Neoplasms,Breast Neoplasms/epidemiology/*genetics,Cohort Studies,Comparative Study,Cost-Benefit Analysis,DNA,DNA Mutational Analysis,Exons/genetics,Female,Frameshift Mutation,Gene Frequency,Genetic Predisposition to Disease,Hereditary/epidemiology/*gen,Human,Male,Male/epidemiology/*genetics,Neoplasm/genetics,Neoplastic Syndromes,Non-U.S. Gov't,Ovarian Neoplasms/epidemiology/genetics,Portugal/epidemiology,Prevalence,RNA Splicing/genetics,Sequence Deletion,Spain/epidemiology,Support,brca1,brca2,characterising the complete spectrum,fami-,in a sufficient number,is best done by,kind are limited and,lies,logistic regression model,of mutations,of phenotypically fully characterised,probabilistic models of this,restricted},
pages = {466-471},
volume = {97},
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notes = {<m:note> <m:bold>From Duplicate 1 ( </m:bold> <m:bold> </m:bold><m:bold><m:italic>Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing</m:italic></m:bold><m:bold> </m:bold> <m:bold> - de la Hoya, M; Osorio, A; Godino, J; Sulleiro, S; Tosar, A; Perez-Segura, P; Fernandez, C; Rodriguez, R; Diaz-Rubio, E; Benitez, J; Devilee, P; Caldes, T )<m:linebreak/> </m:bold> <m:linebreak/>eng<m:linebreak/>Journal Article<m:linebreak/> <m:linebreak/> </m:note>},
abstract = {Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1-related families. Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer, concomitant breast/ovarian cancer in a single patient and prostate cancer but not unilateral breast cancer were associated with BRCA1 and BRCA2 mutations. Male breast cancer was associated with BRCA2 mutations. The presence of male breast cancer was the only cancer phenotype that distinguished BRCA2- from BRCA1-related families. We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics.},
bibtype = {article},
author = {Hoya, Miguel De la and Osorio, Ana and Godino, Javier and Sulleiro, Sara and Tosar, Alicia and Perez-Segura, Pedro and Fernandez, Christina and de la Hoya, M and Rodriguez, R and Diaz-Rubio, E and Benitez, J and Devilee, P and Caldes, T},
journal = {Int J Cancer},
number = {4}
}Detecting recombination in TT virus: a phylogenetic approach. Manni, F., Rotola, A., Caselli, E., Bertorelle, G., & Di Luca, D. J Mol Evol, 55(5):563-572, 2002.
Paper abstract bibtex
Paper abstract bibtex TT virus (TTV) has a remarkable genetic heterogeneity. To study TTV evolution, phylogenetic analyses were performed on 739 DNA sequences mapping in the N22 region of ORF1. Analysis of neighbor-joining consensus trees shows significant differences between DNA and protein phylogeny. Median joining networks phylogenetic clustering indicates that DNA sequence analysis is biased by homoplasy (i.e., genetic variability not originated by descent), indicative of either hypermutation or recombination. Statistical analysis shows that the significant excess of homoplasy is due to frequent recombination among closely related strains. Recombination events imply that the transmission of TTV is not clonal and provide the necessary basis to explain (i) the high degree of genetic divergence between TTV isolates, (ii) the lack of population structure on a world scale, and (iii) the number of highly divergent strains that seems typical of this virus. We show that recombination phenomena can be detected by phylogenetic analyses in very short sequences when a sufficiently large data set is available.
@article{
title = {Detecting recombination in TT virus: a phylogenetic approach},
type = {article},
year = {2002},
identifiers = {[object Object]},
keywords = {*Phylogeny,*Recombination, Genetic,DNA, Viral/genetics,Evolution, Molecular,Support, Non-U.S. Gov't,Transfusion-Transmitted Virus/*genetics,Variation (Genetics),Viral Proteins/genetics},
pages = {563-572},
volume = {55},
id = {07b0de60-3014-3ec3-b731-f0bdc6769cc5},
created = {2017-06-19T13:44:32.858Z},
file_attached = {true},
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tags = {03/05/15},
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starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>Journal Article</m:note>},
abstract = {TT virus (TTV) has a remarkable genetic heterogeneity. To study TTV evolution, phylogenetic analyses were performed on 739 DNA sequences mapping in the N22 region of ORF1. Analysis of neighbor-joining consensus trees shows significant differences between DNA and protein phylogeny. Median joining networks phylogenetic clustering indicates that DNA sequence analysis is biased by homoplasy (i.e., genetic variability not originated by descent), indicative of either hypermutation or recombination. Statistical analysis shows that the significant excess of homoplasy is due to frequent recombination among closely related strains. Recombination events imply that the transmission of TTV is not clonal and provide the necessary basis to explain (i) the high degree of genetic divergence between TTV isolates, (ii) the lack of population structure on a world scale, and (iii) the number of highly divergent strains that seems typical of this virus. We show that recombination phenomena can be detected by phylogenetic analyses in very short sequences when a sufficiently large data set is available.},
bibtype = {article},
author = {Manni, F and Rotola, A and Caselli, E and Bertorelle, G and Di Luca, D},
journal = {J Mol Evol},
number = {5}
}Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa. Le Saux, O., Beck, K., Sachsinger, C., Treiber, C., Goring, H., H., Curry, K., Johnson, E., W., Bercovitch, L., Marais, A., S., Terry, S., F., Viljoen, D., L., & Boyd, C., D. Hum Genet, 111(4-5):331-8., 2002.
abstract bibtex
abstract bibtex
Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners. A previous report has suggested that a founder effect may explain the higher prevalence of PXE in Afrikaners, a European-derived population that first settled in South Africa in the 17th century. To investigate this hypothesis, we performed haplotype and mutational analysis of DNA from 24 South African families of Afrikaner, British and Indian descent. Among the 17 Afrikaner families studied, three common haplotypes and six different disease-causing variants were identified. Three of these mutant alleles were missense variants, two were nonsense mutations and one was a single base-pair insertion. The most common variant accounted for 53% of the PXE alleles, whereas other mutant alleles appeared at lower frequencies ranging from 3% to 12%. Haplotype analysis of the Afrikaner families showed that the three most frequent mutations were identical-by-descent, indicating a founder origin of PXE in this population.
@article{
title = {Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa},
type = {article},
year = {2002},
identifiers = {[object Object]},
keywords = {*Founder Effect,*Genetics, Population,Haplotypes,Human,Molecular Sequence Data,Multidrug Resistance-Associated Proteins/genetics,Mutation,Pedigree,Prevalence,Pseudoxanthoma Elasticum/epidemiology/ethnology/*g,South Africa/epidemiology,Support, Non-U.S. Gov't,Support, U.S. Gov't, P.H.S.},
pages = {331-8.},
volume = {111},
id = {f9c39121-c1f6-3af6-9370-5ac65c1d3a3f},
created = {2017-06-19T13:45:55.928Z},
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tags = {03/01/08},
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authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {Pseudoxanthoma elasticum (PXE) is a heritable elastic tissue disorder recently shown to be attributable to mutations in the ABCC6 ( MRP6) gene. Whereas PXE has been identified in all ethnic groups studied to date, the prevalence of this disease in various populations is uncertain, although often assumed to be similar. A notable exception however is the prevalence of PXE among South African Afrikaners. A previous report has suggested that a founder effect may explain the higher prevalence of PXE in Afrikaners, a European-derived population that first settled in South Africa in the 17th century. To investigate this hypothesis, we performed haplotype and mutational analysis of DNA from 24 South African families of Afrikaner, British and Indian descent. Among the 17 Afrikaner families studied, three common haplotypes and six different disease-causing variants were identified. Three of these mutant alleles were missense variants, two were nonsense mutations and one was a single base-pair insertion. The most common variant accounted for 53% of the PXE alleles, whereas other mutant alleles appeared at lower frequencies ranging from 3% to 12%. Haplotype analysis of the Afrikaner families showed that the three most frequent mutations were identical-by-descent, indicating a founder origin of PXE in this population.},
bibtype = {article},
author = {Le Saux, O and Beck, K and Sachsinger, C and Treiber, C and Goring, H H and Curry, K and Johnson, E W and Bercovitch, L and Marais, A S and Terry, S F and Viljoen, D L and Boyd, C D},
journal = {Hum Genet},
number = {4-5}
}2001 (16)
Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation. Fuster, V., Jimenez, A., M., & Colantonio, S., E. Hum Biol, 73(2):249-70., 2001.
Paper abstract bibtex
Paper abstract bibtex The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tietar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tietar) are interpreted considering the geography, population size, and population mobility for each valley
@article{
title = {Inbreeding in Gredos mountain range (Spain): contribution of multiple consanguinity and intervalley variation},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Consanguinity,Ethnic Groups/*genetics,Geography,Human,Probability,Socioeconomic Factors,Spain,Support, Non-U.S. Gov't,Time Factors},
pages = {249-70.},
volume = {73},
id = {cbd6acf1-d154-3cbf-8680-aafc30f04c2c},
created = {2017-06-19T13:42:23.243Z},
file_attached = {true},
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group_id = {b2078731-0913-33b9-8902-a53629a24e83},
last_modified = {2017-06-19T13:42:23.412Z},
tags = {02/02/13},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {The present paper examines consanguineous marriages occurring between 1874 and 1975 in three valleys (Tormes, Alberche, and Tietar) in the Sierra de Gredos mountain range, Avila province, Spain. Information was obtained from parish registers of 42 localities, corresponding to a total of 41,696 weddings. Consanguineous marriages were defined as those up to the third degree of consanguinity (second cousins). From 1874 to 1975 the percentage of related mates was 4.45% and the inbreeding coefficient was 0.0011868 (for 1874 to 1917 corresponding figures up to the fourth degree were 16.44% and 0.00 19085, respectively). In order to ascertain the characteristics and evolution of mating patterns in Gredos, the contribution of each degree of kinship was analyzed as a whole and then for each valley separately. Regarding total consanguineous marriages in Gredos, there is a low frequency of uncle-niece matings (0.21%) and a first-second cousin mating ratio (C22/C33) of 0.23 (up to the third degree of consanguinity). Before 1918 multiple matings (i.e., those involving more than a single relationship) accounted for 19.16% of consanguineous marriages (up to the fourth degree). The observed frequencies of multiple consanguineous marriages was, on average, about twice that expected at random, and the proportion of such marriages to total inbreeding was 34.65%. The temporal change of the Gredos inbreeding pattern was characterized by a recent decrease; the highest inbreeding levels correspond to the period from 1915 to 1944. Finally, intervalley differences (maximum inbreeding coefficient in the Tormes, minimum in the Tietar) are interpreted considering the geography, population size, and population mobility for each valley},
bibtype = {article},
author = {Fuster, V and Jimenez, A M and Colantonio, S E},
journal = {Hum Biol},
number = {2}
}Differences in disease frequency between Europeans and Polynesians: directions for future research into genetic risk factors. Abbott, W., Scragg, R., & Marbrook, J. Pac Health Dialog, 8(1):129-56., 2001.
abstract bibtex
abstract bibtex
The purpose of this review is to identify complex genetic diseases that might be common in Polynesian ethnic groups because of a high frequency of susceptibility genes. Since a number of Polynesian ethnic groups are descended from recent founder populations, they may be especially suitable for studies designed to identify these genes. We have reviewed the epidemiological literature looking for diseases that i) have a higher frequency in at least two Polynesian groups than in Europeans living in the same geographic areas, ii) are not at high frequency in Polynesia entirely because of high levels of known environmental risk factors, and iii) are known to be inherited in other ethnic groups. Twenty-one diseases fulfilling these three criteria were identified. It may be possible to design studies to identify the genes that cause these diseases in Polynesian ethnic groups.
@article{
title = {Differences in disease frequency between Europeans and Polynesians: directions for future research into genetic risk factors},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {Cardiovascular Diseases/epidemiology/ethnology/gen,Communicable Diseases/epidemiology/ethnology/genet,Comparative Study,Cross-Sectional Studies,Ethnic Groups/*genetics,Europe,Female,Genetic Predisposition to Disease/*ethnology,Human,Male,Mental Disorders/epidemiology/ethnology/genetics,Neoplasms/epidemiology/ethnology/genetics,Polynesia,Respiratory Tract Infections/epidemiology/ethnolog,Risk Factors,Support, Non-U.S. Gov't},
pages = {129-56.},
volume = {8},
id = {d2b1e45e-388c-3f80-aade-5bb60895ae60},
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notes = {<m:note>eng<m:linebreak/>Journal Article<m:linebreak/>Review<m:linebreak/>Review, Academic</m:note>},
abstract = {The purpose of this review is to identify complex genetic diseases that might be common in Polynesian ethnic groups because of a high frequency of susceptibility genes. Since a number of Polynesian ethnic groups are descended from recent founder populations, they may be especially suitable for studies designed to identify these genes. We have reviewed the epidemiological literature looking for diseases that i) have a higher frequency in at least two Polynesian groups than in Europeans living in the same geographic areas, ii) are not at high frequency in Polynesia entirely because of high levels of known environmental risk factors, and iii) are known to be inherited in other ethnic groups. Twenty-one diseases fulfilling these three criteria were identified. It may be possible to design studies to identify the genes that cause these diseases in Polynesian ethnic groups.},
bibtype = {article},
author = {Abbott, W and Scragg, R and Marbrook, J},
journal = {Pac Health Dialog},
number = {1}
}After BRCA1 and BRCA2-what next? Multifactorial segregation analyses of three-generation, population-based Australian families affected by female breast cancer. Cui, J., Antoniou, A., C., Dite, G., S., Southey, M., C., Venter, D., J., Easton, D., F., Giles, G., G., McCredie, M., R., & Hopper, J., L. Am J Hum Genet, 68(2):420-31., 2001.
Paper abstract bibtex
Paper abstract bibtex Mutations in BRCA1 and BRCA2 that cause a dominantly inherited high risk of female breast cancer seem to explain only a small proportion of the aggregation of the disease. To study the possible additional genetic components, we conducted single-locus and two-locus segregation analyses, with and without a polygenic background, using three-generation families ascertained through 858 women with breast cancer diagnosed at age <40 years, ascertained through population cancer registries in Melbourne and Sydney, Australia. Extensive testing for deleterious mutations in BRCA1 and BRCA2, to date, has identified 34 carriers. Our analysis suggested that, after other possible unmeasured familial factors are adjusted for and the known BRCA1 and BRCA2 mutation carriers are excluded, there appears to be a residual dominantly inherited risk of female breast cancer in addition to that derived from mutations in BRCA1 and BRCA2. This study also suggests that there is a substantial recessively inherited risk of early-onset breast cancer. According to the best-fitting model, after excluding known carriers of mutations in BRCA1 and BRCA2, about 1/250 (95% confidence interval [CI] 1/500 to 1/125) women have a recessive risk of 86% (95% CI 69%-100%) by age 50 years and of almost 100% by age 60 years. Possible reasons that our study has implicated a novel strong recessive effect include our inclusion of data on lineal aunts and grandmothers, study of families ascertained through women with early-onset breast cancer, allowance for multiple familial factors in the analysis, and removal of families for whom the cause (i.e., BRCA1 or BRCA2) is known. Our findings may have implications for attempts to identify new breast cancer-susceptibility genes.
@article{
title = {After BRCA1 and BRCA2-what next? Multifactorial segregation analyses of three-generation, population-based Australian families affected by female breast cancer},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {Age Factors,Age of Onset,Australia,BRCA1 Protein/*genetics,BRCA2 Protein,Breast Neoplasms/*genetics,Cohort Studies,Family Health,Female,Heterozygote,Human,Male,Models, Genetic,Molecular Sequence Data,Mutation,Neoplasm Proteins/*genetics,Pedigree,Probability,Risk Factors,Statistics,Support, Non-U.S. Gov't,Support, U.S. Gov't, P.H.S.,Transcription Factors/*genetics},
pages = {420-31.},
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abstract = {Mutations in BRCA1 and BRCA2 that cause a dominantly inherited high risk of female breast cancer seem to explain only a small proportion of the aggregation of the disease. To study the possible additional genetic components, we conducted single-locus and two-locus segregation analyses, with and without a polygenic background, using three-generation families ascertained through 858 women with breast cancer diagnosed at age <40 years, ascertained through population cancer registries in Melbourne and Sydney, Australia. Extensive testing for deleterious mutations in BRCA1 and BRCA2, to date, has identified 34 carriers. Our analysis suggested that, after other possible unmeasured familial factors are adjusted for and the known BRCA1 and BRCA2 mutation carriers are excluded, there appears to be a residual dominantly inherited risk of female breast cancer in addition to that derived from mutations in BRCA1 and BRCA2. This study also suggests that there is a substantial recessively inherited risk of early-onset breast cancer. According to the best-fitting model, after excluding known carriers of mutations in BRCA1 and BRCA2, about 1/250 (95% confidence interval [CI] 1/500 to 1/125) women have a recessive risk of 86% (95% CI 69%-100%) by age 50 years and of almost 100% by age 60 years. Possible reasons that our study has implicated a novel strong recessive effect include our inclusion of data on lineal aunts and grandmothers, study of families ascertained through women with early-onset breast cancer, allowance for multiple familial factors in the analysis, and removal of families for whom the cause (i.e., BRCA1 or BRCA2) is known. Our findings may have implications for attempts to identify new breast cancer-susceptibility genes.},
bibtype = {article},
author = {Cui, J and Antoniou, A C and Dite, G S and Southey, M C and Venter, D J and Easton, D F and Giles, G G and McCredie, M R and Hopper, J L},
journal = {Am J Hum Genet},
number = {2}
}Replication studies in longevity: puzzling findings in Danish centenarians at the 3'APOB-VNTR locus. Varcasia, O., Garasto, S., Rizza, T., Andersen-Ranberg, K., Jeune, B., Bathum, L., Andreev, K., Tan, Q., Yashin, A., I., Bonafe, M., Franceschi, C., & De Benedictis, G. Ann Hum Genet, 65(Pt 4):371-376, 2001.
Website abstract bibtex
Website abstract bibtex In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20-64-year-old subjects. However, when Danish and Italian data were compared, a significant difference (p = 0.0004) was found between the frequencies of Small alleles in youths, which disappeared in centenarians (p = 0.290). Furthermore, the demographic-genetic approach revealed in Danes a significant gene-sex interaction relevant to Long alleles (more than 37 repeats). The different findings in Denmark and Italy suggest that gene/longevity associations are population-specific, and heavily affected by the population-specific genetic and environmental history.
@article{
title = {Replication studies in longevity: puzzling findings in Danish centenarians at the 3'APOB-VNTR locus},
type = {article},
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pages = {371-376},
volume = {65},
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abstract = {In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20-64-year-old subjects. However, when Danish and Italian data were compared, a significant difference (p = 0.0004) was found between the frequencies of Small alleles in youths, which disappeared in centenarians (p = 0.290). Furthermore, the demographic-genetic approach revealed in Danes a significant gene-sex interaction relevant to Long alleles (more than 37 repeats). The different findings in Denmark and Italy suggest that gene/longevity associations are population-specific, and heavily affected by the population-specific genetic and environmental history.},
bibtype = {article},
author = {Varcasia, O and Garasto, S and Rizza, T and Andersen-Ranberg, K and Jeune, B and Bathum, L and Andreev, K and Tan, Q and Yashin, A I and Bonafe, M and Franceschi, C and De Benedictis, G},
journal = {Ann Hum Genet},
number = {Pt 4}
}Genetic structures and linguistic boundaries in Italy: a microregional approach. Manni, F. & Barrai, I. Hum Biol, 73(3):335-347, 2001.
Paper abstract bibtex
Paper abstract bibtex The amount of genetic data (sequences, gene frequencies, and isonymy) available for the Province of Ferrara, Italy, makes this area one of the world's best known. In an effort to infer the underlying demographic processes, we studied the province's population structure by comparing geological, palaeoclimatic, archeological, historical, and linguistic data. This multilevel approach allowed us to date some characteristics of the population structure from prehistoric times to the Roman and Middle Ages, and to detect overlapping biological, cultural, and geographic boundaries. To detect linguistic boundaries within this area we turned pronunciation differences into phonetic notation. We then computed pairwise distances by using methods for multiple genetic sequence analysis, in order to obtain a distance matrix of the overall pronunciation variability. This approach enabled us to test the association among linguistic, geographical, and genetic distance matrices using the same statistical tests. Results indicate that demographic phenomena can be traced in an area as small as the Province of Ferrara and that, on a microregional scale, recent events may have influenced important aspects of the overall genetic variation.
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title = {Genetic structures and linguistic boundaries in Italy: a microregional approach},
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pages = {335-347},
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abstract = {The amount of genetic data (sequences, gene frequencies, and isonymy) available for the Province of Ferrara, Italy, makes this area one of the world's best known. In an effort to infer the underlying demographic processes, we studied the province's population structure by comparing geological, palaeoclimatic, archeological, historical, and linguistic data. This multilevel approach allowed us to date some characteristics of the population structure from prehistoric times to the Roman and Middle Ages, and to detect overlapping biological, cultural, and geographic boundaries. To detect linguistic boundaries within this area we turned pronunciation differences into phonetic notation. We then computed pairwise distances by using methods for multiple genetic sequence analysis, in order to obtain a distance matrix of the overall pronunciation variability. This approach enabled us to test the association among linguistic, geographical, and genetic distance matrices using the same statistical tests. Results indicate that demographic phenomena can be traced in an area as small as the Province of Ferrara and that, on a microregional scale, recent events may have influenced important aspects of the overall genetic variation.},
bibtype = {article},
author = {Manni, F and Barrai, I},
journal = {Hum Biol},
number = {3}
}Objects and attention: The state of the art. Scholl, B. J. Cognition, 80(1-2):1-46, 2001.
abstract bibtex
abstract bibtex
What are the units of attention? In addition to standard models holding that attention can select spatial regions and visual features, recent work suggests that in some cases attention can directly select discrete objects. This paper reviews the state of the art with regard to such 'object-based' attention, and explores how objects of attention relate to locations, reference frames, perceptual groups, surfaces, parts, and features. Also discussed are the dynamic aspects of objecthood, including the question of how attended objects are individuated in time, and the possibility of attending to simple dynamic motions and events. The final sections of this review generalize these issues beyond vision science, to other modalities and fields such as auditory objects of attention and the infant's 'object concept'.
