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Unraveling the regulatory mechanisms underlying tissue-dependent genetic variation of gene expression
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نویسنده
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fu j. ,wolfs m.g.m. ,deelen p. ,westra h.-j. ,fehrmann r.s.n. ,te meerman g.j. ,buurman w.a. ,rensen s.s.m. ,groen h.j.m. ,weersma r.k. ,van den berg l.h. ,veldink j. ,ophoff r.a. ,snieder h. ,van heel d. ,jansen r.c. ,hofker m.h. ,wijmenga c. ,franke l.
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منبع
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plos genetics - 2012 - دوره : 8 - شماره : 1
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چکیده
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It is known that genetic variants can affect gene expression,but it is not yet completely clear through what mechanisms genetic variation mediate this expression. we therefore compared the cis-effect of single nucleotide polymorphisms (snps) on gene expression between blood samples from 1,240 human subjects and four primary non-blood tissues (liver,subcutaneous,and visceral adipose tissue and skeletal muscle) from 85 subjects. we characterized four different mechanisms for 2,072 probes that show tissue-dependent genetic regulation between blood and non-blood tissues: on average 33.2% only showed cis-regulation in non-blood tissues; 14.5% of the eqtl probes were regulated by different,independent snps depending on the tissue of investigation. 47.9% showed a different effect size although they were regulated by the same snps. surprisingly,we observed that 4.4% were regulated by the same snp but with opposite allelic direction. we show here that snps that are located in transcriptional regulatory elements are enriched for tissue-dependent regulation,including snps at 3′ and 5′ untranslated regions (p = 1.84×10 -5 and 4.7×10 -4,respectively) and snps that are synonymous-coding (p = 9.9×10 -4). snps that are associated with complex traits more often exert a tissue-dependent effect on gene expression (p = 2.6×10 -10). our study yields new insights into the genetic basis of tissue-dependent expression and suggests that complex trait associated genetic variants have even more complex regulatory effects than previously anticipated. © 2012 fu et al.
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آدرس
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department of genetics,university medical center groningen,university of groningen,groningen,netherlands,department of epidemiology,university medical center groningen,university of groningen,groningen, Netherlands, department of pathology and medical biology,molecular genetics,university medical center groningen,university of groningen,groningen, Netherlands, hanze university groningen,groningen, Netherlands, department of genetics,university medical center groningen,university of groningen,groningen, Netherlands, department of genetics,university medical center groningen,university of groningen,groningen,netherlands,department of medical oncology,university medical center groningen,university of groningen,groningen, Netherlands, department of genetics,university medical center groningen,university of groningen,groningen, Netherlands, department of surgery,university hospital maastricht and nutrition and toxicology research institute (nutrim),maastricht university,maastricht, Netherlands, department of surgery,university hospital maastricht and nutrition and toxicology research institute (nutrim),maastricht university,maastricht, Netherlands, department of pulmonology,university medical centre groningen,university of groningen,groningen, Netherlands, department of gastroenterology and hepatology,university medical center groningen,university of groningen,groningen, Netherlands, department of neurology,rudolf magnus institute of neuroscience,university medical center utrecht,utrecht, Netherlands, department of neurology,rudolf magnus institute of neuroscience,university medical center utrecht,utrecht, Netherlands, department of medical genetics,university medical center utrecht,utrecht, Netherlands, department of epidemiology,university medical center groningen,university of groningen,groningen, Netherlands, blizard institute of cell and molecular science,barts,the london school of medicine and dentistry,queen mary university of london,london, United Kingdom, groningen bioinformatics centre,groningen biomolecular sciences and biotechnology institute,university of groningen,haren, Netherlands, department of pathology and medical biology,molecular genetics,university medical center groningen,university of groningen,groningen, Netherlands, department of genetics,university medical center groningen,university of groningen,groningen, Netherlands, department of genetics,university medical center groningen,university of groningen,groningen, Netherlands
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Authors
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