A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression. Farrell, J. J., Sherva, R. M., Chen, Z., Luo, H., Chu, B. F., Ha, S. Y., Li, C. K., Lee, A. C. W., Li, R. C. H., Li, C. K., Yuen, H. L., So, J. C. C., Ma, E. S. K., Chan, L. C., Chan, V., Sebastiani, P., Farrer, L. A., Baldwin, C. T., Steinberg, M. H., & Chui, D. H. K. Blood, 117(18):4935–4945, May, 2011. ![A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.
@article{farrell_3-bp_2011,
title = {A 3-bp deletion in the {HBS1L}-{MYB} intergenic region on chromosome 6q23 is associated with {HbF} expression},
volume = {117},
issn = {0006-4971},
url = {https://doi.org/10.1182/blood-2010-11-317081},
doi = {10.1182/blood-2010-11-317081},
abstract = {Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5\%; that resulting from the BCL11A polymorphism is 6.4\%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.},
number = {18},
urldate = {2021-06-02},
journal = {Blood},
author = {Farrell, John J. and Sherva, Richard M. and Chen, Zhi-yi and Luo, Hong-yuan and Chu, Benjamin F. and Ha, Shau Yin and Li, Chi Kong and Lee, Anselm C. W. and Li, Rever C. H. and Li, Chi Keung and Yuen, Hui Leung and So, Jason C. C. and Ma, Edmond S. K. and Chan, Li Chong and Chan, Vivian and Sebastiani, Paola and Farrer, Lindsay A. and Baldwin, Clinton T. and Steinberg, Martin H. and Chui, David H. K.},
month = may,
year = {2011},
pages = {4935--4945},
}
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By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.","number":"18","urldate":"2021-06-02","journal":"Blood","author":[{"propositions":[],"lastnames":["Farrell"],"firstnames":["John","J."],"suffixes":[]},{"propositions":[],"lastnames":["Sherva"],"firstnames":["Richard","M."],"suffixes":[]},{"propositions":[],"lastnames":["Chen"],"firstnames":["Zhi-yi"],"suffixes":[]},{"propositions":[],"lastnames":["Luo"],"firstnames":["Hong-yuan"],"suffixes":[]},{"propositions":[],"lastnames":["Chu"],"firstnames":["Benjamin","F."],"suffixes":[]},{"propositions":[],"lastnames":["Ha"],"firstnames":["Shau","Yin"],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Chi","Kong"],"suffixes":[]},{"propositions":[],"lastnames":["Lee"],"firstnames":["Anselm","C.","W."],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Rever","C.","H."],"suffixes":[]},{"propositions":[],"lastnames":["Li"],"firstnames":["Chi","Keung"],"suffixes":[]},{"propositions":[],"lastnames":["Yuen"],"firstnames":["Hui","Leung"],"suffixes":[]},{"propositions":[],"lastnames":["So"],"firstnames":["Jason","C.","C."],"suffixes":[]},{"propositions":[],"lastnames":["Ma"],"firstnames":["Edmond","S.","K."],"suffixes":[]},{"propositions":[],"lastnames":["Chan"],"firstnames":["Li","Chong"],"suffixes":[]},{"propositions":[],"lastnames":["Chan"],"firstnames":["Vivian"],"suffixes":[]},{"propositions":[],"lastnames":["Sebastiani"],"firstnames":["Paola"],"suffixes":[]},{"propositions":[],"lastnames":["Farrer"],"firstnames":["Lindsay","A."],"suffixes":[]},{"propositions":[],"lastnames":["Baldwin"],"firstnames":["Clinton","T."],"suffixes":[]},{"propositions":[],"lastnames":["Steinberg"],"firstnames":["Martin","H."],"suffixes":[]},{"propositions":[],"lastnames":["Chui"],"firstnames":["David","H.","K."],"suffixes":[]}],"month":"May","year":"2011","pages":"4935–4945","bibtex":"@article{farrell_3-bp_2011,\n\ttitle = {A 3-bp deletion in the {HBS1L}-{MYB} intergenic region on chromosome 6q23 is associated with {HbF} expression},\n\tvolume = {117},\n\tissn = {0006-4971},\n\turl = {https://doi.org/10.1182/blood-2010-11-317081},\n\tdoi = {10.1182/blood-2010-11-317081},\n\tabstract = {Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese β-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5\\%; that resulting from the BCL11A polymorphism is 6.4\\%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.},\n\tnumber = {18},\n\turldate = {2021-06-02},\n\tjournal = {Blood},\n\tauthor = {Farrell, John J. and Sherva, Richard M. and Chen, Zhi-yi and Luo, Hong-yuan and Chu, Benjamin F. and Ha, Shau Yin and Li, Chi Kong and Lee, Anselm C. W. and Li, Rever C. H. and Li, Chi Keung and Yuen, Hui Leung and So, Jason C. C. and Ma, Edmond S. K. and Chan, Li Chong and Chan, Vivian and Sebastiani, Paola and Farrer, Lindsay A. and Baldwin, Clinton T. and Steinberg, Martin H. and Chui, David H. 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