@Article{Scholl2001b,
author = {B. J. Scholl},
journal = {Cognition},
title = {Objects and attention: {T}he state of the art.},
year = {2001},
number = {1-2},
pages = {1-46},
volume = {80},
abstract = {What are the units of attention? In addition to standard models holding
that attention can select spatial regions and visual features, recent
work suggests that in some cases attention can directly select discrete
objects. This paper reviews the state of the art with regard to such
'object-based' attention, and explores how objects of attention relate
to locations, reference frames, perceptual groups, surfaces, parts,
and features. Also discussed are the dynamic aspects of objecthood,
including the question of how attended objects are individuated in
time, and the possibility of attending to simple dynamic motions
and events. The final sections of this review generalize these issues
beyond vision science, to other modalities and fields such as auditory
objects of attention and the infant's 'object concept'.},
keywords = {80 and over, Adenoviridae, Adolescent, Adult, Aged, Analysis of Variance, Animals, Attention, Auditory Perception, Biopsy, Bone Nails, Bone Neoplasms, Bone Screws, Bone Transplantation, Breast Neoplasms, Carcinoma, Child, Child Development, Cognition, Cohort Studies, Comparative Study, Concept Formation, Constriction, Esophageal Neoplasms, Female, Femoral Neck Fractures, Femoral Neoplasms, Femur Head, Femur Neck, Fibula, Follow-Up Studies, Fracture Fixation, Fractures, Gene Expression, Gene Transfer Techniques, Green Fluorescent Proteins, Hepatitis, Homologous, Humans, Inbred Strains, Infant, Injections, Internal, Intramedullary, Intravenous, Judgment, Knee Joint, Liver, Luminescent Proteins, Male, Meta-Analysis, Middle Aged, Models, Motion, Motion Perception, Needle, Neoplasms, Non-P.H.S., Non-U.S. Gov't, P.H.S., Perceptual Distortion, Portal Vein, Preschool, Problem Solving, Psychological, Radiation-Induced, Rats, Research Support, Retrospective Studies, Second Primary, Self Concept, Sensitivity and Specificity, Social Perception, Space Perception, Spontaneous, Squamous Cell, Students, Time Factors, Tomography, Transplantation, Treatment Outcome, U.S. Gov't, Visual Perception, X-Ray Computed, 11245838},
}Understanding human disease mutations through the use of interspecific genetic variation. Miller, M., P. & Kumar, S. Hum Mol Genet, 10(21):2319-2328, 2001.
Paper Website abstract bibtex
Paper Website abstract bibtex Data on replacement mutations in genes of disease patients exist in a variety of online resources. In addition, genome sequencing projects and individual gene sequencing efforts have led to the identification of disease gene homologs in diverse metazoan species. The availability of these two types of information provides unique opportunities to investigate factors that are important in the development of genetically based disease by contrasting long and short-term molecular evolutionary patterns. Therefore, we conducted an analysis of disease-associated human genetic variation for seven disease genes: the cystic fibrosis transmembrane conductance regulator, glucose-6-phosphate dehydrogenase, the neural cell adhesion molecule L1, phenylalanine hydroxylase, paired box 6, the X-linked retinoschisis gene and TSC2/tuberin. Our analyses indicate that disease mutations show definite patterns when examined from an evolutionary perspective. Human replacement mutations resulting in disease are overabundant at amino acid positions most conserved throughout the long-term history of metazoans. In contrast, human polymorphic replacement mutations and silent mutations are randomly distributed across sites with respect to the level of conservation of amino acid sites within genes. Furthermore, disease-causing amino acid changes are of types usually not observed among species. Using Grantham's chemical difference matrix, we find that amino acid changes observed in disease patients are far more radical than the variation found among species and in non-diseased humans. Overall, our results demonstrate the usefulness of evolutionary analyses for understanding patterns of human disease mutations and underscore the biomedical significance of sequence data currently being generated from various model organism genome sequencing projects.
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title = {Understanding human disease mutations through the use of interspecific genetic variation},
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pages = {2319-2328},
volume = {10},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689479},
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abstract = {Data on replacement mutations in genes of disease patients exist in a variety of online resources. In addition, genome sequencing projects and individual gene sequencing efforts have led to the identification of disease gene homologs in diverse metazoan species. The availability of these two types of information provides unique opportunities to investigate factors that are important in the development of genetically based disease by contrasting long and short-term molecular evolutionary patterns. Therefore, we conducted an analysis of disease-associated human genetic variation for seven disease genes: the cystic fibrosis transmembrane conductance regulator, glucose-6-phosphate dehydrogenase, the neural cell adhesion molecule L1, phenylalanine hydroxylase, paired box 6, the X-linked retinoschisis gene and TSC2/tuberin. Our analyses indicate that disease mutations show definite patterns when examined from an evolutionary perspective. Human replacement mutations resulting in disease are overabundant at amino acid positions most conserved throughout the long-term history of metazoans. In contrast, human polymorphic replacement mutations and silent mutations are randomly distributed across sites with respect to the level of conservation of amino acid sites within genes. Furthermore, disease-causing amino acid changes are of types usually not observed among species. Using Grantham's chemical difference matrix, we find that amino acid changes observed in disease patients are far more radical than the variation found among species and in non-diseased humans. Overall, our results demonstrate the usefulness of evolutionary analyses for understanding patterns of human disease mutations and underscore the biomedical significance of sequence data currently being generated from various model organism genome sequencing projects.},
bibtype = {article},
author = {Miller, M P and Kumar, S},
journal = {Hum Mol Genet},
number = {21}
}Increase of homozygosity in centenarians revealed by a new inter-Alu PCR technique. Bonafe, M., Cardelli, M., Marchegiani, F., Cavallone, L., Giovagnetti, S., Olivieri, F., Lisa, R., Pieri, C., & Franceschi, C. Exp Gerontol, 36(7):1063-1073, 2001.
Paper Website abstract bibtex
Paper Website abstract bibtex In the present study a novel inter-Alu PCR technique that allows one to detect inter-individual differences in the genomic regions flanked by Alu repetitive sequences was developed. Two primers complementary to sequences present in different Alu repeats and marked with two different fluorochromes were used in the same PCR reaction, and the PCR products were separated and analyzed by capillary electrophoresis using an automatic sequencer. The method is highly reliable, and three patterns of peaks (QM376-400, QM780-790 and QM480) appeared to be representative for germ-line polymorphisms, as suggested by the results obtained in nine couples of monozygotic twins and four three-generation families. The frequency of these polymorphic peaks was studied in two different age groups (100 young subjects and 69 centenarians). In two out of the three regions (QM376-400 and QM480) a significant increase in homozygote genotypes frequency was observed in centenarians. These counterintuitive results suggest that increased homozygosity contributes to human longevity. This novel inter-Alu PCR approach could represent a valuable tool to identify longevity-associated DNA sequences interspersed throughout human genome, without making any a priori assumption about their nature and function.
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title = {Increase of homozygosity in centenarians revealed by a new inter-Alu PCR technique},
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volume = {36},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11404051},
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abstract = {In the present study a novel inter-Alu PCR technique that allows one to detect inter-individual differences in the genomic regions flanked by Alu repetitive sequences was developed. Two primers complementary to sequences present in different Alu repeats and marked with two different fluorochromes were used in the same PCR reaction, and the PCR products were separated and analyzed by capillary electrophoresis using an automatic sequencer. The method is highly reliable, and three patterns of peaks (QM376-400, QM780-790 and QM480) appeared to be representative for germ-line polymorphisms, as suggested by the results obtained in nine couples of monozygotic twins and four three-generation families. The frequency of these polymorphic peaks was studied in two different age groups (100 young subjects and 69 centenarians). In two out of the three regions (QM376-400 and QM480) a significant increase in homozygote genotypes frequency was observed in centenarians. These counterintuitive results suggest that increased homozygosity contributes to human longevity. This novel inter-Alu PCR approach could represent a valuable tool to identify longevity-associated DNA sequences interspersed throughout human genome, without making any a priori assumption about their nature and function.},
bibtype = {article},
author = {Bonafe, M and Cardelli, M and Marchegiani, F and Cavallone, L and Giovagnetti, S and Olivieri, F and Lisa, R and Pieri, C and Franceschi, C},
journal = {Exp Gerontol},
number = {7}
}Prevalence of BRCA1 founder mutations in western Poland. Jasinska, A. & Krzyzosiak, W., J. Hum Mutat, 17(1):75., 2001.
abstract bibtex
abstract bibtex
The frequency of three BRCA1 founder mutations was examined in a group of Polish breast/ovarian cancer patients and women at increased risk of these cancers based on family history. Among the 15 mutations found (5385-5386insC, 187-188delAG, and 4154delA), eight were detected in women with a low or moderate family history. The frequency of the IVS20+48ins12 variant was also analyzed and its distribution within risk groups argues against its involvement in cancer predisposition.
@article{
title = {Prevalence of BRCA1 founder mutations in western Poland},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Founder Effect,Adult,Aged,Breast Neoplasms/epidemiology/genetics,Female,Genes, BRCA1/*genetics,Human,Middle Age,Mutation/*genetics,Ovarian Neoplasms/epidemiology/genetics,Poland/epidemiology,Prevalence,Support, Non-U.S. Gov't},
pages = {75.},
volume = {17},
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abstract = {The frequency of three BRCA1 founder mutations was examined in a group of Polish breast/ovarian cancer patients and women at increased risk of these cancers based on family history. Among the 15 mutations found (5385-5386insC, 187-188delAG, and 4154delA), eight were detected in women with a low or moderate family history. The frequency of the IVS20+48ins12 variant was also analyzed and its distribution within risk groups argues against its involvement in cancer predisposition.},
bibtype = {article},
author = {Jasinska, A and Krzyzosiak, W J},
journal = {Hum Mutat},
number = {1}
}BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients. Sarantaus, L., Vahteristo, P., Bloom, E., Tamminen, A., Unkila-Kallio, L., Butzow, R., & Nevanlinna, H. Eur J Hum Genet, 9(6):424-30., 2001.
abstract bibtex
abstract bibtex
Germline mutations of BRCA1 and BRCA2 predispose to hereditary breast-ovarian cancer syndrome. In Finland, 20 different BRCA1/2 mutations have been identified, and 13 of them are founder mutations that account for the vast majority of Finnish BRCA1/2 families. The purpose of our study was to determine the prevalence of BRCA1/2 mutations in unselected Finnish ovarian carcinoma patients and to evaluate the relationship between mutation carrier status and personal/family history of cancer. Two hundred and thirty-three patients were screened for all the 20 BRCA1/2 mutations known in the Finnish population. Additionally, a subgroup of patients with personal history of breast cancer and/or family history of breast and/or ovarian cancer was screened for novel BRCA1/2 mutations. Thirteen patients (5.6%) had mutations: eleven in BRCA1 and two in BRCA2. All the mutation-positive patients were carriers of the previously known Finnish BRCA1/2 mutations, and seven recurrent founder mutations accounted for 12 of the 13 mutations detected. A logistic regression analysis was used to determine the odds of mutation for ovarian carcinoma patients. The most significant predictor of a mutation was the presence of both breast and ovarian cancer in the same woman, but family history of breast cancer was also strongly related to mutation carrier status. Although BRCA1/2 mutation testing is not warranted in the general Finnish ovarian cancer patient population, patients who have also been diagnosed with breast cancer or have family history of breast or breast and ovarian cancer could benefit from referral to genetic counselling and mutation testing.
@article{
title = {BRCA1 and BRCA2 mutations among 233 unselected Finnish ovarian carcinoma patients},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Mutation,BRCA1 Protein/*genetics,Carcinoma/*genetics,Cohort Studies,Family Health,Female,Finland,Founder Effect,Human,Logistic Models,Neoplasm Proteins/*genetics,Ovarian Neoplasms/epidemiology/*genetics,Support, Non-U.S. Gov't,Transcription Factors/*genetics},
pages = {424-30.},
volume = {9},
id = {91ee729d-ffc1-3b7b-bf6d-c403f36a37f2},
created = {2017-06-19T13:45:31.031Z},
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abstract = {Germline mutations of BRCA1 and BRCA2 predispose to hereditary breast-ovarian cancer syndrome. In Finland, 20 different BRCA1/2 mutations have been identified, and 13 of them are founder mutations that account for the vast majority of Finnish BRCA1/2 families. The purpose of our study was to determine the prevalence of BRCA1/2 mutations in unselected Finnish ovarian carcinoma patients and to evaluate the relationship between mutation carrier status and personal/family history of cancer. Two hundred and thirty-three patients were screened for all the 20 BRCA1/2 mutations known in the Finnish population. Additionally, a subgroup of patients with personal history of breast cancer and/or family history of breast and/or ovarian cancer was screened for novel BRCA1/2 mutations. Thirteen patients (5.6%) had mutations: eleven in BRCA1 and two in BRCA2. All the mutation-positive patients were carriers of the previously known Finnish BRCA1/2 mutations, and seven recurrent founder mutations accounted for 12 of the 13 mutations detected. A logistic regression analysis was used to determine the odds of mutation for ovarian carcinoma patients. The most significant predictor of a mutation was the presence of both breast and ovarian cancer in the same woman, but family history of breast cancer was also strongly related to mutation carrier status. Although BRCA1/2 mutation testing is not warranted in the general Finnish ovarian cancer patient population, patients who have also been diagnosed with breast cancer or have family history of breast or breast and ovarian cancer could benefit from referral to genetic counselling and mutation testing.},
bibtype = {article},
author = {Sarantaus, L and Vahteristo, P and Bloom, E and Tamminen, A and Unkila-Kallio, L and Butzow, R and Nevanlinna, H},
journal = {Eur J Hum Genet},
number = {6}
}Detecting association in a case-control study while correcting for population stratification. Reich, D., E. & Goldstein, D., B. Genet Epidemiol, 20(1):4-16., 2001.
Paper abstract bibtex
Paper abstract bibtex Case-control studies are subject to the problem of population stratification, which can occur in ethnically mixed populations and can lead to significant associations being detected at loci that have nothing to do with disease. Here, we describe a way to measure and correct for stratification by genotyping a moderate number of unlinked genetic markers in the same set of cases and controls in which a candidate association was found. The average of association statistics across the markers directly measures stratification. By dividing the candidate association statistic by this average, a P-value can be obtained that corrects for stratification.
@article{
title = {Detecting association in a case-control study while correcting for population stratification},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Case-Control Studies,*Selection Bias,Chromosome Mapping/*statistics & numerical data,Ethnic Groups/*statistics & numerical data,Gene Frequency,Human,Linkage Disequilibrium,Models, Genetic,Polymorphism, Single Nucleotide/*genetics,Support, Non-U.S. Gov't},
pages = {4-16.},
volume = {20},
id = {530b08ff-e5bc-39f0-8050-9dce4c0ec9ca},
created = {2017-06-19T13:45:09.287Z},
file_attached = {true},
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tags = {02/11/15},
read = {false},
starred = {false},
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hidden = {false},
source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article<m:linebreak/>Review<m:linebreak/>Review, Tutorial</m:note>},
abstract = {Case-control studies are subject to the problem of population stratification, which can occur in ethnically mixed populations and can lead to significant associations being detected at loci that have nothing to do with disease. Here, we describe a way to measure and correct for stratification by genotyping a moderate number of unlinked genetic markers in the same set of cases and controls in which a candidate association was found. The average of association statistics across the markers directly measures stratification. By dividing the candidate association statistic by this average, a P-value can be obtained that corrects for stratification.},
bibtype = {article},
author = {Reich, D E and Goldstein, D B},
journal = {Genet Epidemiol},
number = {1}
}Consanguinity decreases risk of breast cancer--cervical cancer unaffected. Denic, S. & Bener, A. Br J Cancer, 85(11):1675-9., 2001.
abstract bibtex
abstract bibtex
Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40-65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 - 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 - 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 - 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected.
@article{
title = {Consanguinity decreases risk of breast cancer--cervical cancer unaffected},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Consanguinity,Adult,Aged,Breast Neoplasms/*genetics,Cervix Neoplasms/*genetics,Cross-Sectional Studies,Family Health,Female,Health Surveys,Human,Male,Middle Age,Risk Factors,Socioeconomic Factors,Support, Non-U.S. Gov't,United Arab Emirates},
pages = {1675-9.},
volume = {85},
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abstract = {Marriages between third-degree and more distant relatives are common in many parts of the world. Offspring of consanguineous parents have increased morbidity and mortality related to recessive gene disorders. In a population with a high frequency of consanguinity, we examined the frequency of breast cancer (related in part to tumour genes) and cervical cancers (related to virus infection) among offspring of consanguineous and non-consanguineous parents. Study was done prospectively in the United Arab Emirates. Selected were married female citizens, ages 40-65, who attended 12 primary health care clinics for whatever reason. In a face-to-face interview, subjects were asked: (a) about consanguineous marriages in family; (b) if they have or have had breast or cervical cancer; (c) about family history of cancer, cancer screening and other parameters. Tumour diagnosis was confirmed by review of medical records. Of 1750 women invited into study, 1445 (79%) could be used in analysis. Among 579 (40%) women of consanguineous and 866 (60%) of non-consanguineous parents there were 24 and 54 with breast cancer, respectively (RR = 0.66, CI 0.42 - 1.06). In the 40 to 50 age group, breast cancer reported 13 of 446 women of consanguineous and 37 of 633 of non-consanguineous parents (RR = 0.50, Cl 0.27 - 0.93). Cervical cancer had 15 women in consanguineous and 32 in non-consanguineous group (RR = 0.70, Cl 0.38 - 1.28). Number of families with history of breast cancer in consanguineous and non-consanguineous group was 21 and 23, respectively (P = 0.29). The cancer screening rates and other variable values had fairly balanced distribution between the 2 groups. Having consanguineous parents decreases the risk of breast cancer especially in younger women, risk of cervical cancer being unaffected.},
bibtype = {article},
author = {Denic, S and Bener, A},
journal = {Br J Cancer},
number = {11}
}On a common circle: Natural scenes and Gestalt rules. Sigman, M, Cecchi, G., Gilbert, C., & Magnasco, M. Proc Natl Acad Sci U S A, 98(4):1935-40, 2001.
doi abstract bibtex
doi abstract bibtex
To understand how the human visual system analyzes images, it is essential to know the structure of the visual environment. In particular, natural images display consistent statistical properties that distinguish them from random luminance distributions. We have studied the geometric regularities of oriented elements (edges or line segments) present in an ensemble of visual scenes, asking how much information the presence of a segment in a particular location of the visual scene carries about the presence of a second segment at different relative positions and orientations. We observed strong long-range correlations in the distribution of oriented segments that extend over the whole visual field. We further show that a very simple geometric rule, cocircularity, predicts the arrangement of segments in natural scenes, and that different geometrical arrangements show relevant differences in their scaling properties. Our results show similarities to geometric features of previous physiological and psychophysical studies. We discuss the implications of these findings for theories of early vision.
@Article{Sigman2001,
author = {M Sigman and GA Cecchi and CD Gilbert and MO Magnasco},
journal = {Proc Natl Acad Sci U S A},
title = {On a common circle: {N}atural scenes and {G}estalt rules.},
year = {2001},
number = {4},
pages = {1935-40},
volume = {98},
abstract = {To understand how the human visual system analyzes images, it is essential
to know the structure of the visual environment. In particular, natural
images display consistent statistical properties that distinguish
them from random luminance distributions. We have studied the geometric
regularities of oriented elements (edges or line segments) present
in an ensemble of visual scenes, asking how much information the
presence of a segment in a particular location of the visual scene
carries about the presence of a second segment at different relative
positions and orientations. We observed strong long-range correlations
in the distribution of oriented segments that extend over the whole
visual field. We further show that a very simple geometric rule,
cocircularity, predicts the arrangement of segments in natural scenes,
and that different geometrical arrangements show relevant differences
in their scaling properties. Our results show similarities to geometric
features of previous physiological and psychophysical studies. We
discuss the implications of these findings for theories of early
vision.},
doi = {10.1073/pnas.031571498},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, Music, Probability, Arm, Cerebrovascular Disorders, Hemiplegia, Movement, Muscle, Skeletal, Myoclonus, Robotics, Magnetoencephalography, Phonetics, Software, Speech Production Measurement, Epilepsies, Partial, Laterality, Stereotaxic Techniques, Germany, Speech Acoustics, Verbal Behavior, Child Development, Instinct, Brain Stem, Coma, Diagnosis, Differential, Hearing Disorders, Hearing Loss, Central, Neuroma, Acoustic, Dendrites, Down-Regulation, Patch-Clamp Techniques, Wistar, Up-Regulation, Aged, Aphasia, Middle Aged, Cones (Retina), Primates, Retina, Retinal Ganglion Cells, Tympanic Membrane, Cell Communication, Extremities, Biological, Motor Activity, Rana catesbeiana, Spinal Cord, Central Nervous System, Motion, Motor Cortex, Intelligence, Macaca fascicularis, Adoption, Critical Period (Psychology), France, Korea, Magnetic Resonance Imaging, Multilingualism, Auditory Pathways, Cochlear Nerve, Loudness Perception, Neural Conduction, Sensory Thresholds, Sound, Language Disorders, Preschool, Generalization (Psychology), Vocabulary, Biophysics, Nerve Net, Potassium Channels, Sodium Channels, Cues, Differential Threshold, Arousal, Newborn, Sucking Behavior, Ferrets, Microelectrodes, Gestalt Theory, Mathematical Computing, Perceptual Closure, 11172054},
}Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Ikeda, N., Miyoshi, Y., Yoneda, K., Shiba, E., Sekihara, Y., Kinoshita, M., & Noguchi, S. Int J Cancer, 91(1):83-8., 2001.
abstract bibtex
abstract bibtex
The purpose of this investigation is to study the frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Mutation analysis of BRCA1 and BRCA2 by SSCP was conducted on the 113 breast cancer patients (probands) with at least 1 breast cancer (site-specific breast cancer families, n = 101) or 1 ovarian cancer (breast/ovarian cancer families, n = 12) patient in their first-degree relatives. Fifteen deleterious mutations (13.3%), including 8 nonsense and 7 frameshift mutations, were identified in BRCA1, and 21 deleterious mutations (18.6%), including 8 nonsense, 12 frameshift and 1 splice-site mutations, were identified in BRCA2. In site-specific breast cancer families, mutation frequency of BRCA1 or BRCA2 was high in families with 3 or more breast cancer patients (36%, 9/25), early onset (40 < or = years old) breast cancer patients (38%, 19/50) or bilateral breast cancer patients (40%, 6/15). In breast/ovarian cancer families, mutations of BRCA1 (58.3%, n = 7), but not BRCA2 (0%, n = 0), were observed. BRCA1 codon 63 (TTA to TAA) nonsense mutation and BRCA2 frameshift mutation (5802 del AATT) were observed in 4 and 7 independent families, respectively. Haplotype analysis has suggested that carriers of each of these mutations have common ancestors. These results demonstrate that family profiles are important determinants of risk for carrying a BRCA1 or BRCA2 mutation and that cumulative frequency of BRCA1 and BRCA2 mutations in Japanese breast cancer families (31.9%) is within the range observed in Caucasian breast cancer families. Presence of Japanese founder mutations has also been suggested.
@article{
title = {Frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Germ-Line Mutation,Adult,Aged,BRCA2 Protein,Breast Neoplasms, Male/*genetics,Breast Neoplasms/*genetics,Codon,Codon, Nonsense,DNA Mutational Analysis,Family Health,Female,Frameshift Mutation,Gene Deletion,Genes, BRCA1/*genetics,Haplotypes,Human,Japan,Male,Middle Age,Neoplasm Proteins/*genetics,Ovarian Neoplasms/genetics,Polymorphism (Genetics),Polymorphism, Single-Stranded Conformational,Support, Non-U.S. Gov't,Transcription Factors/*genetics},
pages = {83-8.},
volume = {91},
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source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {The purpose of this investigation is to study the frequency of BRCA1 and BRCA2 germline mutations in Japanese breast cancer families. Mutation analysis of BRCA1 and BRCA2 by SSCP was conducted on the 113 breast cancer patients (probands) with at least 1 breast cancer (site-specific breast cancer families, n = 101) or 1 ovarian cancer (breast/ovarian cancer families, n = 12) patient in their first-degree relatives. Fifteen deleterious mutations (13.3%), including 8 nonsense and 7 frameshift mutations, were identified in BRCA1, and 21 deleterious mutations (18.6%), including 8 nonsense, 12 frameshift and 1 splice-site mutations, were identified in BRCA2. In site-specific breast cancer families, mutation frequency of BRCA1 or BRCA2 was high in families with 3 or more breast cancer patients (36%, 9/25), early onset (40 < or = years old) breast cancer patients (38%, 19/50) or bilateral breast cancer patients (40%, 6/15). In breast/ovarian cancer families, mutations of BRCA1 (58.3%, n = 7), but not BRCA2 (0%, n = 0), were observed. BRCA1 codon 63 (TTA to TAA) nonsense mutation and BRCA2 frameshift mutation (5802 del AATT) were observed in 4 and 7 independent families, respectively. Haplotype analysis has suggested that carriers of each of these mutations have common ancestors. These results demonstrate that family profiles are important determinants of risk for carrying a BRCA1 or BRCA2 mutation and that cumulative frequency of BRCA1 and BRCA2 mutations in Japanese breast cancer families (31.9%) is within the range observed in Caucasian breast cancer families. Presence of Japanese founder mutations has also been suggested.},
bibtype = {article},
author = {Ikeda, N and Miyoshi, Y and Yoneda, K and Shiba, E and Sekihara, Y and Kinoshita, M and Noguchi, S},
journal = {Int J Cancer},
number = {1}
}The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data. Bahar, A., Y., Taylor, P., J., Andrews, L., Proos, A., Burnett, L., Tucker, K., Friedlander, M., & Buckley, M., F. Cancer, 92(2):440-5., 2001.
