Identification of amygdala-expressed genes associated with autism spectrum disorder. Herrero, M. J., Velmeshev, D., Hernandez-Pineda, D., Sethi, S., Sorrells, S., Banerjee, P., Sullivan, C., Gupta, A. R, Kriegstein, A. R, & Corbin, J. G Mol Autism, 11(1):39, May, 2020. abstract bibtex BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development. METHODS: Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD. RESULTS: Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline. LIMITATIONS: We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages. CONCLUSIONS: Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.
@ARTICLE{Herrero2020-vo,
title = "Identification of amygdala-expressed genes associated with autism
spectrum disorder",
author = "Herrero, Maria Jesus and Velmeshev, Dmitry and Hernandez-Pineda,
David and Sethi, Saarthak and Sorrells, Shawn and Banerjee, Payal
and Sullivan, Catherine and Gupta, Abha R and Kriegstein, Arnold
R and Corbin, Joshua G",
abstract = "BACKGROUND: Studies of individuals with autism spectrum disorder
(ASD) have revealed a strong multigenic basis with the
identification of hundreds of ASD susceptibility genes. ASD is
characterized by social deficits and a range of other phenotypes,
implicating complex genetics and involvement of a variety of
brain regions. However, how mutations and mis-expression of
select gene sets are associated with the behavioral components of
ASD remains unknown. We reasoned that for genes to be associated
with ASD core behaviors they must be: (1) expressed in brain
regions relevant to ASD social behaviors and (2) expressed during
the ASD susceptible window of brain development. METHODS:
Focusing on the amygdala, a brain region whose dysfunction has
been highly implicated in the social component of ASD, we mined
publicly available gene expression databases to identify
ASD-susceptibility genes expressed during human and mouse
amygdala development. We found that a large cohort of known ASD
susceptibility genes is expressed in the developing human and
mouse amygdala. We further performed analysis of single-nucleus
RNA-seq (snRNA-seq) data from microdissected amygdala tissue from
five ASD and five control human postmortem brains ranging in age
from 4 to 20 years to elucidate cell type specificity of
amygdala-expressed genes and their dysregulation in ASD. RESULTS:
Our analyses revealed that of the high-ranking ASD susceptibility
genes, 80 are expressed in both human and mouse amygdala during
fetal to early postnatal stages of development. Our human
snRNA-seq analyses revealed cohorts of genes with altered
expression in the ASD amygdala postnatally, especially within
excitatory neurons, with dysregulated expression of seven genes
predicted from our datamining pipeline. LIMITATIONS: We were
limited by the ages for which we were able to obtain human
tissue; therefore, the results from our datamining pipeline
approach will require validation, to the extent possible, in
human tissue from earlier developmental stages. CONCLUSIONS: Our
pipeline narrows down the number of amygdala-expressed genes
possibly involved in the social pathophysiology of ASD. Our human
single-nucleus gene expression analyses revealed that ASD is
characterized by changes in gene expression in specific cell
types in the early postnatal amygdala.",
journal = "Mol Autism",
volume = 11,
number = 1,
pages = "39",
month = may,
year = 2020,
keywords = "ASD genes; Amygdala; Autism spectrum disorder; Brain development;
Single nucleus RNA sequencing",
language = "en"
}
Downloads: 0
{"_id":"8x2uJ5FRBFFa88DN3","bibbaseid":"herrero-velmeshev-hernandezpineda-sethi-sorrells-banerjee-sullivan-gupta-etal-identificationofamygdalaexpressedgenesassociatedwithautismspectrumdisorder-2020","author_short":["Herrero, M. J.","Velmeshev, D.","Hernandez-Pineda, D.","Sethi, S.","Sorrells, S.","Banerjee, P.","Sullivan, C.","Gupta, A. R","Kriegstein, A. R","Corbin, J. G"],"bibdata":{"bibtype":"article","type":"article","title":"Identification of amygdala-expressed genes associated with autism spectrum disorder","author":[{"propositions":[],"lastnames":["Herrero"],"firstnames":["Maria","Jesus"],"suffixes":[]},{"propositions":[],"lastnames":["Velmeshev"],"firstnames":["Dmitry"],"suffixes":[]},{"propositions":[],"lastnames":["Hernandez-Pineda"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Sethi"],"firstnames":["Saarthak"],"suffixes":[]},{"propositions":[],"lastnames":["Sorrells"],"firstnames":["Shawn"],"suffixes":[]},{"propositions":[],"lastnames":["Banerjee"],"firstnames":["Payal"],"suffixes":[]},{"propositions":[],"lastnames":["Sullivan"],"firstnames":["Catherine"],"suffixes":[]},{"propositions":[],"lastnames":["Gupta"],"firstnames":["Abha","R"],"suffixes":[]},{"propositions":[],"lastnames":["Kriegstein"],"firstnames":["Arnold","R"],"suffixes":[]},{"propositions":[],"lastnames":["Corbin"],"firstnames":["Joshua","G"],"suffixes":[]}],"abstract":"BACKGROUND: Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development. METHODS: Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD. RESULTS: Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline. LIMITATIONS: