Global patterns of cis variation in human cells revealed by high-density allelic expression analysis
Global patterns of cis variation in human cells revealed by high-density allelic expression analysis
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DOI：
10.1038/ng.473
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发表时间：
2009-11-01
期刊：
影响因子：
30.8
通讯作者：
Pastinen, Tomi
中科院分区：
文献类型：
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作者：
Ge, Bing;Pokholok, Dmitry K.;Pastinen, Tomi
改变基因表达的顺式作用变体是表型差异的来源。表达变异的顺式作用组分可以通过等位基因表达（AE）差异的作图来鉴定，所述等位基因表达（AE）是两个等位基因转录物之间的相对表达的量度。我们使用Illumina Human 1 M BeadChips上AE的定量测量生成了AE相关SNP的图谱。在源自欧洲血统供体的53个淋巴母细胞样细胞系中，我们鉴定了影响30%（2935/9751）测量的RefSeq转录物的常见顺式变体，其排列显著性为0.001。顺式调节变体的普遍影响（其解释AE中>50%的群体变异）延伸至全长转录物及其同种型以及未注释的转录物。这些强大的影响，促进顺式调节SNPs的精细映射，如通过解剖8号染色体中系统性红斑狼疮相关C8 orf 13-BLK区域的转录本的遗传控制所证明的。密集收集的关联将有助于大规模分离顺式调节SNP。
Cis-acting variants altering gene expression are a source of phenotypic differences. The cis-acting components of expression variation can be identified through the mapping of differences in allelic expression (AE), which is the measure of relative expression between two allelic transcripts. We generated a map of AE associated SNPs using quantitative measurements of AE on Illumina Human1M BeadChips. In 53 lymphoblastoid cell lines derived from donors of European descent, we identified common cis variants affecting 30% (2935/9751) of the measured RefSeq transcripts at 0.001 permutation significance. The pervasive influence of cis-regulatory variants, which explain >50% of population variation in AE, extend to full-length transcripts and their isoforms as well as to unannotated transcripts. These strong effects facilitate fine mapping of cis-regulatory SNPs, as demonstrated by dissection of heritable control of transcripts in the systemic lupus erythematosus-associated C8orf13-BLK region in chromosome 8. The dense collection of associations will facilitate large-scale isolation of cis-regulatory SNPs.