Paper abstract bibtex
Paper abstract bibtex BACKGROUND: Several studies have shown that Ashkenazi Jews in the United States and Israel have a high prevalence of the founder mutations BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT, and APC I1307K at frequencies of 1.0--1.1%, 0.2--0.3%, 0.6--1.4%, and 6.1--7.0%, respectively. The objective of this study was to compare the prevalence of these alleles in the Australian Jewish population with that of U.S. Jews. Australian Jews have a different history of migration, with less opportunity for changes in allele frequency due to conversion or intermarriage with non-Jewish Australians. The results obtained therefore can be used to assess whether U.S. data can be generalized to other Jewish populations. SUBJECTS AND METHODS. Subject samples were ascertained through a screening program for Tay-Sachs disease as part of a community-based screening program in New South Wales and Victoria. DNA extracted from 1200 deidentified blood samples was tested using amplification refractory mutation system polymerase chain reaction. RESULTS: The allele frequencies found were as follows: BRCA1 185delAG 1.25% (95% confidence interval [CI], 0.62--1.88%), BRCA1 5382insC 0.25% (95% CI, 0--0.53%), BRCA2 6174delT 1.08% (95% CI, 0.50--1.67%), and APC I1307K 8.67% (95% CI, 7.07--10.26%). The prevalence of breast carcinoma predisposition alleles therefore is greater than 2.5% in Australian Ashkenazim. CONCLUSIONS: There were no significant differences between the allele frequencies in Australian Ashkenazim and those identified in other studies with similar ascertainment strategies, despite the different migration patterns of Australian Jews. This suggests the broad applicability of the U.S. and Israeli data, not only to Australian Ashkenazim, but also to Ashkenazi communities throughout the world.
@article{
title = {The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data},
type = {article},
year = {2001},
identifiers = {[object Object]},
keywords = {*Founder Effect,Adult,Aged,Aged, 80 and over,Australia/ethnology,Breast Neoplasms/ethnology/etiology/*genetics,Carcinoma/ethnology/etiology/*genetics,Comparative Study,DNA Mutational Analysis,Emigration and Immigration,Female,Genes, APC/*genetics,Genes, BRCA1/*genetics,Human,Jews/*genetics,Mass Screening,Middle Age,Neoplasm Proteins/*genetics,Ovarian Neoplasms/genetics,Reference Values,Support, Non-U.S. Gov't,United States/ethnology},
pages = {440-5.},
volume = {92},
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source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {BACKGROUND: Several studies have shown that Ashkenazi Jews in the United States and Israel have a high prevalence of the founder mutations BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT, and APC I1307K at frequencies of 1.0--1.1%, 0.2--0.3%, 0.6--1.4%, and 6.1--7.0%, respectively. The objective of this study was to compare the prevalence of these alleles in the Australian Jewish population with that of U.S. Jews. Australian Jews have a different history of migration, with less opportunity for changes in allele frequency due to conversion or intermarriage with non-Jewish Australians. The results obtained therefore can be used to assess whether U.S. data can be generalized to other Jewish populations. SUBJECTS AND METHODS. Subject samples were ascertained through a screening program for Tay-Sachs disease as part of a community-based screening program in New South Wales and Victoria. DNA extracted from 1200 deidentified blood samples was tested using amplification refractory mutation system polymerase chain reaction. RESULTS: The allele frequencies found were as follows: BRCA1 185delAG 1.25% (95% confidence interval [CI], 0.62--1.88%), BRCA1 5382insC 0.25% (95% CI, 0--0.53%), BRCA2 6174delT 1.08% (95% CI, 0.50--1.67%), and APC I1307K 8.67% (95% CI, 7.07--10.26%). The prevalence of breast carcinoma predisposition alleles therefore is greater than 2.5% in Australian Ashkenazim. CONCLUSIONS: There were no significant differences between the allele frequencies in Australian Ashkenazim and those identified in other studies with similar ascertainment strategies, despite the different migration patterns of Australian Jews. This suggests the broad applicability of the U.S. and Israeli data, not only to Australian Ashkenazim, but also to Ashkenazi communities throughout the world.},
bibtype = {article},
author = {Bahar, A Y and Taylor, P J and Andrews, L and Proos, A and Burnett, L and Tucker, K and Friedlander, M and Buckley, M F},
journal = {Cancer},
number = {2}
}Broad and narrow heritabilities of quantitative traits in a founder population. Abney, M., McPeek, M., S., & Ober, C. Am J Hum Genet, 68(5):1302-7., 2001.
Paper abstract bibtex
Paper abstract bibtex Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and for choosing an appropriate model for linkage analysis. Using a recently developed method, we estimate the additive and dominance components of variance--or, equivalently, the narrow and broad sense heritabilities--of several traits in the Hutterites, a founder population with extensive genealogical records. As a result of inbreeding and because Hutterite individuals are typically related through multiple lines of descent, we expect that power to detect dominance variance will be increased relative to that in outbred studies. Furthermore, the communal lifestyle of the Hutterites allows us to evaluate the genetic influences in a relatively homogeneous environment. Four phenotypes had a significant dominance variance, resulting in a relatively high broad heritability. We estimated the narrow and broad heritabilities as being, respectively,.36 and.96 for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM). There was no significant additive component for systolic blood pressure (SBP), resulting in a narrow heritability of 0 and a broad heritability of.45. There were several traits for which we found no significant dominance component, resulting in equal broad and narrow heritability estimates. These traits and their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54. The large difference between broad and narrow heritabilities for LDL, serotonin, FFM, and SBP are indicative of strong dominance effects in these phenotypes. To our knowledge, this is the first study to report an estimate of heritability for serotonin and to detect a dominance variance for LDL, FFM, and SBP.
@article{
title = {Broad and narrow heritabilities of quantitative traits in a founder population},
type = {article},
year = {2001},
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pages = {1302-7.},
volume = {68},
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source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {Estimation of the components of variance for a quantitative trait allows one to evaluate both the degree to which genetics influences the trait and the trait's underlying genetic architecture. For particular traits, the estimates also may have implications for discriminating between potential models of selection and for choosing an appropriate model for linkage analysis. Using a recently developed method, we estimate the additive and dominance components of variance--or, equivalently, the narrow and broad sense heritabilities--of several traits in the Hutterites, a founder population with extensive genealogical records. As a result of inbreeding and because Hutterite individuals are typically related through multiple lines of descent, we expect that power to detect dominance variance will be increased relative to that in outbred studies. Furthermore, the communal lifestyle of the Hutterites allows us to evaluate the genetic influences in a relatively homogeneous environment. Four phenotypes had a significant dominance variance, resulting in a relatively high broad heritability. We estimated the narrow and broad heritabilities as being, respectively,.36 and.96 for LDL,.51 and 1.0 for serotonin levels, and.45 and.76 for fat free mass (FFM). There was no significant additive component for systolic blood pressure (SBP), resulting in a narrow heritability of 0 and a broad heritability of.45. There were several traits for which we found no significant dominance component, resulting in equal broad and narrow heritability estimates. These traits and their heritabilities are as follows: HDL,.63; triglycerides,.37; diastolic blood pressure,.21; immunoglobulin E,.63; lipoprotein(a),.77; and body-mass index,.54. The large difference between broad and narrow heritabilities for LDL, serotonin, FFM, and SBP are indicative of strong dominance effects in these phenotypes. To our knowledge, this is the first study to report an estimate of heritability for serotonin and to detect a dominance variance for LDL, FFM, and SBP.},
bibtype = {article},
author = {Abney, M and McPeek, M S and Ober, C},
journal = {Am J Hum Genet},
number = {5}
}2000 (16)
Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland. van Der Looij, M., Wysocka, B., Brozek, I., Jassem, J., Limon, J., & Olah, E. Hum Mutat, 15(5):480-1., 2000.
abstract bibtex
abstract bibtex
Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.
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pages = {480-1.},
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abstract = {Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.},
bibtype = {article},
author = {van Der Looij, M and Wysocka, B and Brozek, I and Jassem, J and Limon, J and Olah, E},
journal = {Hum Mutat},
number = {5}
}Why are the majority of hereditary cases of early-onset breast cancer sporadic? A simulation study. Cui, J. & Hopper, J., L. Cancer Epidemiol Biomarkers Prev, 9(8):805-12., 2000.
Paper abstract bibtex
Paper abstract bibtex Population-based studies, including those of Ashkenazi Jews, have observed that at least 50% of women with early-onset breast cancer who carry a germ line mutation in BRCA1 or BRCA2 do not report a family history of the disease. That is, the majority of "hereditary" cases are "sporadic." Furthermore, the great majority of "familial breast cancers" are not hereditary. We conducted a simulation study to evaluate the probability that a woman with early-onset breast cancer is a mutation carrier, given the number of affected relatives, for a range of plausible values of allele frequency (0.001-0.01), and increased risk in mutation carriers (5-20, equivalent to cumulative risks to age 70 of 25-70%, respectively, for Australian women). Families consisted of a case proband and her mother, sisters, and maternal and paternal grandmothers, and aunts. The numbers of sisters and aunts were generated according to Poisson distributions, and ages were assigned according to a Weibull distribution. The simulated distributions of family history and of the prevalence of mutation carriers among case probands were in general similar to those observed in population-based studies, although there was a suggestion of heterogeneity of breast cancer risk in mutation carriers. As is being observed empirically in population-based samples, a family history of breast cancer was not a strong predictor of mutation status; each affected female relative increased the risk of being a mutation carrier by only 2- to 3-fold. The probability of being a mutation carrier was generally low, except in families with extreme histories of breast cancer.
@article{
title = {Why are the majority of hereditary cases of early-onset breast cancer sporadic? A simulation study},
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abstract = {Population-based studies, including those of Ashkenazi Jews, have observed that at least 50% of women with early-onset breast cancer who carry a germ line mutation in BRCA1 or BRCA2 do not report a family history of the disease. That is, the majority of "hereditary" cases are "sporadic." Furthermore, the great majority of "familial breast cancers" are not hereditary. We conducted a simulation study to evaluate the probability that a woman with early-onset breast cancer is a mutation carrier, given the number of affected relatives, for a range of plausible values of allele frequency (0.001-0.01), and increased risk in mutation carriers (5-20, equivalent to cumulative risks to age 70 of 25-70%, respectively, for Australian women). Families consisted of a case proband and her mother, sisters, and maternal and paternal grandmothers, and aunts. The numbers of sisters and aunts were generated according to Poisson distributions, and ages were assigned according to a Weibull distribution. The simulated distributions of family history and of the prevalence of mutation carriers among case probands were in general similar to those observed in population-based studies, although there was a suggestion of heterogeneity of breast cancer risk in mutation carriers. As is being observed empirically in population-based samples, a family history of breast cancer was not a strong predictor of mutation status; each affected female relative increased the risk of being a mutation carrier by only 2- to 3-fold. The probability of being a mutation carrier was generally low, except in families with extreme histories of breast cancer.},
bibtype = {article},
author = {Cui, J and Hopper, J L},
journal = {Cancer Epidemiol Biomarkers Prev},
number = {8}
}The genetically isolated populations of Finland and sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes. Eaves, I., A., Merriman, T., R., Barber, R., A., Nutland, S., Tuomilehto-Wolf, E., Tuomilehto, J., Cucca, F., & Todd, J., A. Nat Genet, 25(3):320-3., 2000.
Paper Website abstract bibtex
Paper Website abstract bibtex The choice of which population to study in the mapping of common disease genes may be critical. Isolated founder populations, such as that found in Finland, have already proved extremely useful for mapping the genes for specific rare monogenic disorders and are being used in attempts to map the genes underlying common, complex diseases. But simulation results suggest that, under the common disease-common variant hypothesis, most isolated populations will prove no more useful for linkage disequilibrium (LD) mapping of common disease genes than large outbred populations. There is very little empirical data to either support or refute this conclusion at present. Therefore, we evaluated LD between 21 common microsatellite polymorphisms on chromosome 18q21 in 2 genetic isolates (Finland and Sardinia) and compared the results with those observed in two mixed populations (United Kingdom and United States of America). Mean levels of LD were similar across all four populations. Our results provide empirical support for the expectation that genetic isolates like Finland and Sardinia will not prove significantly more valuable than general populations for LD mapping of common variants underlying complex disease.
@article{
title = {The genetically isolated populations of Finland and sardinia may not be a panacea for linkage disequilibrium mapping of common disease genes},
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pages = {320-3.},
volume = {25},
websites = {http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v25/n3/full/ng0700_320.html,http://www.nature.com/cgi-taf/DynaPage.taf?file=/ng/journal/v25/n3/abs/ng0700_320.html},
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abstract = {The choice of which population to study in the mapping of common disease genes may be critical. Isolated founder populations, such as that found in Finland, have already proved extremely useful for mapping the genes for specific rare monogenic disorders and are being used in attempts to map the genes underlying common, complex diseases. But simulation results suggest that, under the common disease-common variant hypothesis, most isolated populations will prove no more useful for linkage disequilibrium (LD) mapping of common disease genes than large outbred populations. There is very little empirical data to either support or refute this conclusion at present. Therefore, we evaluated LD between 21 common microsatellite polymorphisms on chromosome 18q21 in 2 genetic isolates (Finland and Sardinia) and compared the results with those observed in two mixed populations (United Kingdom and United States of America). Mean levels of LD were similar across all four populations. Our results provide empirical support for the expectation that genetic isolates like Finland and Sardinia will not prove significantly more valuable than general populations for LD mapping of common variants underlying complex disease.},
bibtype = {article},
author = {Eaves, I A and Merriman, T R and Barber, R A and Nutland, S and Tuomilehto-Wolf, E and Tuomilehto, J and Cucca, F and Todd, J A},
journal = {Nat Genet},
number = {3}
}Familial cancer risks to offspring from mothers with 2 primary breast cancers: leads to cancer syndromes. Hemminki, K., Vaittinen, P., & Easton, D. Int J Cancer, 88(1):87-91., 2000.
abstract bibtex
abstract bibtex
The nationwide Swedish Family-Cancer Database was used to analyse the risk of cancer among the offspring of bilateral breast cancer patients. We studied 4,734 such mothers who had 9,391 offspring, of whom 328 presented with a primary cancer in the years 1958-1996. Standardised incidence ratios (SIRs) were increased for breast [SIR 3.05, 95% confidence interval (CI) 2.57-3.59], ovarian (SIR 1.84, 95% CI 1.03-3.05) and anogenital (SIR 1.75, 95% CI 1.11-2.63) cancers and childhood sarcomas (SIR 9.39, 95% CI 1.93-29.13). Additionally, squamous-cell skin cancer was increased among sons and all childhood cancers among daughters. When analysed by histological type, adenocarcinomas of the breast and ovary, all squamous-cell carcinomas and tumours at glandular epithelium (seminomas and intestinal carcinoids) were increased. Mothers with bilateral breast cancer had an excess of 2 or more children with cancer. The increased risk of ovarian cancer is consistent with germline mutations in the BRCA1 and BRCA2 genes, while the risk of soft tissue and bone sarcomas may reflect the association of these tumours with Li-Fraumeni syndrome. The increases in squamous-cell carcinomas at many sites may reflect a new susceptibility syndrome.
@article{
title = {Familial cancer risks to offspring from mothers with 2 primary breast cancers: leads to cancer syndromes},
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year = {2000},
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pages = {87-91.},
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abstract = {The nationwide Swedish Family-Cancer Database was used to analyse the risk of cancer among the offspring of bilateral breast cancer patients. We studied 4,734 such mothers who had 9,391 offspring, of whom 328 presented with a primary cancer in the years 1958-1996. Standardised incidence ratios (SIRs) were increased for breast [SIR 3.05, 95% confidence interval (CI) 2.57-3.59], ovarian (SIR 1.84, 95% CI 1.03-3.05) and anogenital (SIR 1.75, 95% CI 1.11-2.63) cancers and childhood sarcomas (SIR 9.39, 95% CI 1.93-29.13). Additionally, squamous-cell skin cancer was increased among sons and all childhood cancers among daughters. When analysed by histological type, adenocarcinomas of the breast and ovary, all squamous-cell carcinomas and tumours at glandular epithelium (seminomas and intestinal carcinoids) were increased. Mothers with bilateral breast cancer had an excess of 2 or more children with cancer. The increased risk of ovarian cancer is consistent with germline mutations in the BRCA1 and BRCA2 genes, while the risk of soft tissue and bone sarcomas may reflect the association of these tumours with Li-Fraumeni syndrome. The increases in squamous-cell carcinomas at many sites may reflect a new susceptibility syndrome.},
bibtype = {article},
author = {Hemminki, K and Vaittinen, P and Easton, D},
journal = {Int J Cancer},
number = {1}
}Germ line BRCA1 and BRCA2 gene mutations in Turkish breast cancer patients. Ozdag, H., Tez, M., Sayek, I., Muslumanoglu, M., Tarcan, O., Icli, F., Ozturk, M., & Ozcelik, T. Eur J Cancer, 36(16):2076-82., 2000.
abstract bibtex
abstract bibtex
Germ line BRCA1 and/or BRCA2 mutations were screened in 50 Turkish breast and/or ovarian cancer patients composed of hereditary, familial, early onset and male cancer groups. Genomic DNA samples were tested by heteroduplex analysis and DNA sequencing. Two truncating BRCA2 mutations, one novel (6880 insG) and one previously reported (3034 delAAAC), were found in two out of six (33%) hereditary breast and/or ovarian cancer patients. A novel truncating (1200 insA) and a missense (2080A-->G) BRCA1 mutation was found in two of 27 (7%) individuals in the early onset group. A total of four (8%) disease-causing mutations in 50 breast cancer patients were identified in BRCA1 and BRCA2 genes. In addition, five BRCA1 sequence variants have been identified in 23 patients. These results indicate that BRCA1 and BRCA2 genes are involved in some, but not all, forms of hereditary predisposition to breast cancer in the Turkish population.
@article{
title = {Germ line BRCA1 and BRCA2 gene mutations in Turkish breast cancer patients},
type = {article},
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abstract = {Germ line BRCA1 and/or BRCA2 mutations were screened in 50 Turkish breast and/or ovarian cancer patients composed of hereditary, familial, early onset and male cancer groups. Genomic DNA samples were tested by heteroduplex analysis and DNA sequencing. Two truncating BRCA2 mutations, one novel (6880 insG) and one previously reported (3034 delAAAC), were found in two out of six (33%) hereditary breast and/or ovarian cancer patients. A novel truncating (1200 insA) and a missense (2080A-->G) BRCA1 mutation was found in two of 27 (7%) individuals in the early onset group. A total of four (8%) disease-causing mutations in 50 breast cancer patients were identified in BRCA1 and BRCA2 genes. In addition, five BRCA1 sequence variants have been identified in 23 patients. These results indicate that BRCA1 and BRCA2 genes are involved in some, but not all, forms of hereditary predisposition to breast cancer in the Turkish population.},
bibtype = {article},
author = {Ozdag, H and Tez, M and Sayek, I and Muslumanoglu, M and Tarcan, O and Icli, F and Ozturk, M and Ozcelik, T},
journal = {Eur J Cancer},
number = {16}
}Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion. Labuda, M., Labuda, D., Miranda, C., Poirier, J., Soong, B., W., Barucha, N., E., & Pandolfo, M. Neurology, 54(12):2322-4., 2000.
Paper abstract bibtex
Paper abstract bibtex The GAA triplet repeat expansion that causes Friedreich ataxia is found only in individuals of European, North African, Middle Eastern, or Indian origin (Indo-European and Afro-Asiatic speakers). Analysis of normal alleles of the GAA repeat and of closely linked markers suggests that expansions arose through a unique two-step process. A major implication of these findings is that Friedreich ataxia may not exist among sub-Saharan Africans, Amerindians, and people from China, Japan, and Southeast Asia.
@article{
title = {Unique origin and specific ethnic distribution of the Friedreich ataxia GAA expansion},
type = {article},
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abstract = {The GAA triplet repeat expansion that causes Friedreich ataxia is found only in individuals of European, North African, Middle Eastern, or Indian origin (Indo-European and Afro-Asiatic speakers). Analysis of normal alleles of the GAA repeat and of closely linked markers suggests that expansions arose through a unique two-step process. A major implication of these findings is that Friedreich ataxia may not exist among sub-Saharan Africans, Amerindians, and people from China, Japan, and Southeast Asia.},
bibtype = {article},
author = {Labuda, M and Labuda, D and Miranda, C and Poirier, J and Soong, B W and Barucha, N E and Pandolfo, M},
journal = {Neurology},
number = {12}
}Consistent long-range linkage disequilibrium generated by admixture in a Bantu-Semitic hybrid population. Wilson, J., F. & Goldstein, D., B. Am J Hum Genet, 67(4):926-35., 2000.
Paper abstract bibtex
Paper abstract bibtex Both the optimal marker density for genome scans in case-control association studies and the appropriate study design for the testing of candidate genes depend on the genomic pattern of linkage disequilibrium (LD). In this study, we provide the first conclusive demonstration that the diverse demographic histories of human populations have produced dramatic differences in genomewide patterns of LD. Using a panel of 66 markers spanning the X chromosome, we show that, in the Lemba, a Bantu-Semitic hybrid population, markers 2 cM. Moreover, analysis of Bantu and Ashkenazi populations as putative parental populations of the Lemba shows a significant relationship between allele-frequency differentials and the LD observed in the Lemba, which demonstrates that much of the excess LD is due to admixture. Our results suggest that demographic history has such a profound effect on LD that it will not be possible to predict patterns a priori but that it will be necessary to empirically evaluate the patterns in all populations of interest.
