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Abundant quantitative trait loci exist for DNA methylation and gene expression in Human Brain
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نویسنده
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gibbs j.r. ,van der brug m.p. ,hernandez d.g. ,traynor b.j. ,nalls m.a. ,lai s.-l. ,arepalli s. ,dillman a. ,rafferty i.p. ,troncoso j. ,johnson r. ,zielke h.r. ,ferrucci l. ,longo d.l. ,cookson m.r. ,singleton a.b.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 5 - صفحه:29
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چکیده
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A fundamental challenge in the post-genome era is to understand and annotate the consequences of genetic variation,particularly within the context of human tissues. we present a set of integrated experiments that investigate the effects of common genetic variability on dna methylation and mrna expression in four human brain regions each from 150 individuals (600 samples total). we find an abundance of genetic cis regulation of mrna expression and show for the first time abundant quantitative trait loci for dna cpg methylation across the genome. we show peak enrichment for cis expression qtls to be approximately 68,000 bp away from individual transcription start sites; however,the peak enrichment for cis cpg methylation qtls is located much closer,only 45 bp from the cpg site in question. we observe that the largest magnitude quantitative trait loci occur across distinct brain tissues. our analyses reveal that cpg methylation quantitative trait loci are more likely to occur for cpg sites outside of islands. lastly,we show that while we can observe individual qtls that appear to affect both the level of a transcript and a physically close cpg methylation site,these are quite rare. we believe these data,which we have made publicly available,will provide a critical step toward understanding the biological effects of genetic variation.
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آدرس
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laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md,united states,department of molecular neuroscience and reta lila weston laboratories,institute of neurology,university college london,london, United Kingdom, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md,united states,department of molecular and integrative neurosciences,the scripps research institute,jupiter,fl, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md,united states,department of molecular neuroscience and reta lila weston laboratories,institute of neurology,university college london,london, United Kingdom, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md,united states,department of molecular neuroscience and reta lila weston laboratories,institute of neurology,university college london,london, United Kingdom, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, division of neuropathology,department of pathology,school of medicine,johns hopkins university,baltimore,md, United States, national institute of child heath,human development brain and tissue bank for developmental disorders,university of maryland medical school,baltimore,md, United States, national institute of child heath,human development brain and tissue bank for developmental disorders,university of maryland medical school,baltimore,md, United States, clinical research branch,national institute on aging,baltimore,md, United States, lymphocyte cell biology unit,laboratory of immunology,national institute on aging,national institutes of health,baltimore,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States, laboratory of neurogenetics,national institute on aging,national institutes of health,bethesda,md, United States
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Authors
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