Dimas Antigone S, Deutsch Samuel, Stranger Barbara E, Montgomery Stephen B, Borel Christelle, Attar-Cohen Homa, Ingle Catherine, Beazley Claude, Gutierrez Arcelus Maria, Sekowska Magdalena, Gagnebin Marilyne, Nisbett James, Deloukas Panos, Dermitzakis Emmanouil T, Antonarakis Stylianos E
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1HH, Cambridge, UK.
Science. 2009 Sep 4;325(5945):1246-50. doi: 10.1126/science.1174148. Epub 2009 Jul 30.
Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity.
将基因变异与基因表达相关联的研究有助于解释常见的人类表型和疾病。由于功能变异可能以组织依赖的方式起作用，我们对75名个体的三种细胞类型进行了基因表达谱分析，并将其与基因变异（单核苷酸多态性）进行关联。我们检测到细胞类型特异性的遗传效应，69%至80%的调控变异以细胞类型特异性的方式起作用，并鉴定出每个基因有多个表达数量性状位点（eQTL），这些位点在细胞类型之间是独特的或共享的，并且与每个基因的转录本数量呈正相关。细胞类型特异性的eQTL在距离基因较远的位置被发现，且效应大小较小，类似于已知的增强子。这些数据表明，完整的调控变异库只能在细胞类型特异性的背景下被揭示。