@article{
title = {Consistent long-range linkage disequilibrium generated by admixture in a Bantu-Semitic hybrid population},
type = {article},
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pages = {926-35.},
volume = {67},
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abstract = {Both the optimal marker density for genome scans in case-control association studies and the appropriate study design for the testing of candidate genes depend on the genomic pattern of linkage disequilibrium (LD). In this study, we provide the first conclusive demonstration that the diverse demographic histories of human populations have produced dramatic differences in genomewide patterns of LD. Using a panel of 66 markers spanning the X chromosome, we show that, in the Lemba, a Bantu-Semitic hybrid population, markers </= approximately 21 cM apart have a significantly greater tendency to show LD than do unlinked markers. In three populations with less evidence of admixture, however, excess LD disappears >2 cM. Moreover, analysis of Bantu and Ashkenazi populations as putative parental populations of the Lemba shows a significant relationship between allele-frequency differentials and the LD observed in the Lemba, which demonstrates that much of the excess LD is due to admixture. Our results suggest that demographic history has such a profound effect on LD that it will not be possible to predict patterns a priori but that it will be necessary to empirically evaluate the patterns in all populations of interest.},
bibtype = {article},
author = {Wilson, J F and Goldstein, D B},
journal = {Am J Hum Genet},
number = {4}
}BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer. Moslehi, R., Chu, W., Karlan, B., Fishman, D., Risch, H., Fields, A., Smotkin, D., Ben-David, Y., Rosenblatt, J., Russo, D., Schwartz, P., Tung, N., Warner, E., Rosen, B., Friedman, J., Brunet, J., S., & Narod, S., A. Am J Hum Genet, 66(4):1259-72., 2000.
abstract bibtex
abstract bibtex
Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in approximately 2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 41.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P=.002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P=.0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.
@article{
title = {BRCA1 and BRCA2 mutation analysis of 208 Ashkenazi Jewish women with ovarian cancer},
type = {article},
year = {2000},
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keywords = {*Founder Effect,Adult,Aged,Aged, 80 and over,Breast Neoplasms/epidemiology/genetics,DNA Mutational Analysis,Female,Gene Frequency/genetics,Genes, BRCA1/*genetics,Genetic Predisposition to Disease/genetics,Human,Incidence,Israel/epidemiology,Jews/*genetics,Male,Middle Age,Mutation/*genetics,Neoplasm Proteins/*genetics,Neoplasm Staging,North America/epidemiology,Ovarian Neoplasms/epidemiology/*genetics/mortality,Pedigree,Support, Non-U.S. Gov't,Support, U.S. Gov't, Non-P.H.S.,Support, U.S. Gov't, P.H.S.,Transcription Factors/*genetics},
pages = {1259-72.},
volume = {66},
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notes = {<m:note>eng<m:linebreak/>Journal Article<m:linebreak/>Multicenter Study</m:note>},
abstract = {Ovarian cancer is a component of the autosomal-dominant hereditary breast-ovarian cancer syndrome and may be due to a mutation in either the BRCA1 or BRCA2 genes. Two mutations in BRCA1 (185delAG and 5382insC) and one mutation in BRCA2 (6174delT) are common in the Ashkenazi Jewish population. One of these three mutations is present in approximately 2% of the Jewish population. Each mutation is associated with an increased risk of ovarian cancer, and it is expected that a significant proportion of Jewish women with ovarian cancer will carry one of these mutations. To estimate the proportion of ovarian cancers attributable to founding mutations in BRCA1 and BRCA2 in the Jewish population and the familial cancer risks associated with each, we interviewed 213 Jewish women with ovarian cancer at 11 medical centers in North America and Israel and offered these women genetic testing for the three founder mutations. To establish the presence of nonfounder mutations in this population, we also completed the protein-truncation test on exon 11 of BRCA1 and exons 10 and 11 of BRCA2. We obtained a detailed family history on all women we studied who had cancer and on a control population of 386 Ashkenazi Jewish women without ovarian or breast cancer. A founder mutation was present in 41.3% of the women we studied. The cumulative incidence of ovarian cancer to age 75 years was found to be 6.3% for female first-degree relatives of the patients with ovarian cancer, compared with 2.0% for the female relatives of healthy controls (relative risk 3.2; 95% CI 1.5-6.8; P=.002). The relative risk to age 75 years for breast cancer among the female first-degree relatives was 2.0 (95% CI 1.4-3.0; P=.0001). Only one nonfounder mutation was identified (in this instance, in a woman of mixed ancestry), and the three founding mutations accounted for most of the observed excess risk of ovarian and breast cancer in relatives.},
bibtype = {article},
author = {Moslehi, R and Chu, W and Karlan, B and Fishman, D and Risch, H and Fields, A and Smotkin, D and Ben-David, Y and Rosenblatt, J and Russo, D and Schwartz, P and Tung, N and Warner, E and Rosen, B and Friedman, J and Brunet, J S and Narod, S A},
journal = {Am J Hum Genet},
number = {4}
}Gene Mapping in the 20th and 21st Centuries : Statistical Methods , Data Analysis, and Experimental Design. Terwilliger, J., D. & Goring, H., H., H. Human Biology, 72(1):63-132, 2000.
Paper abstract bibtex
Paper abstract bibtex In the 20th century geneticists began to unravel some of the simpler aspects of the etiology of inherited diseases in humans. The theory of linkage analysis was developed and applied long before the advent of molecular biology, but only the technological advances of the second half of the 20th century made large-scale gene mapping with a dense genome-spanning set of markers a reality. More recently, the primary topic of interest has shifted from simple Mendelian diseases, for which genotypes of some gene are the cause of disease, to more complex diseases, for which genotypes of some set of genes together with environmental factors merely alter the probability that an individual gets the disease, although individual factors are typically insufficient to cause the disease outright. To this end, a great deal of dogma has evolved about the best way to skin this cat, although to date success has been minimal with any approach. We postulate that the main reason for this is a lack of attention to experimental design. Once the data have been ascertained, the most powerful statistical methods will not be able to salvage an inappropriately designed study (Andersen 1990). Each phenotype and/or population mandates its own individually tailored study design to maximize the chances of successful gene mapping. We suggest that careful consideration of the available data from real genotype-phenotype correlation studies (as opposed to oversimplified theoretically tractable models), and the practical feasibility of different ascertainment schemes dictate how one should proceed. In this review we review the theory and practice of gene mapping at the close of the 20th century, showing that most methods of linkage and linkage disequilibrium analysis are similar in a fundamental sense, with the differences being related more to study design and ascertainment than to technical details of the underlying statistical analysis. To this end, we propose a new focus in the field of statistical genetics that more explicitly highlights the primacy of study design as the means to increase power for gene mapping.
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title = {Gene Mapping in the 20th and 21st Centuries : Statistical Methods , Data Analysis, and Experimental Design},
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abstract = {In the 20th century geneticists began to unravel some of the simpler aspects of the etiology of inherited diseases in humans. The theory of linkage analysis was developed and applied long before the advent of molecular biology, but only the technological advances of the second half of the 20th century made large-scale gene mapping with a dense genome-spanning set of markers a reality. More recently, the primary topic of interest has shifted from simple Mendelian diseases, for which genotypes of some gene are the cause of disease, to more complex diseases, for which genotypes of some set of genes together with environmental factors merely alter the probability that an individual gets the disease, although individual factors are typically insufficient to cause the disease outright. To this end, a great deal of dogma has evolved about the best way to skin this cat, although to date success has been minimal with any approach. We postulate that the main reason for this is a lack of attention to experimental design. Once the data have been ascertained, the most powerful statistical methods will not be able to salvage an inappropriately designed study (Andersen 1990). Each phenotype and/or population mandates its own individually tailored study design to maximize the chances of successful gene mapping. We suggest that careful consideration of the available data from real genotype-phenotype correlation studies (as opposed to oversimplified theoretically tractable models), and the practical feasibility of different ascertainment schemes dictate how one should proceed. In this review we review the theory and practice of gene mapping at the close of the 20th century, showing that most methods of linkage and linkage disequilibrium analysis are similar in a fundamental sense, with the differences being related more to study design and ascertainment than to technical details of the underlying statistical analysis. To this end, we propose a new focus in the field of statistical genetics that more explicitly highlights the primacy of study design as the means to increase power for gene mapping.},
bibtype = {article},
author = {Terwilliger, Joseph D and Goring, Harald H H},
journal = {Human Biology},
number = {1}
}Data mining applied to linkage disequilibrium mapping. Toivonen, H., T., Onkamo, P., Vasko, K., Ollikainen, V., Sevon, P., Mannila, H., Herr, M., & Kere, J. Am J Hum Genet, 67(1):133-45., 2000.
abstract bibtex
abstract bibtex
We introduce a new method for linkage disequilibrium mapping: haplotype pattern mining (HPM). The method, inspired by data mining methods, is based on discovery of recurrent patterns. We define a class of useful haplotype patterns in genetic case-control data and use the algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association with the phenotype, and all haplotypes exceeding a given threshold level are used for prediction of disease susceptibility-gene location. The method is model-free, in the sense that it does not require (and is unable to utilize) any assumptions about the inheritance model of the disease. The statistical model is nonparametric. The haplotypes are allowed to contain gaps, which improves the method's robustness to mutations and to missing and erroneous data. Experimental studies with simulated microsatellite and SNP data show that the method has good localization power in data sets with large degrees of phenocopies and with lots of missing and erroneous data. The power of HPM is roughly identical for marker maps at a density of 3 single-nucleotide polymorphisms/cM or 1 microsatellite/cM. The capacity to handle high proportions of phenocopies makes the method promising for complex disease mapping. An example of correct disease susceptibility-gene localization with HPM is given with real marker data from families from the United Kingdom affected by type 1 diabetes. The method is extendable to include environmental covariates or phenotype measurements or to find several genes simultaneously.
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title = {Data mining applied to linkage disequilibrium mapping},
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pages = {133-45.},
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abstract = {We introduce a new method for linkage disequilibrium mapping: haplotype pattern mining (HPM). The method, inspired by data mining methods, is based on discovery of recurrent patterns. We define a class of useful haplotype patterns in genetic case-control data and use the algorithm for finding disease-associated haplotypes. The haplotypes are ordered by their strength of association with the phenotype, and all haplotypes exceeding a given threshold level are used for prediction of disease susceptibility-gene location. The method is model-free, in the sense that it does not require (and is unable to utilize) any assumptions about the inheritance model of the disease. The statistical model is nonparametric. The haplotypes are allowed to contain gaps, which improves the method's robustness to mutations and to missing and erroneous data. Experimental studies with simulated microsatellite and SNP data show that the method has good localization power in data sets with large degrees of phenocopies and with lots of missing and erroneous data. The power of HPM is roughly identical for marker maps at a density of 3 single-nucleotide polymorphisms/cM or 1 microsatellite/cM. The capacity to handle high proportions of phenocopies makes the method promising for complex disease mapping. An example of correct disease susceptibility-gene localization with HPM is given with real marker data from families from the United Kingdom affected by type 1 diabetes. The method is extendable to include environmental covariates or phenotype measurements or to find several genes simultaneously.},
bibtype = {article},
author = {Toivonen, H T and Onkamo, P and Vasko, K and Ollikainen, V and Sevon, P and Mannila, H and Herr, M and Kere, J},
journal = {Am J Hum Genet},
number = {1}
}Association mapping in structured populations. Pritchard, J., K., Stephens, M., Rosenberg, N., A., & Donnelly, P. Am J Hum Genet, 67(1):170-81., 2000.
Paper abstract bibtex
Paper abstract bibtex The use, in association studies, of the forthcoming dense genomewide collection of single-nucleotide polymorphisms (SNPs) has been heralded as a potential breakthrough in the study of the genetic basis of common complex disorders. A serious problem with association mapping is that population structure can lead to spurious associations between a candidate marker and a phenotype. One common solution has been to abandon case-control studies in favor of family-based tests of association, such as the transmission/disequilibrium test (TDT), but this comes at a considerable cost in the need to collect DNA from close relatives of affected individuals. In this article we describe a novel, statistically valid, method for case-control association studies in structured populations. Our method uses a set of unlinked genetic markers to infer details of population structure, and to estimate the ancestry of sampled individuals, before using this information to test for associations within subpopulations. It provides power comparable with the TDT in many settings and may substantially outperform it if there are conflicting associations in different subpopulations.
@article{
title = {Association mapping in structured populations},
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year = {2000},
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pages = {170-81.},
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notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {The use, in association studies, of the forthcoming dense genomewide collection of single-nucleotide polymorphisms (SNPs) has been heralded as a potential breakthrough in the study of the genetic basis of common complex disorders. A serious problem with association mapping is that population structure can lead to spurious associations between a candidate marker and a phenotype. One common solution has been to abandon case-control studies in favor of family-based tests of association, such as the transmission/disequilibrium test (TDT), but this comes at a considerable cost in the need to collect DNA from close relatives of affected individuals. In this article we describe a novel, statistically valid, method for case-control association studies in structured populations. Our method uses a set of unlinked genetic markers to infer details of population structure, and to estimate the ancestry of sampled individuals, before using this information to test for associations within subpopulations. It provides power comparable with the TDT in many settings and may substantially outperform it if there are conflicting associations in different subpopulations.},
bibtype = {article},
author = {Pritchard, J K and Stephens, M and Rosenberg, N A and Donnelly, P},
journal = {Am J Hum Genet},
number = {1}
}Surnames and the Y chromosome. Sykes, B. & Irven, C. Am J Hum Genet, 66(4):1417-9., 2000.
Paper abstract bibtex
Paper abstract bibtex A randomly ascertained sample of males with the surname "Sykes" was typed with four Y-chromosome microsatellites. Almost half the sample shared the same Y-chromosome haplotype, which has not been observed in control samples either from the same geographic region or from the United Kingdom as a whole. This points to a single surname founder for extant Sykes males, even though written sources had predicted multiple origins. The distribution of other Sykes Y-chromosome haplotypes were not significantly different from those in controls and may be accounted for by the historical accumulation of nonpaternity during the past 700 years, in which case the average rate estimate is 1.3%/generation. If this pattern is reproduced with other surnames, it may have important forensic and genealogical applications.
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title = {Surnames and the Y chromosome},
type = {article},
year = {2000},
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pages = {1417-9.},
volume = {66},
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abstract = {A randomly ascertained sample of males with the surname "Sykes" was typed with four Y-chromosome microsatellites. Almost half the sample shared the same Y-chromosome haplotype, which has not been observed in control samples either from the same geographic region or from the United Kingdom as a whole. This points to a single surname founder for extant Sykes males, even though written sources had predicted multiple origins. The distribution of other Sykes Y-chromosome haplotypes were not significantly different from those in controls and may be accounted for by the historical accumulation of nonpaternity during the past 700 years, in which case the average rate estimate is 1.3%/generation. If this pattern is reproduced with other surnames, it may have important forensic and genealogical applications.},
bibtype = {article},
author = {Sykes, B and Irven, C},
journal = {Am J Hum Genet},
number = {4}
}Estimation of variance components of quantitative traits in inbred populations. Abney, M., McPeek, M., S., & Ober, C. Am J Hum Genet, 66(2):629-50., 2000.
Paper Website abstract bibtex
Paper Website abstract bibtex Use of variance-component estimation for mapping of quantitative-trait loci in humans is a subject of great current interest. When only trait values, not genotypic information, are considered, variance-component estimation can also be used to estimate heritability of a quantitative trait. Inbred pedigrees present special challenges for variance-component estimation. First, there are more variance components to be estimated in the inbred case, even for a relatively simple model including additive, dominance, and environmental effects. Second, more identity coefficients need to be calculated from an inbred pedigree in order to perform the estimation, and these are computationally more difficult to obtain in the inbred than in the outbred case. As a result, inbreeding effects have generally been ignored in practice. We describe here the calculation of identity coefficients and estimation of variance components of quantitative traits in large inbred pedigrees, using the example of HDL in the Hutterites. We use a multivariate normal model for the genetic effects, extending the central-limit theorem of Lange to allow for both inbreeding and dominance under the assumptions of our variance-component model. We use simulated examples to give an indication of under what conditions one has the power to detect the additional variance components and to examine their impact on variance-component estimation. We discuss the implications for mapping and heritability estimation by use of variance components in inbred populations.
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title = {Estimation of variance components of quantitative traits in inbred populations},
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year = {2000},
identifiers = {[object Object]},
keywords = {*Computer Simulation,*Consanguinity,*Models, Genetic,*Quantitative Trait,Algorithms,Alleles,Child,Christianity,Environment,Female,Genes, Dominant/genetics,Human,Likelihood Functions,Lipoproteins, HDL/genetics,Male,Matched-Pair Analysis,Multivariate Analysis,Pedigree,Sample Size,South Dakota,Support, Non-U.S. Gov't,Support, U.S. Gov't, P.H.S.},
pages = {629-50.},
volume = {66},
websites = {http://www.journals.uchicago.edu/cgi-bin/resolve?AJHG991109ABS},
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abstract = {Use of variance-component estimation for mapping of quantitative-trait loci in humans is a subject of great current interest. When only trait values, not genotypic information, are considered, variance-component estimation can also be used to estimate heritability of a quantitative trait. Inbred pedigrees present special challenges for variance-component estimation. First, there are more variance components to be estimated in the inbred case, even for a relatively simple model including additive, dominance, and environmental effects. Second, more identity coefficients need to be calculated from an inbred pedigree in order to perform the estimation, and these are computationally more difficult to obtain in the inbred than in the outbred case. As a result, inbreeding effects have generally been ignored in practice. We describe here the calculation of identity coefficients and estimation of variance components of quantitative traits in large inbred pedigrees, using the example of HDL in the Hutterites. We use a multivariate normal model for the genetic effects, extending the central-limit theorem of Lange to allow for both inbreeding and dominance under the assumptions of our variance-component model. We use simulated examples to give an indication of under what conditions one has the power to detect the additional variance components and to examine their impact on variance-component estimation. We discuss the implications for mapping and heritability estimation by use of variance components in inbred populations.},
bibtype = {article},
author = {Abney, M and McPeek, M S and Ober, C},
journal = {Am J Hum Genet},
number = {2}
}Development and testing of a clinical tool measuring self-management of heart failure. Riegel, B., Carlson, B., & Glaser, D. Heart Lung, 29(1):4–15, 2000.
abstract bibtex
abstract bibtex
BACKGROUND: Self-management is a primary goal of treatment for heart failure. Yet no measure of self-management in this patient group currently exists. OBJECTIVES: To develop a clinically useful measure of the abilities of patients with heart failure to manage their disease. Self-management in this context was defined as a cognitive decision-making process undertaken in response to signs and symptoms of heart failure. A panel of experts agreed that the process involved 4 distinct stages: recognizing a change, evaluating the change, implementing a treatment strategy, and evaluating the treatment. The tool was developed to reflect this process. METHODS: Face validity of the process model was assessed in a sample of 25 patients with heart failure and used to develop a 65-item tool with 6 subscales. The subscales measure the 4 stages as well as the patients' ease in evaluating the signs and symptoms and their self-efficacy. The tool was pilot tested with 2 samples of patients with heart failure (N = 17; N = 129). Psychometrics of the final tool were then tested in a sample of 127 patients with heart failure. RESULTS: Face and content validity of the tool were demonstrated adequately through this study. Internal consistency scores of the 6 subscales of the Self-Management of Heart Failure instrument ranged from 0.79 (ease of evaluating treatment) to 0.92 (evaluating the change). Reliability could not be calculated for 1 subscale (evaluating the treatment) because of missing data that resulted from patients skipping sections because they had not experienced a symptom. CONCLUSION: Clinicians interested in evaluating the self-management abilities of their patients with heart failure are encouraged to use this tool and to contribute to additional testing
@article{riegel_development_2000,
title = {Development and testing of a clinical tool measuring self-management of heart failure.},
volume = {29},
issn = {0147-9563},
abstract = {BACKGROUND: Self-management is a primary goal of treatment for heart failure. Yet no measure of self-management in this patient group currently exists. OBJECTIVES: To develop a clinically useful measure of the abilities of patients with heart failure to manage their disease. Self-management in this context was defined as a cognitive decision-making process undertaken in response to signs and symptoms of heart failure. A panel of experts agreed that the process involved 4 distinct stages: recognizing a change, evaluating the change, implementing a treatment strategy, and evaluating the treatment. The tool was developed to reflect this process. METHODS: Face validity of the process model was assessed in a sample of 25 patients with heart failure and used to develop a 65-item tool with 6 subscales. The subscales measure the 4 stages as well as the patients' ease in evaluating the signs and symptoms and their self-efficacy. The tool was pilot tested with 2 samples of patients with heart failure (N = 17; N = 129). Psychometrics of the final tool were then tested in a sample of 127 patients with heart failure. RESULTS: Face and content validity of the tool were demonstrated adequately through this study. Internal consistency scores of the 6 subscales of the Self-Management of Heart Failure instrument ranged from 0.79 (ease of evaluating treatment) to 0.92 (evaluating the change). Reliability could not be calculated for 1 subscale (evaluating the treatment) because of missing data that resulted from patients skipping sections because they had not experienced a symptom. CONCLUSION: Clinicians interested in evaluating the self-management abilities of their patients with heart failure are encouraged to use this tool and to contribute to additional testing},
number = {1},
journal = {Heart Lung},
author = {Riegel, B. and Carlson, B. and Glaser, D.},
year = {2000},
keywords = {3D proceso validación, Aged, Evaluation Studies as Topic, Female, Heart Failure, Humans, Male, Middle Aged, Pilot Projects, Psychometrics, Reproducibility of Results, Self Care, content validity, non-u.s. gov't, research support, validity, validity \& reliability},
pages = {4--15}
}On the genealogy of a sample of neutral rare alleles. Wiuf, C. Theor Popul Biol, 58(1):61-75., 2000.
abstract bibtex
abstract bibtex
This paper concerns the genealogical structure of a sample of chromosomes sharing a neutral rare allele. We suppose that the mutation giving rise to the allele has only happened once in the history of the entire population, and that the allele is of known frequency q in the population. Within a coalescent framework C. Wiuf and P. Donnelly (1999, Theor. Popul. Biol. 56, 183-201) derived an exact analysis of the conditional genealogy but it is inconvenient for applications. Here, we develop an approximation to the exact distribution of the conditional genealogy, including an approximation to the distribution of the time at which the mutation arose. The approximations are accurate for frequencies q<5-10%. In addition, a simple and fast simulation scheme is constructed. We consider a demography parameterized by a d-dimensional vector alpha=(alpha(1), em leader, alpha(d)). It is shown that the conditional genealogy and the age of the mutation have distributions that depend on a=qalpha and q only, and that the effect of q is a linear scaling of times in the genealogy; if q is doubled, the lengths of all branches in the genealogy are doubled. The theory is exemplified in two different demographies of some interest in the study of human evolution: (1) a population of constant size and (2) a population of exponentially decreasing size (going backward in time).
@article{
title = {On the genealogy of a sample of neutral rare alleles},
type = {article},
year = {2000},
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pages = {61-75.},
volume = {58},
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abstract = {This paper concerns the genealogical structure of a sample of chromosomes sharing a neutral rare allele. We suppose that the mutation giving rise to the allele has only happened once in the history of the entire population, and that the allele is of known frequency q in the population. Within a coalescent framework C. Wiuf and P. Donnelly (1999, Theor. Popul. Biol. 56, 183-201) derived an exact analysis of the conditional genealogy but it is inconvenient for applications. Here, we develop an approximation to the exact distribution of the conditional genealogy, including an approximation to the distribution of the time at which the mutation arose. The approximations are accurate for frequencies q<5-10%. In addition, a simple and fast simulation scheme is constructed. We consider a demography parameterized by a d-dimensional vector alpha=(alpha(1), em leader, alpha(d)). It is shown that the conditional genealogy and the age of the mutation have distributions that depend on a=qalpha and q only, and that the effect of q is a linear scaling of times in the genealogy; if q is doubled, the lengths of all branches in the genealogy are doubled. The theory is exemplified in two different demographies of some interest in the study of human evolution: (1) a population of constant size and (2) a population of exponentially decreasing size (going backward in time).},
bibtype = {article},
author = {Wiuf, C},
journal = {Theor Popul Biol},
number = {1}
}A short tandem repeat-based phylogeny for the human Y chromosome. Forster, P., Rohl, A., Lunnemann, P., Brinkmann, C., Zerjal, T., Tyler-Smith, C., & Brinkmann, B. Am J Hum Genet, 67(1):182-96., 2000.