We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages. CONCLUSIONS: Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.","journal":"Mol Autism","volume":"11","number":"1","pages":"39","month":"May","year":"2020","keywords":"ASD genes; Amygdala; Autism spectrum disorder; Brain development; Single nucleus RNA sequencing","language":"en","bibtex":"@ARTICLE{Herrero2020-vo,\n title = \"Identification of amygdala-expressed genes associated with autism\n spectrum disorder\",\n author = \"Herrero, Maria Jesus and Velmeshev, Dmitry and Hernandez-Pineda,\n David and Sethi, Saarthak and Sorrells, Shawn and Banerjee, Payal\n and Sullivan, Catherine and Gupta, Abha R and Kriegstein, Arnold\n R and Corbin, Joshua G\",\n abstract = \"BACKGROUND: Studies of individuals with autism spectrum disorder\n (ASD) have revealed a strong multigenic basis with the\n identification of hundreds of ASD susceptibility genes. ASD is\n characterized by social deficits and a range of other phenotypes,\n implicating complex genetics and involvement of a variety of\n brain regions. However, how mutations and mis-expression of\n select gene sets are associated with the behavioral components of\n ASD remains unknown. We reasoned that for genes to be associated\n with ASD core behaviors they must be: (1) expressed in brain\n regions relevant to ASD social behaviors and (2) expressed during\n the ASD susceptible window of brain development. METHODS:\n Focusing on the amygdala, a brain region whose dysfunction has\n been highly implicated in the social component of ASD, we mined\n publicly available gene expression databases to identify\n ASD-susceptibility genes expressed during human and mouse\n amygdala development. We found that a large cohort of known ASD\n susceptibility genes is expressed in the developing human and\n mouse amygdala. We further performed analysis of single-nucleus\n RNA-seq (snRNA-seq) data from microdissected amygdala tissue from\n five ASD and five control human postmortem brains ranging in age\n from 4 to 20 years to elucidate cell type specificity of\n amygdala-expressed genes and their dysregulation in ASD. RESULTS:\n Our analyses revealed that of the high-ranking ASD susceptibility\n genes, 80 are expressed in both human and mouse amygdala during\n fetal to early postnatal stages of development. Our human\n snRNA-seq analyses revealed cohorts of genes with altered\n expression in the ASD amygdala postnatally, especially within\n excitatory neurons, with dysregulated expression of seven genes\n predicted from our datamining pipeline. LIMITATIONS: We were\n limited by the ages for which we were able to obtain human\n tissue; therefore, the results from our datamining pipeline\n approach will require validation, to the extent possible, in\n human tissue from earlier developmental stages. CONCLUSIONS: Our\n pipeline narrows down the number of amygdala-expressed genes\n possibly involved in the social pathophysiology of ASD. Our human\n single-nucleus gene expression analyses revealed that ASD is\n characterized by changes in gene expression in specific cell\n types in the early postnatal amygdala.\",\n journal = \"Mol Autism\",\n volume = 11,\n number = 1,\n pages = \"39\",\n month = may,\n year = 2020,\n keywords = \"ASD genes; Amygdala; Autism spectrum disorder; Brain development;\n Single nucleus RNA sequencing\",\n language = \"en\"\n}\n\n","author_short":["Herrero, M. J.","Velmeshev, D.","Hernandez-Pineda, D.","Sethi, S.","Sorrells, S.","Banerjee, P.","Sullivan, C.","Gupta, A. R","Kriegstein, A. R","Corbin, J. G"],"key":"Herrero2020-vo","id":"Herrero2020-vo","bibbaseid":"herrero-velmeshev-hernandezpineda-sethi-sorrells-banerjee-sullivan-gupta-etal-identificationofamygdalaexpressedgenesassociatedwithautismspectrumdisorder-2020","role":"author","urls":{},"keyword":["ASD genes; Amygdala; Autism spectrum disorder; Brain development; Single nucleus RNA sequencing"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://bibbase.org/f/EJMp3HRuxirjxpcXh/references.bib","dataSources":["sAFYeB74DpbdXM9NN","4zx9n2tbeLTix3Wxr","k3cdWrThyTh5o59Rm","hq9pebjzmsTuyxGGx","h8Atv2SAy4PmShg5j"],"keywords":["asd genes; amygdala; autism spectrum disorder; brain development; single nucleus rna sequencing"],"search_terms":["identification","amygdala","expressed","genes","associated","autism","spectrum","disorder","herrero","velmeshev","hernandez-pineda","sethi","sorrells","banerjee","sullivan","gupta","kriegstein","corbin"],"title":"Identification of amygdala-expressed genes associated with autism spectrum disorder","year":2020}