来自MuTHER(人类基因和组织表达的多样性)国际合作项目的研究人员报道了来自大约850个同卵和异卵双胞胎的三种组织(脂肪组织、皮肤和血细胞)的基因表达的遗传分析结果。他们系统性地剖析了影响基因表达的遗传学因素(顺式作用和反式作用),并评估了影响基因表达的非遗传学因素。相关的研究论文于9月2日在线发表在《Nature Genetics》期刊上。

-2012年10月《自然-遗传》

中文翻译


【题目】研究定位双胞胎多组织的顺式和反式调控效应

【译文】基因表达中基于序列的突变是疾病发生的关键驱动因素。在许多表达数量性状位点(eQTL)研究中,顺式作用中调控基因表达的常见突变已经得到定位,尤其在来自不相关个体的单一组织中。本研究收集了大量同卵和异卵双胞胎的多种组织(包括脂肪组织、皮肤和血细胞),综合分析了这些组织的基因表达水平,使得研究人员能够对影响基因表达的遗传学(顺式作用和反式作用)和非遗传学因素进行系统性的剖析。使用等同继承模型分析,本研究组发现至少40%可遗传的、影响基因表达的顺式作用不能用常见顺式突变来解释,这揭示了低频率的遗传贡献发现,及与转录调控和复杂性状敏感性都有关的罕见调控变异。本研究组认为大部分的基因表达遗传可能性是反式作用于结构基因的,本研究还鉴定到一些以组织限制性的方式起主要作用的重复的反式突变,它们可能可以调控许多基因的转录过程。

英文原稿


[Title]: Mapping cis- and trans-regulatory effects across multiple tissues in twins

[Authors]: Elin Grundberg, Kerrin S Small, Åsa K Hedman, Alexandra C Nica, Alfonso Buil, Sarah Keildson, Jordana T Bell, Tsun-Po Yang, Eshwar Meduri, Amy Barrett, James Nisbett, Magdalena Sekowska, Alicja Wilk, So-Youn Shin, Daniel Glass, Mary Travers, Josine L Min, Sue Ring, Karen Ho, Gudmar Thorleifsson, Augustine Kong, Unnur Thorsteindottir, Chrysanthi Ainali, Antigone S Dimas, Neelam Hassanali, Catherine Ingle, David Knowles, Maria Krestyaninova, Christopher E Lowe, Paola Di Meglio, Stephen B Montgomery, Leopold Parts, Simon Potter, Gabriela Surdulescu, Loukia Tsaprouni, Sophia Tsoka, Veronique Bataille, Richard Durbin, Frank O Nestle, Stephen O’Rahilly, Nicole Soranzo, Cecilia M Lindgren, Krina T Zondervan, Kourosh R Ahmadi, Eric E Schadt, Kari Stefansson, George Davey Smith, Mark I McCarthy, Panos Deloukas, Emmanouil T Dermitzakis, Tim D Spector & The Multiple Tissue Human Expression Resource (MuTHER) Consortium

[Abstract]: Sequence-based variation in gene expression is a key driver of disease risk. Common variants regulating expression in cis have been mapped in many expression quantitative trait locus (eQTL) studies, typically in single tissues from unrelated individuals. Here, we present a comprehensive analysis of gene expression across multiple tissues conducted in a large set of mono- and dizygotic twins that allows systematic dissection of genetic (cis and trans) and non-genetic effects on gene expression. Using identity-by-descent estimates, we show that at least 40% of the total heritable cis effect on expression cannot be accounted for by common cis variants, a finding that reveals the contribution of low-frequency and rare regulatory variants with respect to both transcriptional regulation and complex trait susceptibility. We show that a substantial proportion of gene expression heritability is trans to the structural gene, and we identify several replicating trans variants that act predominantly in a tissue-restricted manner and may regulate the transcription of many genes.

原文地址

http://www.nature.com/ng/journal/v44/n10/abs/ng.2394.html

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201212/nature-genetics-eqtl-disease-tendentiousness-regulatory-mutation-twins/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


一 × 5 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息