Paper abstract bibtex
Paper abstract bibtex Human Y-chromosomal short tandem repeat (STR) data provide a potential model system for the understanding of autosomal STR mutations in humans and other species. Yet, the reconstruction of STR evolution is rarely attempted, because of the absence of an appropriate methodology. We here develop and validate a phylogenetic-network approach. We have typed 256 Y chromosomes of indigenous descent from Africa, Asia, Europe, Australia, and highland Papua New Guinea, for the STR loci DYS19, DXYS156Y, DYS389, DYS390, DYS392, and DYS393, as well as for five ancient biallelic mutation events: two poly (A) length variants associated with the YAP insertion, two independent SRY-1532 mutations, and the 92R7 mutation. We have used our previously published pedigree data from 11,000 paternity-tested autosomal STR-allele transfers to produce a two-class weighting system for the Y-STR loci that is based on locus lengths and motif lengths. Reduced-median-network analysis yields a phylogeny that is independently supported by the five biallelic mutations, with an error of 6%. We find the earliest branch in our African San (Bushmen) sample. Assuming an age of 20,000 years for the Native American DYS199 T mutation, we estimate a mutation rate of 2.6x10-4 mutations/20 years for slowly mutating Y STRs, approximately 10-fold slower than the published average pedigree rate.
@article{
title = {A short tandem repeat-based phylogeny for the human Y chromosome},
type = {article},
year = {2000},
identifiers = {[object Object]},
keywords = {*Phylogeny,Africa,Alleles,Asia,Australia,Calibration,Ethnic Groups/genetics,Europe,Evolution, Molecular,Genetic Markers/genetics,Human,Kinetics,Male,Mutation/genetics,Papua New Guinea,Polymorphism (Genetics)/genetics,Racial Stocks/genetics,Sensitivity and Specificity,Support, Non-U.S. Gov't,Tandem Repeat Sequences/*genetics,Time Factors,Y Chromosome/*genetics},
pages = {182-96.},
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abstract = {Human Y-chromosomal short tandem repeat (STR) data provide a potential model system for the understanding of autosomal STR mutations in humans and other species. Yet, the reconstruction of STR evolution is rarely attempted, because of the absence of an appropriate methodology. We here develop and validate a phylogenetic-network approach. We have typed 256 Y chromosomes of indigenous descent from Africa, Asia, Europe, Australia, and highland Papua New Guinea, for the STR loci DYS19, DXYS156Y, DYS389, DYS390, DYS392, and DYS393, as well as for five ancient biallelic mutation events: two poly (A) length variants associated with the YAP insertion, two independent SRY-1532 mutations, and the 92R7 mutation. We have used our previously published pedigree data from 11,000 paternity-tested autosomal STR-allele transfers to produce a two-class weighting system for the Y-STR loci that is based on locus lengths and motif lengths. Reduced-median-network analysis yields a phylogeny that is independently supported by the five biallelic mutations, with an error of 6%. We find the earliest branch in our African San (Bushmen) sample. Assuming an age of 20,000 years for the Native American DYS199 T mutation, we estimate a mutation rate of 2.6x10-4 mutations/20 years for slowly mutating Y STRs, approximately 10-fold slower than the published average pedigree rate.},
bibtype = {article},
author = {Forster, P and Rohl, A and Lunnemann, P and Brinkmann, C and Zerjal, T and Tyler-Smith, C and Brinkmann, B},
journal = {Am J Hum Genet},
number = {1}
}1999 (3)
Unique PABP2 mutations in "Cajuns" suggest multiple founders of oculopharyngeal muscular dystrophy in populations with French ancestry. Scacheri, P., C., Garcia, C., Hébert, R., Hoffman, E., P., & Hebert, R. Am J Med Genet, 86(5):477-481, 10, 1999.
Paper Website abstract bibtex
Paper Website abstract bibtex Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant myopathy found world-wide, but with the highest incidence in French-Canadians. Short GCG expansions in the poly(A) binding protein 2 (PABP2) gene were identified recently as the molecular basis for OPMD in French-Canadians. All French-Canadian cases of OPMD have been traced to a single founder couple [Bouchard, 1997: Neuromuscul Disord 7(Suppl):S5-S11]. Cultural links between French-Canadians and Cajuns suggest that this same founder couple may have transmitted the OPMD mutation to Cajuns as well. To determine if OPMD patients from Louisiana share a founder effect with French-Canadian families, we collected blood samples and muscle biopsies from several Cajuns with OPMD for mutation and linkage studies. We found a unique 'GCA GCG GCG' insertion mutation in Cajuns. Consistent with these sequence data, we identified a disease haplotype in our Cajun families that is different from the ancestral haplotype defined in French-Canadians. These data prove that different founders introduced the PABP2 mutation to Cajuns and French-Canadians and lend support to emerging genealogical data suggesting that French-Canadians and Cajuns represent distinct immigrant groups from France.
@article{
title = {Unique PABP2 mutations in "Cajuns" suggest multiple founders of oculopharyngeal muscular dystrophy in populations with French ancestry},
type = {article},
year = {1999},
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pages = {477-481},
volume = {86},
websites = {http://www.ncbi.nlm.nih.gov/pubmed/10508991},
month = {10},
day = {29},
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notes = {<m:note> <m:bold>From Duplicate 1 ( </m:bold> <m:bold> </m:bold><m:bold><m:italic>Unique PABP2 mutations in "Cajuns" suggest multiple founders of oculopharyngeal muscular dystrophy in populations with French ancestry</m:italic></m:bold><m:bold> </m:bold> <m:bold> - Scacheri, P C; Garcia, C; Hebert, R; Hoffman, E P )<m:linebreak/> </m:bold> <m:linebreak/>Journal Article<m:linebreak/> <m:linebreak/> </m:note>},
abstract = {Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant myopathy found world-wide, but with the highest incidence in French-Canadians. Short GCG expansions in the poly(A) binding protein 2 (PABP2) gene were identified recently as the molecular basis for OPMD in French-Canadians. All French-Canadian cases of OPMD have been traced to a single founder couple [Bouchard, 1997: Neuromuscul Disord 7(Suppl):S5-S11]. Cultural links between French-Canadians and Cajuns suggest that this same founder couple may have transmitted the OPMD mutation to Cajuns as well. To determine if OPMD patients from Louisiana share a founder effect with French-Canadian families, we collected blood samples and muscle biopsies from several Cajuns with OPMD for mutation and linkage studies. We found a unique 'GCA GCG GCG' insertion mutation in Cajuns. Consistent with these sequence data, we identified a disease haplotype in our Cajun families that is different from the ancestral haplotype defined in French-Canadians. These data prove that different founders introduced the PABP2 mutation to Cajuns and French-Canadians and lend support to emerging genealogical data suggesting that French-Canadians and Cajuns represent distinct immigrant groups from France.},
bibtype = {article},
author = {Scacheri, P C and Garcia, C and Hébert, R and Hoffman, E P and Hebert, R},
journal = {Am J Med Genet},
number = {5}
}Use of unlinked genetic markers to detect population stratification in association studies. Pritchard, J., K. & Rosenberg, N., A. Am J Hum Genet, 65(1):220-8., 1999.
Paper abstract bibtex
Paper abstract bibtex We examine the issue of population stratification in association-mapping studies. In case-control studies of association, population subdivision or recent admixture of populations can lead to spurious associations between a phenotype and unlinked candidate loci. Using a model of sampling from a structured population, we show that if population stratification exists, it can be detected by use of unlinked marker loci. We show that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification. We suggest guidelines as to the number of unlinked marker loci to use.
@article{
title = {Use of unlinked genetic markers to detect population stratification in association studies},
type = {article},
year = {1999},
identifiers = {[object Object]},
keywords = {*Case-Control Studies,*Genetic Markers,*Linkage (Genetics),*Models, Genetic,Alleles,Genotype,Human,Research Design,Support, Non-U.S. Gov't,Support, U.S. Gov't, P.H.S.},
pages = {220-8.},
volume = {65},
id = {b79d206a-a398-3b9a-8ad4-7f1e22c70cda},
created = {2017-06-19T13:45:20.473Z},
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abstract = {We examine the issue of population stratification in association-mapping studies. In case-control studies of association, population subdivision or recent admixture of populations can lead to spurious associations between a phenotype and unlinked candidate loci. Using a model of sampling from a structured population, we show that if population stratification exists, it can be detected by use of unlinked marker loci. We show that the case-control-study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate locus are included in the study, to test for stratification. We suggest guidelines as to the number of unlinked marker loci to use.},
bibtype = {article},
author = {Pritchard, J K and Rosenberg, N A},
journal = {Am J Hum Genet},
number = {1}
}Location score and haplotype analyses of the locus for autosomal recessive spastic ataxia of Charlevoix-Saguenay, in chromosome region 13q11. Richter, A., Rioux, J., D., Bouchard, J., P., Mercier, J., Mathieu, J., Ge, B., Poirier, J., Julien, D., Gyapay, G., Weissenbach, J., Hudson, T., J., Melancon, S., B., & Morgan, K. Am J Hum Genet, 64(3):768-775, 1999.
Paper abstract bibtex
Paper abstract bibtex Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogeneous form of early-onset familial spastic ataxia with prominent myelinated retinal nerve fibers. More than 300 patients have been identified, and most of their families originated in the Charlevoix-Saguenay region of northeastern Quebec, where the carrier prevalence has been estimated to be 1/22. Consistent with the hypothesis of a founder effect, we observed excess shared homozygosity at 13q11, among patients in a genomewide scan of 12 families. Analysis of 19 pedigrees demonstrated very tight linkage between the ARSACS locus and an intragenic polymorphism of the gamma-sarcoglycan (SGCG) gene, but genomic DNA sequence analysis of all eight exons of SGCG revealed no disease-causing mutation. On the basis of haplotypes composed of seven marker loci that spanned 11.1 cM, the most likely position of the ARSACS locus was 0.42 cM distal to the SGCG polymorphism. Two groups of ARSACS-associated haplotypes were identified: a large group that carries a common SGCG allele and a small group that carries a rare SGCG allele. The haplotype groups do not appear to be closely related. Therefore, although chromosomes within each haplotype group may harbor a single ARSACS mutation identical by descent, the two mutations could have independent origins.
@article{
title = {Location score and haplotype analyses of the locus for autosomal recessive spastic ataxia of Charlevoix-Saguenay, in chromosome region 13q11},
type = {article},
year = {1999},
identifiers = {[object Object]},
keywords = {Alleles,Chromosomes, Human, Pair 13/*genetics,Cytoskeletal Proteins/genetics,DNA Mutational Analysis,Databases, Factual,Exons,Founder Effect,Genotype,Haplotypes,Human,Linkage (Genetics),Lod Score,Membrane Glycoproteins/genetics,Microsatellite Repeats,Point Mutation,Polymorphism (Genetics),Quebec,Spinocerebellar Degenerations/*etiology/*genetics,Support, Non-U.S. Gov't,Syndrome},
pages = {768-775},
volume = {64},
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abstract = {Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a clinically homogeneous form of early-onset familial spastic ataxia with prominent myelinated retinal nerve fibers. More than 300 patients have been identified, and most of their families originated in the Charlevoix-Saguenay region of northeastern Quebec, where the carrier prevalence has been estimated to be 1/22. Consistent with the hypothesis of a founder effect, we observed excess shared homozygosity at 13q11, among patients in a genomewide scan of 12 families. Analysis of 19 pedigrees demonstrated very tight linkage between the ARSACS locus and an intragenic polymorphism of the gamma-sarcoglycan (SGCG) gene, but genomic DNA sequence analysis of all eight exons of SGCG revealed no disease-causing mutation. On the basis of haplotypes composed of seven marker loci that spanned 11.1 cM, the most likely position of the ARSACS locus was 0.42 cM distal to the SGCG polymorphism. Two groups of ARSACS-associated haplotypes were identified: a large group that carries a common SGCG allele and a small group that carries a rare SGCG allele. The haplotype groups do not appear to be closely related. Therefore, although chromosomes within each haplotype group may harbor a single ARSACS mutation identical by descent, the two mutations could have independent origins.},
bibtype = {article},
author = {Richter, A and Rioux, J D and Bouchard, J P and Mercier, J and Mathieu, J and Ge, B and Poirier, J and Julien, D and Gyapay, G and Weissenbach, J and Hudson, T J and Melancon, S B and Morgan, K},
journal = {Am J Hum Genet},
number = {3}
}1998 (6)
Isonymy and the genetic structure of Switzerland. II. Isolation by distance. Rodriguez-Larralde, A., Scapoli, C., Beretta, M., Nesti, C., Mamolini, E., & Barrai, I. Ann Hum Biol, 25(6):533-40., 1998.
abstract bibtex
abstract bibtex
Isolation by distance in Switzerland was detected comparing the surname distributions between Cantons. The decay of isonymy with geographic distance between Cantons was consistent with Malecot's exponential decay of kinship. Lasker's distance was defined as the negative value of the logarithm of isonymy between localities, and it was found that it is linearly and significantly correlated with the log of geographic distance, both within and between languages. The peculiar geographic and linguistic structure of the Confederation, where mountain barriers exist at short distances separating different languages, might explain the rapid changes in surname similarity. It was predicted that the frequency of markers linked to the Y chromosome would show a similar association with distance in Switzerland.
@article{
title = {Isonymy and the genetic structure of Switzerland. II. Isolation by distance},
type = {article},
year = {1998},
identifiers = {[object Object]},
keywords = {*Genetics, Population,*Names,Human,Support, Non-U.S. Gov't,Switzerland},
pages = {533-40.},
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abstract = {Isolation by distance in Switzerland was detected comparing the surname distributions between Cantons. The decay of isonymy with geographic distance between Cantons was consistent with Malecot's exponential decay of kinship. Lasker's distance was defined as the negative value of the logarithm of isonymy between localities, and it was found that it is linearly and significantly correlated with the log of geographic distance, both within and between languages. The peculiar geographic and linguistic structure of the Confederation, where mountain barriers exist at short distances separating different languages, might explain the rapid changes in surname similarity. It was predicted that the frequency of markers linked to the Y chromosome would show a similar association with distance in Switzerland.},
bibtype = {article},
author = {Rodriguez-Larralde, A and Scapoli, C and Beretta, M and Nesti, C and Mamolini, E and Barrai, I},
journal = {Ann Hum Biol},
number = {6}
}How heritable is individual susceptibility to death? The results of an analysis of survival data on Danish, Swedish and Finnish twins. Iachine, I., A., Holm, N., V., Harris, J., R., Begun, A., Z., Iachina, M., K., Laitinen, M., Kaprio, J., & Yashin, A., I. Twin Res, 1(4):196-205, 1998.
Website abstract bibtex
Website abstract bibtex Molecular epidemiological studies confirm a substantial contribution of individual genes to variability in susceptibility to disease and death for humans. To evaluate the contribution of all genes to susceptibility and to estimate individual survival characteristics, survival data on related individuals (eg twins or other relatives) are needed. Correlated gamma-frailty models of bivariate survival are used in a joint analysis of survival data on more than 31,000 pairs of Danish, Swedish and Finnish male and female twins using the maximum likelihood method. Additive decomposition of frailty into genetic and environmental components is used to estimate heritability in frailty. The estimate of the standard deviation of frailty from the pooled data is about 1.5. The hypothesis that variance in frailty and correlations of frailty for twins are similar in the data from all three countries is accepted. The estimate of narrow-sense heritability in frailty is about 0.5. The age trajectories of individual hazards are evaluated for all three populations of twins and both sexes. The results of our analysis confirm the presence of genetic influences on individual frailty and longevity. They also suggest that the mechanism of these genetic influences may be similar for the three Scandinavian countries. Furthermore, results indicate that the increase in individual hazard with age is more rapid than predicted by traditional demographic life tables.
@article{
title = {How heritable is individual susceptibility to death? The results of an analysis of survival data on Danish, Swedish and Finnish twins},
type = {article},
year = {1998},
identifiers = {[object Object]},
keywords = {*Death,*Genetic Predisposition to Disease,Adult,Age Factors,Aged,Aged, 80 and over,Denmark,Disease Susceptibility,Environment,Epidemiology, Molecular,Female,Finland,Forecasting,Health,Humans,Life Tables,Likelihood Functions,Longevity/genetics,Male,Middle Aged,Models, Genetic,Research Support, Non-U.S. Gov't,Research Support, U.S. Gov't, P.H.S.,Sex Factors,Survival Analysis,Sweden,Twins/*genetics},
pages = {196-205},
volume = {1},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10100811},
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notes = {<m:note>1369-0523<m:linebreak/>Journal Article<m:linebreak/>Twin Study</m:note>},
abstract = {Molecular epidemiological studies confirm a substantial contribution of individual genes to variability in susceptibility to disease and death for humans. To evaluate the contribution of all genes to susceptibility and to estimate individual survival characteristics, survival data on related individuals (eg twins or other relatives) are needed. Correlated gamma-frailty models of bivariate survival are used in a joint analysis of survival data on more than 31,000 pairs of Danish, Swedish and Finnish male and female twins using the maximum likelihood method. Additive decomposition of frailty into genetic and environmental components is used to estimate heritability in frailty. The estimate of the standard deviation of frailty from the pooled data is about 1.5. The hypothesis that variance in frailty and correlations of frailty for twins are similar in the data from all three countries is accepted. The estimate of narrow-sense heritability in frailty is about 0.5. The age trajectories of individual hazards are evaluated for all three populations of twins and both sexes. The results of our analysis confirm the presence of genetic influences on individual frailty and longevity. They also suggest that the mechanism of these genetic influences may be similar for the three Scandinavian countries. Furthermore, results indicate that the increase in individual hazard with age is more rapid than predicted by traditional demographic life tables.},
bibtype = {article},
author = {Iachine, I A and Holm, N V and Harris, J R and Begun, A Z and Iachina, M K and Laitinen, M and Kaprio, J and Yashin, A I},
journal = {Twin Res},
number = {4}
}Factors affecting population variation in eastern Adriatic isolates (Croatia). Waddle, D., M., Sokal, R., R., & Rudan, P. Hum Biol, 70(5):845-64., 1998.
abstract bibtex
abstract bibtex
Inhabitants of the Croatian islands of Brac, Hvar, Korcula, and the Peljesac Peninsula have been the subject of extensive previous studies of local population differentiation. Most of these studies used biological and ecological variables, but some also considered historical and sociological factors. In this study we use genetic, morphological, kinship, and language distance data, collected for individuals from 26 rural communities on the islands of Brac, Hvar, Korcula, and the Peljesac Peninsula in the Adriatic, to further explore the interaction of historical, sociological, and biological factors in small populations and to test the significance of some of these proposed causes. First, we use matrix correlation methods to evaluate the relationships among different types of distance measures. The specific measures of genetic distance used here do not correlate well with other measures of population distance, and it appears that for the studied genetic systems the populations are not strongly differentiated. As expected, kinship and language distances have a high degree of association. Morphological differences among populations seem to be more closely tied to kinship distances than to genetic distances. This may result from modification of some morphological features by environmental rather than genetic factors, or it may be attributed to extensive, selective, nonrandom emigration of the population during the first decade of the twentieth century. In the second part of our analysis we use matrix correlation methods to evaluate and possibly identify the external factors that have contributed to the population differences. Specifically, we use design matrices to test hypotheses that population differences can be explained by one of the following factors: geographic isolation on the islands and peninsula, distance from the mainland, geographic barriers within the islands and peninsula, and the historical factors that differentially affected the three islands and the peninsula. Most of these design matrices reflect geographic distances; although correlations between morphological variables and simple geographic distance between localities were not significant, correlations between these localities and a design matrix incorporating geographic distance along with geographic barriers, such as bodies of water and mountain ranges, are particularly important for explaining distances among kin. Design matrices provide an important tool for quantifying the relationship between historical and geographic factors, and measures of population distance.
@article{
title = {Factors affecting population variation in eastern Adriatic isolates (Croatia)},
type = {article},
year = {1998},
identifiers = {[object Object]},
keywords = {*Genetics, Population,*Population Dynamics,Anthropometry,Croatia,Family Characteristics,Female,Human,Linguistics,Male,Phenotype,Support, Non-U.S. Gov't,Support, U.S. Gov't, Non-P.H.S.},
pages = {845-64.},
volume = {70},
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abstract = {Inhabitants of the Croatian islands of Brac, Hvar, Korcula, and the Peljesac Peninsula have been the subject of extensive previous studies of local population differentiation. Most of these studies used biological and ecological variables, but some also considered historical and sociological factors. In this study we use genetic, morphological, kinship, and language distance data, collected for individuals from 26 rural communities on the islands of Brac, Hvar, Korcula, and the Peljesac Peninsula in the Adriatic, to further explore the interaction of historical, sociological, and biological factors in small populations and to test the significance of some of these proposed causes. First, we use matrix correlation methods to evaluate the relationships among different types of distance measures. The specific measures of genetic distance used here do not correlate well with other measures of population distance, and it appears that for the studied genetic systems the populations are not strongly differentiated. As expected, kinship and language distances have a high degree of association. Morphological differences among populations seem to be more closely tied to kinship distances than to genetic distances. This may result from modification of some morphological features by environmental rather than genetic factors, or it may be attributed to extensive, selective, nonrandom emigration of the population during the first decade of the twentieth century. In the second part of our analysis we use matrix correlation methods to evaluate and possibly identify the external factors that have contributed to the population differences. Specifically, we use design matrices to test hypotheses that population differences can be explained by one of the following factors: geographic isolation on the islands and peninsula, distance from the mainland, geographic barriers within the islands and peninsula, and the historical factors that differentially affected the three islands and the peninsula. Most of these design matrices reflect geographic distances; although correlations between morphological variables and simple geographic distance between localities were not significant, correlations between these localities and a design matrix incorporating geographic distance along with geographic barriers, such as bodies of water and mountain ranges, are particularly important for explaining distances among kin. Design matrices provide an important tool for quantifying the relationship between historical and geographic factors, and measures of population distance.},
bibtype = {article},
author = {Waddle, D M and Sokal, R R and Rudan, P},
journal = {Hum Biol},
number = {5}
}Selective attention: a reevaluation of the implications of negative priming. Milliken, B., Joordens, S., Merikle, P., & Seiffert, A. Psychological Review, 105(2):203–229, 1998.
doi abstract bibtex
doi abstract bibtex
The notion that inhibitory processes play a critical role in selective attention has gained wide support. Much of this support derives from studies of negative priming. The authors note that the attribution of negative priming to an inhibitory mechanism of attention draws its support from a common assumption underlying priming procedures, together with the procedure that has been used to measure negative priming. The results from a series of experiments demonstrate that selection between 2 competing prime items is not required to observe negative priming. This result is demonstrated across several experiments in which participants named 1 of 2 items in a second display following presentation of a single-item prime. The implications of these results for existing theories of negative priming are discussed, and a theoretical framework for interpreting negative priming and several related phenomena is forwarded.
@article{milliken_selective_1998,
title = {Selective attention: a reevaluation of the implications of negative priming},
volume = {105},
doi = {10/b5xt6q},
abstract = {The notion that inhibitory processes play a critical role in selective attention has gained wide support. Much of this support derives from studies of negative priming. The authors note that the attribution of negative priming to an inhibitory mechanism of attention draws its support from a common assumption underlying priming procedures, together with the procedure that has been used to measure negative priming. The results from a series of experiments demonstrate that selection between 2 competing prime items is not required to observe negative priming. This result is demonstrated across several experiments in which participants named 1 of 2 items in a second display following presentation of a single-item prime. The implications of these results for existing theories of negative priming are discussed, and a theoretical framework for interpreting negative priming and several related phenomena is forwarded.},
number = {2},
journal = {Psychological Review},
author = {Milliken, B. and Joordens, S. and Merikle, P.M. and Seiffert, A.E.},
year = {1998},
keywords = {\#nosource, *Cues, *Inhibition (Psychology), Adult, Analysis of Variance, Attention/*physiology, Female, Human, Male, Reading, Support, Non-U.S. Gov't, Volition/*physiology},
pages = {203--229},
}Mapping genes through the use of linkage disequilibrium generated by genetic drift: 'drift mapping' in small populations with no demographic expansion. Terwilliger, J., D., Zollner, S., Laan, M., & Paabo, S. Hum Hered, 48(3):138-54., 1998.
Paper abstract bibtex
Paper abstract bibtex Linkage disequilibrium has been a powerful tool in identifying rare disease alleles in human populations. To date, most research has been directed to isolated populations which have undergone a bottleneck followed by rapid exponential expansion. While this strategy works well for rare diseases in which all disease alleles in the population today are clonal copies of some common ancestral allele, for common disease genes with substantial allelic heterogeneity, this approach is not predicted to work. In this paper, we describe the dynamics of linkage disequilibrium in populations which have not undergone a demographic expansion. In these populations, it is shown that genetic drift creates disequilibrium over time, while in expanded populations, the disequilibrium decays with time. We propose that common disease alleles might be more efficiently identified by drift mapping - linkage disequilibrium mapping in small, old populations of constant size where the disequilibrium is the result of genetic drift, not founder effect. Theoretical models, empirical data, and simulated population models are presented as evidence for the utility of this approach.
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title = {Mapping genes through the use of linkage disequilibrium generated by genetic drift: 'drift mapping' in small populations with no demographic expansion},
type = {article},
year = {1998},
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pages = {138-54.},
volume = {48},
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abstract = {Linkage disequilibrium has been a powerful tool in identifying rare disease alleles in human populations. To date, most research has been directed to isolated populations which have undergone a bottleneck followed by rapid exponential expansion. While this strategy works well for rare diseases in which all disease alleles in the population today are clonal copies of some common ancestral allele, for common disease genes with substantial allelic heterogeneity, this approach is not predicted to work. In this paper, we describe the dynamics of linkage disequilibrium in populations which have not undergone a demographic expansion. In these populations, it is shown that genetic drift creates disequilibrium over time, while in expanded populations, the disequilibrium decays with time. We propose that common disease alleles might be more efficiently identified by drift mapping - linkage disequilibrium mapping in small, old populations of constant size where the disequilibrium is the result of genetic drift, not founder effect. Theoretical models, empirical data, and simulated population models are presented as evidence for the utility of this approach.},
bibtype = {article},
author = {Terwilliger, J D and Zollner, S and Laan, M and Paabo, S},
journal = {Hum Hered},
number = {3}
}A genome scan for loci influencing total serum immunoglobulin levels: possible linkage of IgA to the chromosome 13 atopy locus. Wiltshire, S., Bhattacharyya, S., Faux, J., A., Leaves, N., I., Daniels, S., E., Moffatt, M., F., James, A., Musk, A., W., & Cookson, W., O. Hum Mol Genet, 7(1):27-31, 1998.
Website abstract bibtex
Website abstract bibtex Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE levels. In this study, 80 nuclear families have been examined for linkage of total serum IgA, IgG and IgM levels to a genome-wide panel of microsatellite markers. Potential quantitative trait loci influencing IgA levels have been identified on chromosomes 10 and 13, and possible loci influencing IgG levels were found on chromosomes 3 and 13. No significant linkages to IgM levels were found. The linkage of IgA on chromosome 13 was to a marker previously linked to IgE responses (atopy). Linkage to IgG was in the same region but to a more distal marker. None of the factors known to influence immunoglobulin expression map to the loci identified in the present study. These loci are therefore likely to contain previously unrecognized components of the immunoregulatory system.
@article{
title = {A genome scan for loci influencing total serum immunoglobulin levels: possible linkage of IgA to the chromosome 13 atopy locus},
type = {article},
year = {1998},
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pages = {27-31},
volume = {7},
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abstract = {Immunoglobulins play an essential part in the immune system, and immunoglobulin deficiencies can have profound medical consequences. The genetic control and regulation of the immunoglobulin response is therefore of interest. Previous investigations have identified a number of loci influencing total and specific IgE levels. In this study, 80 nuclear families have been examined for linkage of total serum IgA, IgG and IgM levels to a genome-wide panel of microsatellite markers. Potential quantitative trait loci influencing IgA levels have been identified on chromosomes 10 and 13, and possible loci influencing IgG levels were found on chromosomes 3 and 13. No significant linkages to IgM levels were found. The linkage of IgA on chromosome 13 was to a marker previously linked to IgE responses (atopy). Linkage to IgG was in the same region but to a more distal marker. None of the factors known to influence immunoglobulin expression map to the loci identified in the present study. These loci are therefore likely to contain previously unrecognized components of the immunoregulatory system.},
bibtype = {article},
author = {Wiltshire, S and Bhattacharyya, S and Faux, J A and Leaves, N I and Daniels, S E and Moffatt, M F and James, A and Musk, A W and Cookson, W O},
journal = {Hum Mol Genet},
number = {1}
}1997 (4)
Neural mechanisms of spatial selective attention in areas V1, V2, and V4 of macaque visual cortex. Luck, S J, Chelazzi, L, Hillyard, S A, & Desimone, R J Neurophysiol, 77(1):24–42, 1997. Place: UNITED STATES ISBN: 0022-3077
abstract bibtex
abstract bibtex
Many neurons in extrastriate visual cortex have large receptive fields, and this may lead to significant computational problems whenever multiple stimuli fall within a single field. Previous studies have suggested that when multiple stimuli fall within a cell's receptive field, they compete for the cell's response in a manner that can be biased in favor of attended stimuli. In the present study we examined this role of attention in areas V1, V2, and V4 of macaque monkeys with the use of a behavioral paradigm in which attention was directed to one of two stimulus locations. When two stimuli were presented simultaneously inside the cell's receptive field (which could be accomplished only in areas V2 and V4), we found that the cell's response was strongly influenced by which of the two stimuli was attended. The size of this attention effect was reduced when the attended and ignored stimuli were presented sequentially rather than simultaneously. In addition, the effects became very weak and inconsistent in these areas when only one of the two stimuli was located inside the receptive field. Attention thus modulated sensory responses primarily when two or more simultaneous stimuli competed for access to a neuron's receptive field. As in areas V2 and V4, attention did not modulate sensory responses in area V1 when only a single stimulus was inside the receptive field. In addition, the small receptive fields in this area precluded the simultaneous presentation of attended and ignored stimuli inside the receptive field, making it impossible to determine whether attention effects would be observed under the conditions that led to consistent attention effects in areas V2 and V4. Spontaneous firing rates in areas V2 and V4 were found to be 30-40% higher when attention was directed inside rather than outside the receptive field, even when no stimulus was present in the receptive field. Spontaneous firing rates also varied according to the particular location within the receptive field that was attended. These shifts in spontaneous activity may reflect a top-down signal that biases responses in favor of stimuli at the attended location.
@article{luck_neural_1997,
title = {Neural mechanisms of spatial selective attention in areas {V1}, {V2}, and {V4} of macaque visual cortex.},
volume = {77},
abstract = {Many neurons in extrastriate visual cortex have large receptive fields, and this may lead to significant computational problems whenever multiple stimuli fall within a single field. Previous studies have suggested that when multiple stimuli fall within a cell's receptive field, they compete for the cell's response in a manner that can be biased in favor of attended stimuli. In the present study we examined this role of attention in areas V1, V2, and V4 of macaque monkeys with the use of a behavioral paradigm in which attention was directed to one of two stimulus locations. When two stimuli were presented simultaneously inside the cell's receptive field (which could be accomplished only in areas V2 and V4), we found that the cell's response was strongly influenced by which of the two stimuli was attended. The size of this attention effect was reduced when the attended and ignored stimuli were presented sequentially rather than simultaneously. In addition, the effects became very weak and inconsistent in these areas when only one of the two stimuli was located inside the receptive field. Attention thus modulated sensory responses primarily when two or more simultaneous stimuli competed for access to a neuron's receptive field. As in areas V2 and V4, attention did not modulate sensory responses in area V1 when only a single stimulus was inside the receptive field. In addition, the small receptive fields in this area precluded the simultaneous presentation of attended and ignored stimuli inside the receptive field, making it impossible to determine whether attention effects would be observed under the conditions that led to consistent attention effects in areas V2 and V4. Spontaneous firing rates in areas V2 and V4 were found to be 30-40\% higher when attention was directed inside rather than outside the receptive field, even when no stimulus was present in the receptive field. Spontaneous firing rates also varied according to the particular location within the receptive field that was attended. These shifts in spontaneous activity may reflect a top-down signal that biases responses in favor of stimuli at the attended location.},
language = {eng},
number = {1},
journal = {J Neurophysiol},
author = {Luck, S J and Chelazzi, L and Hillyard, S A and Desimone, R},
year = {1997},
pmid = {9120566},
note = {Place: UNITED STATES
ISBN: 0022-3077},
keywords = {Animals, Attention, Cues, Electrodes, Implanted, Evoked Potentials, Visual, Eye Movements, Macaca mulatta, Male, Neurons, Photic Stimulation, Psychomotor Performance, Space Perception, Visual Cortex, research support, non-u.s. gov't, research support, u.s. gov't, non-p.h.s., research support, u.s. gov't, p.h.s.},
pages = {24--42},
}Genetics of aging. Finch, C., E. & Tanzi, R., E. Science, 278(5337):407-411, 1997.
Website abstract bibtex
Website abstract bibtex The role of genetics in determining life-span is complex and paradoxical. Although the heritability of life-span is relatively minor, some genetic variants significantly modify senescence of mammals and invertebrates, with both positive and negative impacts on age-related disorders and life-spans. In certain examples, the gene variants alter metabolic pathways, which could thereby mediate interactions with nutritional and other environmental factors that influence life-span. Given the relatively minor effect and variable penetrance of genetic risk factors that appear to affect survival and health at advanced ages, life-style and other environmental influences may profoundly modify outcomes of aging.
@article{
title = {Genetics of aging},
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pages = {407-411},
volume = {278},
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abstract = {The role of genetics in determining life-span is complex and paradoxical. Although the heritability of life-span is relatively minor, some genetic variants significantly modify senescence of mammals and invertebrates, with both positive and negative impacts on age-related disorders and life-spans. In certain examples, the gene variants alter metabolic pathways, which could thereby mediate interactions with nutritional and other environmental factors that influence life-span. Given the relatively minor effect and variable penetrance of genetic risk factors that appear to affect survival and health at advanced ages, life-style and other environmental influences may profoundly modify outcomes of aging.},
bibtype = {article},
author = {Finch, C E and Tanzi, R E},
journal = {Science},
number = {5337}
}Atopic dermatitis and birth factors: historical follow up by record linkage. Olesen, A., B., Ellingsen, A., R., Olesen, H., Juul, S., & Thestrup-Pedersen, K. Bmj, 314(7086):1003-1008, 1997.
Website abstract bibtex
Website abstract bibtex OBJECTIVE: To study if factors at birth are associated with later development of atopic dermatitis. DESIGN: Historical follow up by record linkage from Danish medical birth register. Children were followed up for 5.5 to 8.5 years. Second historical follow up study comprising questionnaire to mothers of singleborn children 6.5 to 9.5 years after birth. SETTING: Private dermatology clinics and dermatology and paediatric departments in the municipality of Aarhus, Denmark. SUBJECTS: 7862 singletons born in hospital between 1 January 1984 and 31 December 1986 to mothers living in the municipality of Aarhus. Questionnaires sent to 985 mothers. MAIN OUTCOME MEASURES: Gestational age, birth weight, parity, and age of mother at the time of birth. Atopy in children diagnosed by specialists in dermatology and physicians. Family size; diagnosis of atopic dermatitis, allergic rhinitis, and asthma; family predisposition; and mothers' smoking habits during pregnancy determined from questionnaires. RESULTS: Of 7862 children, 403 were diagnosed as having atopic dermatitis by a specialist; the cumulative incidence at age 7 was 5.6%. High gestational age and low parity were associated with an increased risk of atopic dermatitis. Among 985 children atopic dermatitis had been diagnosed by any physician in 184; the cumulative incidence at age 7 was 18.7%. High birth weight, high gestational age, and family history of atopy were associated with increased risk of atopic dermatitis. CONCLUSION: In both studies the incidence of atopic dermatitis was associated with high gestational age and in one with high birth weight also. The causes for these associations are at present unknown but may indicate that even during gestation factors associated with atopic dermatitis influence maturation.
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title = {Atopic dermatitis and birth factors: historical follow up by record linkage},
type = {article},
year = {1997},
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pages = {1003-1008},
volume = {314},
websites = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9112844},
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abstract = {OBJECTIVE: To study if factors at birth are associated with later development of atopic dermatitis. DESIGN: Historical follow up by record linkage from Danish medical birth register. Children were followed up for 5.5 to 8.5 years. Second historical follow up study comprising questionnaire to mothers of singleborn children 6.5 to 9.5 years after birth. SETTING: Private dermatology clinics and dermatology and paediatric departments in the municipality of Aarhus, Denmark. SUBJECTS: 7862 singletons born in hospital between 1 January 1984 and 31 December 1986 to mothers living in the municipality of Aarhus. Questionnaires sent to 985 mothers. MAIN OUTCOME MEASURES: Gestational age, birth weight, parity, and age of mother at the time of birth. Atopy in children diagnosed by specialists in dermatology and physicians. Family size; diagnosis of atopic dermatitis, allergic rhinitis, and asthma; family predisposition; and mothers' smoking habits during pregnancy determined from questionnaires. RESULTS: Of 7862 children, 403 were diagnosed as having atopic dermatitis by a specialist; the cumulative incidence at age 7 was 5.6%. High gestational age and low parity were associated with an increased risk of atopic dermatitis. Among 985 children atopic dermatitis had been diagnosed by any physician in 184; the cumulative incidence at age 7 was 18.7%. High birth weight, high gestational age, and family history of atopy were associated with increased risk of atopic dermatitis. CONCLUSION: In both studies the incidence of atopic dermatitis was associated with high gestational age and in one with high birth weight also. The causes for these associations are at present unknown but may indicate that even during gestation factors associated with atopic dermatitis influence maturation.},
bibtype = {article},
author = {Olesen, A B and Ellingsen, A R and Olesen, H and Juul, S and Thestrup-Pedersen, K},
journal = {Bmj},
number = {7086}
}Spatial transformations in the parietal cortex using basis functions. Pouget, A. & Sejnowski, T. Journal of Cognitive Neuroscience, 9(2):222–237, 1997.
doi abstract bibtex
doi abstract bibtex
Sensorimotor transformations are nonlinear mappings of sensory inputs to motor responses. We explore here the possibility that the responses of single neurons in the parietal cortex serve as basis functions for these transformations. Basis function decomposition is a general method for approximating nonlinear functions that is computationally efficient and well suited for adaptive modification. In particular, the responses of single parietal neurons can be approximated by the product of a Gaussian function of retinal location and a sigmoid function of eye position, called a gain field. A large set of such functions forms a basis set that can be used to perform an arbitrary motor response through a direct projection. We compare this hypothesis with other approaches that are commonly used to model population codes, such as computational maps and vectorial representations. Neither of these alternatives can fully account for the responses of parietal neurons, and they are computationally less efficient for nonlinear transformations. Basis functions also have the advantage of not depending on any coordinate system or reference frame. As a consequence, the position of an object can be represented in multiple reference frames simultaneously, a property consistent with the behavior of hemineglect patients with lesions in the parietal cortex.
@article{pouget_spatial_1997,
title = {Spatial transformations in the parietal cortex using basis functions},
volume = {9},
doi = {10/djdwsp},
abstract = {Sensorimotor transformations are nonlinear mappings of sensory inputs to motor responses. We explore here the possibility that the responses of single neurons in the parietal cortex serve as basis functions for these transformations. Basis function decomposition is a general method for approximating nonlinear functions that is computationally efficient and well suited for adaptive modification. In particular, the responses of single parietal neurons can be approximated by the product of a Gaussian function of retinal location and a sigmoid function of eye position, called a gain field. A large set of such functions forms a basis set that can be used to perform an arbitrary motor response through a direct projection. We compare this hypothesis with other approaches that are commonly used to model population codes, such as computational maps and vectorial representations. Neither of these alternatives can fully account for the responses of parietal neurons, and they are computationally less efficient for nonlinear transformations. Basis functions also have the advantage of not depending on any coordinate system or reference frame. As a consequence, the position of an object can be represented in multiple reference frames simultaneously, a property consistent with the behavior of hemineglect patients with lesions in the parietal cortex.},
number = {2},
journal = {Journal of Cognitive Neuroscience},
author = {Pouget, A. and Sejnowski, T.J.},
year = {1997},
keywords = {\#nosource, *Models, Psychological, *Space Perception, Human, Perceptual Disorders/*physiopathology, Recognition (Psychology), Support, Non-U.S. Gov't, Support, U.S. Gov't, Non-P.H.S.},
pages = {222--237},
}1996 (8)
Asthma on Tristan da Cunha: looking for the genetic link. The University of Toronto Genetics of Asthma Research Group. Zamel, N., McClean, P., A., Sandell, P., R., Siminovitch, K., A., & Slutsky, A., S. Am J Respir Crit Care Med, 153(6 Pt 1):1902-1906, 1996.
Website abstract bibtex
Website abstract bibtex Although asthma has a significant heritable component, the mode of inheritance remains controversial because of the complexity of the disease and the influence of environmental factors. Isolated, inbred populations serve to reduce variability, thus increasing the probability of gene localization. We studied the inbred population of the remote island of Tristan da Cunha to document asthma prevalence for the purpose of genetic linkage analysis. Medical histories and skin atopy were determined on 282 islanders, representing 97% of the population, and airway responsiveness was measured in 254; 226 by methacholine challenge (tidal breathing method) and 28 by bronchodilator response (400 micrograms salbutamol aerosol). Blood samples were collected from 275 islanders. Participants ranged in age from 3 to 94 yr. Asthma was defined as increased airway responsiveness (AR+: PC20 < 4 mg/ml or > or = 15% increase in FEV1 postbronchodilator) combined with a positive history (Hx+). Fifty-seven percent of the islanders had at least partial evidence of asthma (Hx+ and/or AR+) and 23% had a definitive diagnosis of asthma (AR+ with Hx+). Overall 47% of the population were atopic, atopy was proportionally higher in asthmatics (74%) than nonasthmatics (32%; p < 0.01). Analysis of the methacholine dose-response curves demonstrated that asthmatics were significantly (p < 0.01) more responsive than those with AR+ only, and nonasthmatics (AR-, Hx-) were more responsive than laboratory control subjects (p < 0.05), suggesting that these islanders may also carry an airway hyperresponsiveness gene. A frequency plot of the percent fall in FEV1 for all Hx- subjects compared with control data suggests a bimodal distribution consistent with a major gene mechanism for airway responsiveness. Genealogy mapping revealed that the islanders are direct descendants of the 15 original settlers, and historical records suggest at least two founders may have been asthmatic. The data confirm previous reports of a high asthma prevalence on Tristan and support the postulate that this prevalence is a result of gene enrichment occurring in isolated populations by virtue of extensive inbreeding and a probable founder effect.
@article{
title = {Asthma on Tristan da Cunha: looking for the genetic link. The University of Toronto Genetics of Asthma Research Group},
type = {article},
year = {1996},
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pages = {1902-1906},
volume = {153},
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hidden = {false},
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notes = {<m:note>1073-449x<m:linebreak/>Journal Article</m:note>},
abstract = {Although asthma has a significant heritable component, the mode of inheritance remains controversial because of the complexity of the disease and the influence of environmental factors. Isolated, inbred populations serve to reduce variability, thus increasing the probability of gene localization. We studied the inbred population of the remote island of Tristan da Cunha to document asthma prevalence for the purpose of genetic linkage analysis. Medical histories and skin atopy were determined on 282 islanders, representing 97% of the population, and airway responsiveness was measured in 254; 226 by methacholine challenge (tidal breathing method) and 28 by bronchodilator response (400 micrograms salbutamol aerosol). Blood samples were collected from 275 islanders. Participants ranged in age from 3 to 94 yr. Asthma was defined as increased airway responsiveness (AR+: PC20 < 4 mg/ml or > or = 15% increase in FEV1 postbronchodilator) combined with a positive history (Hx+). Fifty-seven percent of the islanders had at least partial evidence of asthma (Hx+ and/or AR+) and 23% had a definitive diagnosis of asthma (AR+ with Hx+). Overall 47% of the population were atopic, atopy was proportionally higher in asthmatics (74%) than nonasthmatics (32%; p < 0.01). Analysis of the methacholine dose-response curves demonstrated that asthmatics were significantly (p < 0.01) more responsive than those with AR+ only, and nonasthmatics (AR-, Hx-) were more responsive than laboratory control subjects (p < 0.05), suggesting that these islanders may also carry an airway hyperresponsiveness gene. A frequency plot of the percent fall in FEV1 for all Hx- subjects compared with control data suggests a bimodal distribution consistent with a major gene mechanism for airway responsiveness. Genealogy mapping revealed that the islanders are direct descendants of the 15 original settlers, and historical records suggest at least two founders may have been asthmatic. The data confirm previous reports of a high asthma prevalence on Tristan and support the postulate that this prevalence is a result of gene enrichment occurring in isolated populations by virtue of extensive inbreeding and a probable founder effect.},
bibtype = {article},
author = {Zamel, N and McClean, P A and Sandell, P R and Siminovitch, K A and Slutsky, A S},
journal = {Am J Respir Crit Care Med},
number = {6 Pt 1}
}The genetical archaeology of the human genome. von Haeseler, A., Sajantila, A., & Paabo, S. Nat Genet, 14(2):135-140, 1996.
abstract bibtex
abstract bibtex
Palaentology and archaeology are disciplines that traditionally deal with the reconstruction of human origins and history. Recently, however, molecular genetics has come to make increasing contributions to this area. In particular, several data sets indicate that variation of the human gene pool originated in Africa within the last 200,000 years. Furthermore, the study of DNA sequences allows the detection of expansions in population size. Here we briefly summarize and exemplify how DNA sequences can be used to reconstruct the history of populations.
@article{
title = {The genetical archaeology of the human genome},
type = {article},
year = {1996},
identifiers = {[object Object]},
keywords = {*Gene Pool,*Genome, Human,DNA, Mitochondrial/genetics,Evolution, Molecular,Female,Human,Male,Models, Genetic,Phylogeny,Support, Non-U.S. Gov't,Variation (Genetics)/*genetics},
pages = {135-140},
volume = {14},
id = {da42c725-f648-32fa-a720-c48d07c5c47c},
created = {2017-06-19T13:46:05.495Z},
file_attached = {false},
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group_id = {b2078731-0913-33b9-8902-a53629a24e83},
last_modified = {2017-06-19T13:46:05.676Z},
tags = {03/09/17},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>Journal Article<m:linebreak/>Review<m:linebreak/>Review, Tutorial</m:note>},
abstract = {Palaentology and archaeology are disciplines that traditionally deal with the reconstruction of human origins and history. Recently, however, molecular genetics has come to make increasing contributions to this area. In particular, several data sets indicate that variation of the human gene pool originated in Africa within the last 200,000 years. Furthermore, the study of DNA sequences allows the detection of expansions in population size. Here we briefly summarize and exemplify how DNA sequences can be used to reconstruct the history of populations.},
bibtype = {article},
author = {von Haeseler, A and Sajantila, A and Paabo, S},
journal = {Nat Genet},
number = {2}
}Genetic epidemiology. Sham, P. Br Med Bull, 52(3):408-33., 1996.
abstract bibtex
abstract bibtex
Studies of families, twins, and adoptees have helped to quantify the genetic contributions to and overlaps between depression, anxiety, phobias and alcoholism, and to refine the boundaries of the schizophrenia spectrum. Analyses of covariance structures in twin data have confirmed genetic susceptibility and recent life stresses as the major determinants of depression. Genetic modelling of family data on schizophrenia and bipolar disorder indicates three or more common genes each having a small multiplicative effect on risk, although rare major genes may be present in some families. Linkage studies have localised genes for familial Alzheimer's disease on chromosomes 14 and 21; disease mutations on these chromosomes have since been isolated. Association studies have identified susceptibility (or protective) genes for Alzheimer's disease and alcoholism. Several tentative linkage and association findings in schizophrenia and bipolar disorder require further study.
@article{
title = {Genetic epidemiology},
type = {article},
year = {1996},
identifiers = {[object Object]},
keywords = {Alcoholism/psychology,Disease Susceptibility,Epidemiologic Methods,Human,Linkage (Genetics),Mental Disorders/*epidemiology/*genetics,Models, Genetic,Substance-Related Disorders/genetics,Support, Non-U.S. Gov't},
pages = {408-33.},
volume = {52},
id = {1651e57c-8e13-3a4c-a1cc-4e0fc67910bb},
created = {2017-06-19T13:42:36.715Z},
file_attached = {false},
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last_modified = {2017-06-19T13:42:36.823Z},
tags = {02/06/15},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article<m:linebreak/>Review<m:linebreak/>Review, Academic</m:note>},
abstract = {Studies of families, twins, and adoptees have helped to quantify the genetic contributions to and overlaps between depression, anxiety, phobias and alcoholism, and to refine the boundaries of the schizophrenia spectrum. Analyses of covariance structures in twin data have confirmed genetic susceptibility and recent life stresses as the major determinants of depression. Genetic modelling of family data on schizophrenia and bipolar disorder indicates three or more common genes each having a small multiplicative effect on risk, although rare major genes may be present in some families. Linkage studies have localised genes for familial Alzheimer's disease on chromosomes 14 and 21; disease mutations on these chromosomes have since been isolated. Association studies have identified susceptibility (or protective) genes for Alzheimer's disease and alcoholism. Several tentative linkage and association findings in schizophrenia and bipolar disorder require further study.},
bibtype = {article},
author = {Sham, P},
journal = {Br Med Bull},
number = {3}
}Genealogical information and the structure of rural Latin-American populations: reality and fantasy. Castilla, E., E. & Adams, J. Hum Hered, 46(5):241-55., 1996.
abstract bibtex
abstract bibtex
Genetic data organized in the form of genealogies can provide much information regarding the history and genetic structure of human populations. A large proportion of the population of Latin America is organized in small rural semi-isolated communities, with little immigration, and until the last 50-100 years, little emigration. These communities have a strong sense of their genealogical history, and this "genealogical conscience' is a frequent leitmotif in modern Latin-American literature. In this communication, we compare the characteristics of fictitious genealogies described in two masterpieces of Latin-American literature, Garcia Marquez' Cien Anos de Soledad (A Hundred Years of Solitude), and Verissimo's O Tempo e o Vento (Time and the Wind), with one existing well-studied population in Argentina, Aicuna. All three populations exhibit a number of common characteristics, such as histories of long periods of civil war, and large pedigrees with complex paths of inheritance resulting in complex patterns of inbreeding. Genetic themes common to all three are: (1) the use of genealogical records to substantiate the property of the land or the political power of a kinship; (2) the genealogical registry of biological descendants, independent of their legal or marital status in the clan; (3) the existence of pedigrees of the aristocratic branches in the same kindreds, which illustrate the legal principle of primogeniture; (4) the value of last names as indicators of kinships and the extent of genetic isolation, and (5) the awareness of the deleterious consequences of consanguinity.
@article{
title = {Genealogical information and the structure of rural Latin-American populations: reality and fantasy},
type = {article},
year = {1996},
identifiers = {[object Object]},
keywords = {*Genealogy and Heraldry,*Medicine in Literature,*Rural Population,Argentina,Brazil,Colombia,Consanguinity,Human,Latin America,Pedigree,Support, Non-U.S. Gov't},
pages = {241-55.},
volume = {46},
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created = {2017-06-19T13:42:10.981Z},
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notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {Genetic data organized in the form of genealogies can provide much information regarding the history and genetic structure of human populations. A large proportion of the population of Latin America is organized in small rural semi-isolated communities, with little immigration, and until the last 50-100 years, little emigration. These communities have a strong sense of their genealogical history, and this "genealogical conscience' is a frequent leitmotif in modern Latin-American literature. In this communication, we compare the characteristics of fictitious genealogies described in two masterpieces of Latin-American literature, Garcia Marquez' Cien Anos de Soledad (A Hundred Years of Solitude), and Verissimo's O Tempo e o Vento (Time and the Wind), with one existing well-studied population in Argentina, Aicuna. All three populations exhibit a number of common characteristics, such as histories of long periods of civil war, and large pedigrees with complex paths of inheritance resulting in complex patterns of inbreeding. Genetic themes common to all three are: (1) the use of genealogical records to substantiate the property of the land or the political power of a kinship; (2) the genealogical registry of biological descendants, independent of their legal or marital status in the clan; (3) the existence of pedigrees of the aristocratic branches in the same kindreds, which illustrate the legal principle of primogeniture; (4) the value of last names as indicators of kinships and the extent of genetic isolation, and (5) the awareness of the deleterious consequences of consanguinity.},
bibtype = {article},
author = {Castilla, E E and Adams, J},
journal = {Hum Hered},
number = {5}
}Speed of processing in the human visual system. Thorpe, S, Fize, D, & Marlot, C Nature, 381(6582):520–522, 1996. Place: ENGLAND ISBN: 0028-0836
doi abstract bibtex
doi abstract bibtex
How long does it take for the human visual system to process a complex natural image? Subjectively, recognition of familiar objects and scenes appears to be virtually instantaneous, but measuring this processing time experimentally has proved difficult. Behavioural measures such as reaction times can be used, but these include not only visual processing but also the time required for response execution. However, event-related potentials (ERPs) can sometimes reveal signs of neural processing well before the motor output. Here we use a go/no-go categorization task in which subjects have to decide whether a previously unseen photograph, flashed on for just 20 ms, contains an animal. ERP analysis revealed a frontal negativity specific to no-go trials that develops roughly 150 ms after stimulus onset. We conclude that the visual processing needed to perform this highly demanding task can be achieved in under 150 ms.
@article{thorpe_speed_1996,
title = {Speed of processing in the human visual system.},
volume = {381},
doi = {10.1038/381520a0},
abstract = {How long does it take for the human visual system to process a complex natural image? Subjectively, recognition of familiar objects and scenes appears to be virtually instantaneous, but measuring this processing time experimentally has proved difficult. Behavioural measures such as reaction times can be used, but these include not only visual processing but also the time required for response execution. However, event-related potentials (ERPs) can sometimes reveal signs of neural processing well before the motor output. Here we use a go/no-go categorization task in which subjects have to decide whether a previously unseen photograph, flashed on for just 20 ms, contains an animal. ERP analysis revealed a frontal negativity specific to no-go trials that develops roughly 150 ms after stimulus onset. We conclude that the visual processing needed to perform this highly demanding task can be achieved in under 150 ms.},
language = {eng},
number = {6582},
journal = {Nature},
author = {Thorpe, S and Fize, D and Marlot, C},
year = {1996},
pmid = {8632824},
note = {Place: ENGLAND
ISBN: 0028-0836},
keywords = {Adult, Evoked Potentials, Visual, Female, Humans, Male, Middle Aged, Reaction Time, Vision, Ocular, research support, non-u.s. gov't},
pages = {520--522},
}Frequencies of cystic fibrosis mutations in the Maine population: high proportion of unknown alleles in individuals of French-Canadian ancestry. Bayleran, J., K., Yan, H., Hopper, C., A., & Simpson, E., M. Hum Genet, 98(2):207-209, 1996.
Paper abstract bibtex
Paper abstract bibtex Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders in Caucasian populations. A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes this disorder. Reported here is the first analysis of CF mutations in the Maine population. We have screened 263 CF chromosomes for 16 previously reported mutations. Analysis of DNA from 124 apparently unrelated CF patients and 15 obligate carrier parents (whose partner and affected child were unavailable for study) resulted in the identification of 91% of the CF alleles and complete genotyping of 85% of the patients. The frequencies (%) of these mutations in the Maine population are delta F508 (75% of the chromosomes), G85E (0.76), R117H (0.76), I148T (1.1), 621 + 1G --> T (1.1), 711 + 1G --> T (3.0), A455E (1.1), 1717-1G --> A (1.1), G542X (1.9), G551D (1.9), R560T (0.76), Y1092X (0.38), W1282X (0.38), and N1303K (1.5). The exon 10 mutation, delta I507, and the exon 11 mutation, R553X, were not observed. Surprisingly, whereas only 5% of the alleles remain unidentified in the non-French population, the unidentified proportion in the French population is 19%. CF testing for the Maine population will be further improved as the as yet unidentified CF mutations in this population are characterized.
@article{
title = {Frequencies of cystic fibrosis mutations in the Maine population: high proportion of unknown alleles in individuals of French-Canadian ancestry},
type = {article},
year = {1996},
identifiers = {[object Object]},
keywords = {*Mutation,Alleles,Canada/ethnology,Cystic Fibrosis Transmembrane Conductance Regulato,Cystic Fibrosis/epidemiology/*genetics,Female,France/ethnology,Gene Frequency,Genotype,Human,Maine/epidemiology,Male,Support, Non-U.S. Gov't,Support, U.S. Gov't, Non-P.H.S.,Support, U.S. Gov't, P.H.S.},
pages = {207-209},
volume = {98},
id = {8cc8243a-e20d-3e84-beb1-dddbcca4a389},
created = {2017-06-19T13:44:32.001Z},
file_attached = {true},
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group_id = {b2078731-0913-33b9-8902-a53629a24e83},
last_modified = {2017-06-19T13:44:32.125Z},
tags = {04/09/01},
read = {false},
starred = {false},
authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>Journal Article</m:note>},
abstract = {Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders in Caucasian populations. A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes this disorder. Reported here is the first analysis of CF mutations in the Maine population. We have screened 263 CF chromosomes for 16 previously reported mutations. Analysis of DNA from 124 apparently unrelated CF patients and 15 obligate carrier parents (whose partner and affected child were unavailable for study) resulted in the identification of 91% of the CF alleles and complete genotyping of 85% of the patients. The frequencies (%) of these mutations in the Maine population are delta F508 (75% of the chromosomes), G85E (0.76), R117H (0.76), I148T (1.1), 621 + 1G --> T (1.1), 711 + 1G --> T (3.0), A455E (1.1), 1717-1G --> A (1.1), G542X (1.9), G551D (1.9), R560T (0.76), Y1092X (0.38), W1282X (0.38), and N1303K (1.5). The exon 10 mutation, delta I507, and the exon 11 mutation, R553X, were not observed. Surprisingly, whereas only 5% of the alleles remain unidentified in the non-French population, the unidentified proportion in the French population is 19%. CF testing for the Maine population will be further improved as the as yet unidentified CF mutations in this population are characterized.},
bibtype = {article},
author = {Bayleran, J K and Yan, H and Hopper, C A and Simpson, E M},
journal = {Hum Genet},
number = {2}
}Multineuronal codes in retinal signaling. Meister, M Proc Natl Acad Sci U S A, 93(2):609-14, 1996.
abstract bibtex
abstract bibtex
The visual world is presented to the brain through patterns of action potentials in the population of optic nerve fibers. Single-neuron recordings show that each retinal ganglion cell has a spatially restricted receptive field, a limited integration time, and a characteristic spectral sensitivity. Collectively, these response properties define the visual message conveyed by that neuron's action potentials. Since the size of the optic nerve is strictly constrained, one expects the retina to generate a highly efficient representation of the visual scene. By contrast, the receptive fields of nearby ganglion cells often overlap, suggesting great redundancy among the retinal output signals. Recent multineuron recordings may help resolve this paradox. They reveal concerted firing patterns among ganglion cells, in which small groups of nearby neurons fire synchronously with delays of only a few milliseconds. As there are many more such firing patterns than ganglion cells, such a distributed code might allow the retina to compress a large number of distinct visual messages into a small number of optic nerve fibers. This paper will review the evidence for a distributed coding scheme in the retinal output. The performance limits of such codes are analyzed with simple examples, illustrating that they allow a powerful trade-off between spatial and temporal resolution.
@Article{Meister1996,
author = {M Meister},
journal = {Proc Natl Acad Sci U S A},
title = {Multineuronal codes in retinal signaling.},
year = {1996},
number = {2},
pages = {609-14},
volume = {93},
abstract = {The visual world is presented to the brain through patterns of action
potentials in the population of optic nerve fibers. Single-neuron
recordings show that each retinal ganglion cell has a spatially restricted
receptive field, a limited integration time, and a characteristic
spectral sensitivity. Collectively, these response properties define
the visual message conveyed by that neuron's action potentials. Since
the size of the optic nerve is strictly constrained, one expects
the retina to generate a highly efficient representation of the visual
scene. By contrast, the receptive fields of nearby ganglion cells
often overlap, suggesting great redundancy among the retinal output
signals. Recent multineuron recordings may help resolve this paradox.
They reveal concerted firing patterns among ganglion cells, in which
small groups of nearby neurons fire synchronously with delays of
only a few milliseconds. As there are many more such firing patterns
than ganglion cells, such a distributed code might allow the retina
to compress a large number of distinct visual messages into a small
number of optic nerve fibers. This paper will review the evidence
for a distributed coding scheme in the retinal output. The performance
limits of such codes are analyzed with simple examples, illustrating
that they allow a powerful trade-off between spatial and temporal
resolution.},
keywords = {Action Potentials, Models, Neurological, Nerve Net, Optic Nerve, Retinal Ganglion Cells, Signal Transduction, Support, Non-U.S. Gov't, U.S. Gov't, Non-P.H.S., P.H.S., Visual Perception, 8570603},
}A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada). De Braekeleer, M., Perusse, L., Cantin, L., Bouchard, J., M., & Mathieu, J. Ann Hum Genet, 60(Pt 2):99-104., 1996.
abstract bibtex
abstract bibtex
The genealogies of 533 individuals with an intracranial aneurysm (IA) born in the Saguenay-Lac-Saint-Jean region, a geographically isolated area located in northeastern Quebec, were reconstructed using a population-based register. A control group consisting of three individuals of the same sex and born on the same day and in the same municipality than the IA patients was created; the genealogies of the 1599 controls were also reconstructed. The coefficients of inbreeding and kinship were calculated. Familial aggregation, i.e. the presence of IA in two or more first- to third-degree relatives, was also sought. The mean inbreeding coefficient was lower in the IA group than in the control group (7.92 x 10(-4) versus 10.04 x 10(-4)). The mean kinship coefficient was higher in the IA group than in the control group (2.17 x 10(-4) versus 1.55 x 10(-4)). Forty-eight IA patients (9.0%) were first-degree relatives compared to only 1.9% of the control individuals. The proportion of individuals showing familial aggregation was higher in the IA group than in the control group (29.8% and 18.6% respectively). These results strongly suggest that some IA are genetically determined in this population.
@article{
title = {A study of inbreeding and kinship in intracranial aneurysms in the Saguenay Lac-Saint-Jean region (Quebec, Canada)},
type = {article},
year = {1996},
identifiers = {[object Object]},
keywords = {*Consanguinity,*Family,Female,Human,Intracranial Aneurysm/*genetics,Male,Quebec,Support, Non-U.S. Gov't},
pages = {99-104.},
volume = {60},
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source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {The genealogies of 533 individuals with an intracranial aneurysm (IA) born in the Saguenay-Lac-Saint-Jean region, a geographically isolated area located in northeastern Quebec, were reconstructed using a population-based register. A control group consisting of three individuals of the same sex and born on the same day and in the same municipality than the IA patients was created; the genealogies of the 1599 controls were also reconstructed. The coefficients of inbreeding and kinship were calculated. Familial aggregation, i.e. the presence of IA in two or more first- to third-degree relatives, was also sought. The mean inbreeding coefficient was lower in the IA group than in the control group (7.92 x 10(-4) versus 10.04 x 10(-4)). The mean kinship coefficient was higher in the IA group than in the control group (2.17 x 10(-4) versus 1.55 x 10(-4)). Forty-eight IA patients (9.0%) were first-degree relatives compared to only 1.9% of the control individuals. The proportion of individuals showing familial aggregation was higher in the IA group than in the control group (29.8% and 18.6% respectively). These results strongly suggest that some IA are genetically determined in this population.},
bibtype = {article},
author = {De Braekeleer, M and Perusse, L and Cantin, L and Bouchard, J M and Mathieu, J},
journal = {Ann Hum Genet},
number = {Pt 2}
}1995 (2)
Variability of the genetic contribution of Quebec population founders associated to some deleterious genes. Heyer, E. & Tremblay, M. Am J Hum Genet, 56(4):970-8., 1995.
Paper abstract bibtex
Paper abstract bibtex Relatively high frequencies of some rare inherited disorders can be found in the Saguenay Region (Quebec). To understand this phenomenon, a research project on the 17th-century founder effect that led to the formation of French Canadians' gene pool is being carried out. The focus of this study is on founders who contributed to the Saguenay gene pool and who are related to contemporary probands suffering from any one of five hereditary diseases: cystic fibrosis, tyrosinemia, hemochromatosis, Charlevoix-Saguenay spastic ataxia, and sensorimotor polyneuropathia with or without agenesis of the corpus callosum. A control group has been added for comparison purposes. Altogether, 545 ascending genealogies have been reconstructed, using the Interuniversity Institute for Population Research's RETRO database, leading to > 2,500 founders. The genetic contribution of each founder to each group has been measured. Results show that (1) nearly 80% of the individuals' gene pool come from founders who settled in Nouvelle-France in the 17th century, whatever the group; (2) 15% of the founders explain 90% of the total genetic contribution of the founders, but this pattern varies from one group to another; (3) there is no subgroup of founders more related to any given group of individuals.
@article{
title = {Variability of the genetic contribution of Quebec population founders associated to some deleterious genes},
type = {article},
year = {1995},
identifiers = {[object Object]},
keywords = {*Variation (Genetics),Genes/*genetics,Genetic Diseases,Human,Inborn/*genetics,Non-U.S. Gov't,Quebec,Support},
pages = {970-8.},
volume = {56},
id = {aca70703-612e-37dc-ad8a-67357d5d675c},
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file_attached = {true},
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tags = {03/06/15},
read = {false},
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authored = {false},
confirmed = {true},
hidden = {false},
source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {Relatively high frequencies of some rare inherited disorders can be found in the Saguenay Region (Quebec). To understand this phenomenon, a research project on the 17th-century founder effect that led to the formation of French Canadians' gene pool is being carried out. The focus of this study is on founders who contributed to the Saguenay gene pool and who are related to contemporary probands suffering from any one of five hereditary diseases: cystic fibrosis, tyrosinemia, hemochromatosis, Charlevoix-Saguenay spastic ataxia, and sensorimotor polyneuropathia with or without agenesis of the corpus callosum. A control group has been added for comparison purposes. Altogether, 545 ascending genealogies have been reconstructed, using the Interuniversity Institute for Population Research's RETRO database, leading to > 2,500 founders. The genetic contribution of each founder to each group has been measured. Results show that (1) nearly 80% of the individuals' gene pool come from founders who settled in Nouvelle-France in the 17th century, whatever the group; (2) 15% of the founders explain 90% of the total genetic contribution of the founders, but this pattern varies from one group to another; (3) there is no subgroup of founders more related to any given group of individuals.},
bibtype = {article},
author = {Heyer, E and Tremblay, M},
journal = {Am J Hum Genet},
number = {4}
}Origins and affinities of modern humans: a comparison of mitochondrial and nuclear genetic data. Jorde, L., B., Bamshad, M., J., Watkins, W., S., Zenger, R., Fraley, A., E., Krakowiak, P., A., Carpenter, K., D., Soodyall, H., Jenkins, T., & Rogers, A., R. Am J Hum Genet, 57(3):523-38., 1995.
abstract bibtex
abstract bibtex
To test hypotheses about the origin of modern humans, we analyzed mtDNA sequences, 30 nuclear restriction-site polymorphisms (RSPs), and 30 tetranucleotide short tandem repeat (STR) polymorphisms in 243 Africans, Asians, and Europeans. An evolutionary tree based on mtDNA displays deep African branches, indicating greater genetic diversity for African populations. This finding, which is consistent with previous mtDNA analyses, has been interpreted as evidence for an African origin of modern humans. Both sets of nuclear polymorphisms, as well as a third set of trinucleotide polymorphisms, are highly consistent with one another but fail to show deep branches for African populations. These results, which represent the first direct comparison of mtDNA and nuclear genetic data in major continental populations, undermine the genetic evidence for an African origin of modern humans.
@article{
title = {Origins and affinities of modern humans: a comparison of mitochondrial and nuclear genetic data},
type = {article},
year = {1995},
identifiers = {[object Object]},
keywords = {*Evolution,*Genetics, Population,*Polymorphism (Genetics),Africa,Asia,Base Sequence,DNA, Mitochondrial/*genetics,Europe,Human,Molecular Sequence Data,Support, Non-U.S. Gov't,Support, U.S. Gov't, Non-P.H.S.,Support, U.S. Gov't, P.H.S.,Variation (Genetics)},
pages = {523-38.},
volume = {57},
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abstract = {To test hypotheses about the origin of modern humans, we analyzed mtDNA sequences, 30 nuclear restriction-site polymorphisms (RSPs), and 30 tetranucleotide short tandem repeat (STR) polymorphisms in 243 Africans, Asians, and Europeans. An evolutionary tree based on mtDNA displays deep African branches, indicating greater genetic diversity for African populations. This finding, which is consistent with previous mtDNA analyses, has been interpreted as evidence for an African origin of modern humans. Both sets of nuclear polymorphisms, as well as a third set of trinucleotide polymorphisms, are highly consistent with one another but fail to show deep branches for African populations. These results, which represent the first direct comparison of mtDNA and nuclear genetic data in major continental populations, undermine the genetic evidence for an African origin of modern humans.},
bibtype = {article},
author = {Jorde, L B and Bamshad, M J and Watkins, W S and Zenger, R and Fraley, A E and Krakowiak, P A and Carpenter, K D and Soodyall, H and Jenkins, T and Rogers, A R},
journal = {Am J Hum Genet},
number = {3}
}1992 (2)
X-linked nephrogenic diabetes insipidus: from the ship Hopewell to RFLP studies. Bichet, D., G., Hendy, G., N., Lonergan, M., Arthus, M., F., Ligier, S., Pausova, Z., Kluge, R., Zingg, H., Saenger, P., Oppenheimer, E., & et al. Am J Hum Genet, 51(5):1089-1102., 1992.
abstract bibtex
abstract bibtex
Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V2 vasopressin receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and NDI has been reported. In 1969, Bode and Crawford proposed, under the term "the Hopewell hypothesis," that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell early settlers, either by haplotype or by genealogical analysis. We confirm the locus homogeneity of the disease by linkage analysis in ethnically diverse families. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration.
@article{
title = {X-linked nephrogenic diabetes insipidus: from the ship Hopewell to RFLP studies},
type = {article},
year = {1992},
identifiers = {[object Object]},
keywords = {*Polymorphism, Restriction Fragment Length,*X Chromosome,Blotting, Southern,Diabetes Insipidus/epidemiology/*genetics,Female,Genetic Markers/genetics,Haplotypes,Heterozygote Detection,Human,Lod Score,Male,Nova Scotia/epidemiology,Pedigree,Polymerase Chain Reaction,Prenatal Diagnosis,Prevalence,Support, Non-U.S. Gov't},
pages = {1089-1102.},
volume = {51},
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abstract = {Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V2 vasopressin receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and NDI has been reported. In 1969, Bode and Crawford proposed, under the term "the Hopewell hypothesis," that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell early settlers, either by haplotype or by genealogical analysis. We confirm the locus homogeneity of the disease by linkage analysis in ethnically diverse families. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration.},
bibtype = {article},
author = {Bichet, D G and Hendy, G N and Lonergan, M and Arthus, M F and Ligier, S and Pausova, Z and Kluge, R and Zingg, H and Saenger, P and Oppenheimer, E and et al., undefined},
journal = {Am J Hum Genet},
number = {5}
}Calculation of genetic identity coefficients. Lange, K. & Sinsheimer, J., S. Ann Hum Genet, 56(Pt 4):339-46., 1992.
abstract bibtex
abstract bibtex
Genetic identity coefficients define the kind and amount of gene sharing between two relatives at a single locus. Non-recursive computation of these probabilities depends on cumbersome graph-tracing algorithms. Closely related to the identity coefficients are certain generalized kinship coefficients which can be computed recursively. The present paper clarifies some ideas of Karigl about how to relate identity coefficients to generalized kinship coefficients.
@article{
title = {Calculation of genetic identity coefficients},
type = {article},
year = {1992},
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pages = {339-46.},
volume = {56},
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abstract = {Genetic identity coefficients define the kind and amount of gene sharing between two relatives at a single locus. Non-recursive computation of these probabilities depends on cumbersome graph-tracing algorithms. Closely related to the identity coefficients are certain generalized kinship coefficients which can be computed recursively. The present paper clarifies some ideas of Karigl about how to relate identity coefficients to generalized kinship coefficients.},
bibtype = {article},
author = {Lange, K and Sinsheimer, J S},
journal = {Ann Hum Genet},
number = {Pt 4}
}1990 (2)
Spectral properties of V4 neurons in the macaque. Schein, S J & Desimone, R J Neurosci, 10(10):3369–3389, 1990. Place: UNITED STATES ISBN: 0270-6474
abstract bibtex
abstract bibtex
Spectral properties of 129 cells in the V4 area of 5 macaque monkeys were studied quantitatively with narrow-band and broad-band colored lights. The large majority of cells exhibited some degree of wavelength sensitivity within their receptive fields. The half-bandwidth of the primary peak in the spectral-response curve was less than 50 nm for 72% of the cells; the mean half-bandwidth of these cells, 27 nm, is similar to that found for color-opponent ganglion cells and cells in the parvocellular dorsal lateral geniculate nucleus (dLGN). Contrast-response functions indicated that the narrow spectral tuning of these cells derived from cone opponent interactions. From comparison of receptive-field sizes, we suggest that a typical V4 neuron sums inputs that ultimately derive from several thousand ganglion or parvocellular dLGN cells. In spite of their wavelength sensitivity, most V4 cells had properties that would not fit some simple criteria for classification as "color selective." First, few cells showed overt signs of color opponency, namely, on-inhibition or off-excitation to spectrally opponent wavelengths. Second, about 30% of the cells in V4 had spectral-response curves with 2 peaks. (The wavelength distribution of these second peaks was almost identical to that of primary peaks, and combinations of peak wavelengths were fairly random.) Third, most cells responded to white light; overall, the response to white light was about 60% of that to the best narrow-band or broad-band colored light. Similarly, most V4 cells gave at least a small response to all or nearly all of the different broad-band colored lights we presented. Therefore, a given V4 cell is very likely to respond to most of the colored or white surfaces in natural scenes. These combinations of response properties probably explain the widely divergent percentages of "color" cells reported in previous studies of V4. The most unusual spectral property we found in V4 was a large, spectrally sensitive surround outside the "classical receptive field" of most cells. Although stimulation of the surround by itself did not cause any response, surround stimulation could completely suppress the response to even the optimally colored stimulus in the receptive field. In general, the optimal wavelengths for receptive-field excitation and surround suppression were the same or nearly so. Thus, "color contrast" may be computed in V4. In some cases, contrasting wavelengths in the surround caused moderate enhancement of response to a receptive-field stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)
@article{schein_spectral_1990,
title = {Spectral properties of {V4} neurons in the macaque.},
volume = {10},
abstract = {Spectral properties of 129 cells in the V4 area of 5 macaque monkeys were studied quantitatively with narrow-band and broad-band colored lights. The large majority of cells exhibited some degree of wavelength sensitivity within their receptive fields. The half-bandwidth of the primary peak in the spectral-response curve was less than 50 nm for 72\% of the cells; the mean half-bandwidth of these cells, 27 nm, is similar to that found for color-opponent ganglion cells and cells in the parvocellular dorsal lateral geniculate nucleus (dLGN). Contrast-response functions indicated that the narrow spectral tuning of these cells derived from cone opponent interactions. From comparison of receptive-field sizes, we suggest that a typical V4 neuron sums inputs that ultimately derive from several thousand ganglion or parvocellular dLGN cells. In spite of their wavelength sensitivity, most V4 cells had properties that would not fit some simple criteria for classification as "color selective." First, few cells showed overt signs of color opponency, namely, on-inhibition or off-excitation to spectrally opponent wavelengths. Second, about 30\% of the cells in V4 had spectral-response curves with 2 peaks. (The wavelength distribution of these second peaks was almost identical to that of primary peaks, and combinations of peak wavelengths were fairly random.) Third, most cells responded to white light; overall, the response to white light was about 60\% of that to the best narrow-band or broad-band colored light. Similarly, most V4 cells gave at least a small response to all or nearly all of the different broad-band colored lights we presented. Therefore, a given V4 cell is very likely to respond to most of the colored or white surfaces in natural scenes. These combinations of response properties probably explain the widely divergent percentages of "color" cells reported in previous studies of V4. The most unusual spectral property we found in V4 was a large, spectrally sensitive surround outside the "classical receptive field" of most cells. Although stimulation of the surround by itself did not cause any response, surround stimulation could completely suppress the response to even the optimally colored stimulus in the receptive field. In general, the optimal wavelengths for receptive-field excitation and surround suppression were the same or nearly so. Thus, "color contrast" may be computed in V4. In some cases, contrasting wavelengths in the surround caused moderate enhancement of response to a receptive-field stimulus.(ABSTRACT TRUNCATED AT 400 WORDS)},
language = {eng},
number = {10},
journal = {J Neurosci},
author = {Schein, S J and Desimone, R},
year = {1990},
pmid = {2213146},
note = {Place: UNITED STATES
ISBN: 0270-6474},
keywords = {Animals, Cerebral Cortex, Color Perception, Macaca fascicularis, Neurons, Photic Stimulation, Spectrophotometry, Visual Cortex, research support, non-u.s. gov't, research support, u.s. gov't, p.h.s.},
pages = {3369--3389},
}Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada). Mathieu, J., De Braekeleer, M., & Prevost, C. Neurology, 40(5):839-42., 1990.
abstract bibtex
abstract bibtex
The prevalence of myotonic dystrophy (MyD) in the Saguenay-Lac-Saint-Jean (SLSJ) region (Quebec, Canada) is 30 to 60 times the world's prevalence. We identified 746 patients (673 still alive) distributed in 88 families. Using a population-based register of the SLSJ area and several marriage repositories from northeastern Quebec, we could trace back all patients to a couple who settled in "Nouvelle-France" in 1657. The MyD gene was then passed on over 10 to 14 generations. This genealogical reconstruction is a strong argument in favor of the genetic homogeneity of MyD in the SLSJ region.
@article{
title = {Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada)},
type = {article},
year = {1990},
identifiers = {[object Object]},
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pages = {839-42.},
volume = {40},
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abstract = {The prevalence of myotonic dystrophy (MyD) in the Saguenay-Lac-Saint-Jean (SLSJ) region (Quebec, Canada) is 30 to 60 times the world's prevalence. We identified 746 patients (673 still alive) distributed in 88 families. Using a population-based register of the SLSJ area and several marriage repositories from northeastern Quebec, we could trace back all patients to a couple who settled in "Nouvelle-France" in 1657. The MyD gene was then passed on over 10 to 14 generations. This genealogical reconstruction is a strong argument in favor of the genetic homogeneity of MyD in the SLSJ region.},
bibtype = {article},
author = {Mathieu, J and De Braekeleer, M and Prevost, C},
journal = {Neurology},
number = {5}
}1989 (3)
Origin and diffusion of the myotonic dystrophy gene in the Saguenay region (Quebec). Bouchard, G., Roy, R., Declos, M., Mathieu, J., & Kouladjian, K. Can J Neurol Sci, 16(1):119-122, 1989.
Website abstract bibtex
Website abstract bibtex A very high prevalence (approximately 1/475 in 1985) of myotonic dystrophy (Steinert disease) is observed in the Saguenay region, which is located in the north-east part of the Province of Quebec. For various reasons, however, the literature on the subject generally associates a high degree of selective disadvantage with this gene, which seems to contradict the Saguenay data. Using a computerized regional population register, we have reconstituted patients' genealogies and family biographies. We have thus been able to study the origin of the gene and to compare the demographic behavior of patients and controls. On the whole, patients seem to be very little disadvantaged compared to controls, in terms of reproduction as well as of geographical and occupational mobility.
@article{
title = {Origin and diffusion of the myotonic dystrophy gene in the Saguenay region (Quebec)},
type = {article},
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abstract = {A very high prevalence (approximately 1/475 in 1985) of myotonic dystrophy (Steinert disease) is observed in the Saguenay region, which is located in the north-east part of the Province of Quebec. For various reasons, however, the literature on the subject generally associates a high degree of selective disadvantage with this gene, which seems to contradict the Saguenay data. Using a computerized regional population register, we have reconstituted patients' genealogies and family biographies. We have thus been able to study the origin of the gene and to compare the demographic behavior of patients and controls. On the whole, patients seem to be very little disadvantaged compared to controls, in terms of reproduction as well as of geographical and occupational mobility.},
bibtype = {article},
author = {Bouchard, Gérard and Roy, R and Declos, M and Mathieu, J and Kouladjian, K},
journal = {Can J Neurol Sci},
number = {1}
}Contribution of linear spatiotemporal receptive field structure to velocity selectivity of simple cells in area 17 of cat. McLean, J & Palmer, L. Vision Res, 29(6):675-9, 1989.
abstract bibtex
abstract bibtex
We have examined the spatiotemporal structure of simple receptive fields in the cat's striate cortex by cross-correlating their spike trains with an ensemble of stimuli consisting of stationary bright and dark spots whose position was randomized on each 50 msec frame. Receptive fields were found to be either separable or inseparable in space-time and responses to moving stimuli were predicted from the spatiotemporal structure of the cell under study. Most simple cells with separable spatiotemporal receptive fields were not direction selective. All simple cells with inseparable spatiotemporal receptive fields were found to prefer movement in one direction. The optimal speed and direction were estimable from the slope of individual subregions observed in the space-time plane. The results are consistent with a linear model for direction selectivity.
@Article{McLean1989,
author = {J McLean and LA Palmer},
journal = {Vision Res},
title = {Contribution of linear spatiotemporal receptive field structure to velocity selectivity of simple cells in area 17 of cat.},
year = {1989},
number = {6},
pages = {675-9},
volume = {29},
abstract = {We have examined the spatiotemporal structure of simple receptive
fields in the cat's striate cortex by cross-correlating their spike
trains with an ensemble of stimuli consisting of stationary bright
and dark spots whose position was randomized on each 50 msec frame.
Receptive fields were found to be either separable or inseparable
in space-time and responses to moving stimuli were predicted from
the spatiotemporal structure of the cell under study. Most simple
cells with separable spatiotemporal receptive fields were not direction
selective. All simple cells with inseparable spatiotemporal receptive
fields were found to prefer movement in one direction. The optimal
speed and direction were estimable from the slope of individual subregions
observed in the space-time plane. The results are consistent with
a linear model for direction selectivity.},
keywords = {Computing Methodologies, Human, Language, Learning, Mental Processes, Models, Theoretical, Stochastic Processes, Support, U.S. Gov't, Non-P.H.S., Cognition, Linguistics, Neural Networks (Computer), Practice (Psychology), Non-U.S. Gov't, Memory, Psychological, Task Performance and Analysis, Time Factors, Visual Perception, Adult, Attention, Discrimination Learning, Female, Male, Short-Term, Mental Recall, Orientation, Pattern Recognition, Visual, Perceptual Masking, Reading, Concept Formation, Form Perception, Animals, Corpus Striatum, Shrews, P.H.S., Visual Cortex, Visual Pathways, Acoustic Stimulation, Auditory Cortex, Auditory Perception, Cochlea, Ear, Gerbillinae, Glycine, Hearing, Neurons, Space Perception, Strychnine, Adolescent, Decision Making, Reaction Time, Astrocytoma, Brain Mapping, Brain Neoplasms, Cerebral Cortex, Electric Stimulation, Electrophysiology, Epilepsy, Temporal Lobe, Evoked Potentials, Frontal Lobe, Noise, Parietal Lobe, Scalp, Child, Language Development, Psycholinguistics, Brain, Perception, Speech, Vocalization, Animal, Discrimination (Psychology), Hippocampus, Rats, Calcium, Chelating Agents, Excitatory Postsynaptic Potentials, Glutamic Acid, Guanosine Diphosphate, In Vitro, Neuronal Plasticity, Pyramidal Cells, Receptors, AMPA, Metabotropic Glutamate, N-Methyl-D-Aspartate, Somatosensory Cortex, Synapses, Synaptic Transmission, Thionucleotides, Action Potentials, Calcium Channels, L-Type, Electric Conductivity, Entorhinal Cortex, Neurological, Long-Evans, Infant, Mathematics, Statistics, Probability Learning, Problem Solving, Psychophysics, Association Learning, Child Psychology, Habituation (Psychophysiology), Probability Theory, Analysis of Variance, Semantics, Symbolism, Behavior, Eye Movements, Macaca mulatta, Prefrontal Cortex, Cats, Dogs, Haplorhini, Photic Stimulation, Electroencephalography, Nervous System Physiology, Darkness, Grasshoppers, Light, Membrane Potentials, Neural Inhibition, Afferent, Picrotoxin, Vision, Deoxyglucose, Injections, Microspheres, Neural Pathways, Rhodamines, Choice Behavior, Speech Perception, Verbal Learning, Dominance, Cerebral, Fixation, Ocular, Language Tests, Random Allocation, Comparative Study, Saguinus, Sound Spectrography, Species Specificity, Audiometry, Auditory Threshold, Calibration, Data Interpretation, Statistical, Anesthesia, General, Electrodes, Implanted, Pitch Perception, Sound Localization, Paired-Associate Learning, Serial Learning, Auditory, Age Factors, Motion Perception, Brain Injuries, Computer Simulation, Blindness, Psychomotor Performance, Color Perception, Signal Detection (Psychology), Judgment, ROC Curve, Regression Analysis, Music, Probability, Arm, Cerebrovascular Disorders, Hemiplegia, Movement, Muscle, Skeletal, Myoclonus, Robotics, Magnetoencephalography, Phonetics, Software, Speech Production Measurement, Epilepsies, Partial, Laterality, Stereotaxic Techniques, Germany, Speech Acoustics, Verbal Behavior, Child Development, Instinct, Brain Stem, Coma, Diagnosis, Differential, Hearing Disorders, Hearing Loss, Central, Neuroma, Acoustic, Dendrites, Down-Regulation, Patch-Clamp Techniques, Wistar, Up-Regulation, Aged, Aphasia, Middle Aged, Cones (Retina), Primates, Retina, Retinal Ganglion Cells, 2626824},
}Genetic structure of the human population in the Po delta. Beretta, M., Mazzetti, P., Mamolini, E., Gavina, R., Barale, R., Vullo, C., Ravani, A., Franze, A., Sapigni, T., Soracco, E., & et al. Am J Hum Genet, 45(1):49-62., 1989.
abstract bibtex
abstract bibtex
The genetic structure of the population of Ferrara Province in the Po delta in Italy was investigated using chi 2 analysis, kinship analysis, analysis of correspondences, and geographical mapping of principal components of gene frequencies. chi 2 Analysis tests for Hardy-Weinberg equilibrium and for heterogeneity of gene and phenotype frequencies; kinship analysis tests for association between indicators of genetic and geographic proximity; analysis of correspondences relates localities and genetic systems in an eigenvectorial space; and geographic mapping displays the principal components of gene frequencies in the real space. In 1,364 adults in 26 residential units, seven presumably neutral isoenzyme systems were typed; ACP1 ESD, GLO I, GPT, PGD, PGM1 and PGP. It was found that average kinship for these neutral systems is correlated with geographic distance in this small area, but not as strongly as kinship for beta-thalassemia. A north-south gradient was observed for ESD. Analysis of correspondences indicated GPT, PGM1, and GLO I as the systems contributing most to differentiation within the province. The maps obtained from principal components of gene frequencies were consistent with the migrational history of the area.
@article{
title = {Genetic structure of the human population in the Po delta},
type = {article},
year = {1989},
identifiers = {[object Object]},
keywords = {*Genetics, Medical,Adult,Alleles,Demography,Gene Frequency,Heterozygote Detection,Human,Isoenzymes/blood/*genetics,Italy,Phenotype,Support, Non-U.S. Gov't},
pages = {49-62.},
volume = {45},
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abstract = {The genetic structure of the population of Ferrara Province in the Po delta in Italy was investigated using chi 2 analysis, kinship analysis, analysis of correspondences, and geographical mapping of principal components of gene frequencies. chi 2 Analysis tests for Hardy-Weinberg equilibrium and for heterogeneity of gene and phenotype frequencies; kinship analysis tests for association between indicators of genetic and geographic proximity; analysis of correspondences relates localities and genetic systems in an eigenvectorial space; and geographic mapping displays the principal components of gene frequencies in the real space. In 1,364 adults in 26 residential units, seven presumably neutral isoenzyme systems were typed; ACP1 ESD, GLO I, GPT, PGD, PGM1 and PGP. It was found that average kinship for these neutral systems is correlated with geographic distance in this small area, but not as strongly as kinship for beta-thalassemia. A north-south gradient was observed for ESD. Analysis of correspondences indicated GPT, PGM1, and GLO I as the systems contributing most to differentiation within the province. The maps obtained from principal components of gene frequencies were consistent with the migrational history of the area.},
bibtype = {article},
author = {Beretta, M and Mazzetti, P and Mamolini, E and Gavina, R and Barale, R and Vullo, C and Ravani, A and Franze, A and Sapigni, T and Soracco, E and et al., undefined},
journal = {Am J Hum Genet},
number = {1}
}1987 (1)
Inbreeding and prereproductive mortality in the Old Order Amish. II. Genealogic epidemiology of prereproductive mortality. Khoury, M., J., Cohen, B., H., Newill, C., A., Bias, W., & McKusick, V., A. Am J Epidemiol, 125(3):462-72., 1987.
abstract bibtex
abstract bibtex
The effects of offspring and parental inbreeding on prereproductive mortality (death before age 20 years) in the historical population of the Lancaster County, Pennsylvania, Old Order Amish were investigated using the Amish genealogic registry, which contains information on 42,465 births dating to the time of the pioneer migrants in the 1700s. Inbreeding coefficients for offspring and parents were computed using the path method of tracing common ancestors in the multigenerational pedigrees. In this population, prereproductive mortality declined from about 15% in the late 1800s to about 5% after 1930. Offspring inbreeding was found to be an independent predictor of prereproductive mortality after multivariate adjustment for demographic risk factors for mortality. Moreover, the higher the coefficient, the higher the relative risk of prereproductive death, and the higher the risk of multiple deaths in the same sibship. There was no evidence of declining inbreeding effects over 10 generations of continuous inbreeding, nor of any significant parental inbreeding effects. Because of the high levels of inbreeding, it could be shown that inbreeding accounts for about 40% of all prereproductive deaths in the present population. Genetic load analysis showed an average of about 1.7 lethal equivalents and a mostly mutational load.
@article{
title = {Inbreeding and prereproductive mortality in the Old Order Amish. II. Genealogic epidemiology of prereproductive mortality},
type = {article},
year = {1987},
identifiers = {[object Object]},
keywords = {*Consanguinity,*Marriage,*Mortality,*Religion,Adult,Epidemiologic Methods,Female,Human,Male,Middle Age,Parents,Pennsylvania,Risk,Support, Non-U.S. Gov't,Time Factors},
pages = {462-72.},
volume = {125},
id = {6006ab20-a6aa-3b78-8ded-85354e6c3a0c},
created = {2017-06-19T13:43:48.964Z},
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last_modified = {2017-06-19T13:43:49.091Z},
tags = {02/02/04},
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source_type = {Journal Article},
notes = {<m:note>eng<m:linebreak/>Journal Article</m:note>},
abstract = {The effects of offspring and parental inbreeding on prereproductive mortality (death before age 20 years) in the historical population of the Lancaster County, Pennsylvania, Old Order Amish were investigated using the Amish genealogic registry, which contains information on 42,465 births dating to the time of the pioneer migrants in the 1700s. Inbreeding coefficients for offspring and parents were computed using the path method of tracing common ancestors in the multigenerational pedigrees. In this population, prereproductive mortality declined from about 15% in the late 1800s to about 5% after 1930. Offspring inbreeding was found to be an independent predictor of prereproductive mortality after multivariate adjustment for demographic risk factors for mortality. Moreover, the higher the coefficient, the higher the relative risk of prereproductive death, and the higher the risk of multiple deaths in the same sibship. There was no evidence of declining inbreeding effects over 10 generations of continuous inbreeding, nor of any significant parental inbreeding effects. Because of the high levels of inbreeding, it could be shown that inbreeding accounts for about 40% of all prereproductive deaths in the present population. Genetic load analysis showed an average of about 1.7 lethal equivalents and a mostly mutational load.},
bibtype = {article},
author = {Khoury, M J and Cohen, B H and Newill, C A and Bias, W and McKusick, V A},
journal = {Am J Epidemiol},
number = {3}
}