detection of parent-of-origin specific expression quantitative trait loci by cis-association analysis of gene expression in trios检测cis-association parent-of-origin具体表达数量性状位点的基因表达分析在三人小组.pdfVIP

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detection of parent-of-origin specific expression quantitative trait loci by cis-association analysis of gene expression in trios检测cis-association parent-of-origin具体表达数量性状位点的基因表达分析在三人小组.pdf

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detection of parent-of-origin specific expression quantitative trait loci by cis-association analysis of gene expression in trios检测cis-association parent-of-origin具体表达数量性状位点的基因表达分析在三人小组

Detection of Parent-of-Origin Specific Expression Quantitative Trait Loci by Cis-Association Analysis of Gene Expression in Trios Paras Garg, Christelle Borel, Andrew J. Sharp* Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America Abstract Parent-of-origin (PofO) effects, such as imprinting are a phenomenon in which homologous chromosomes exhibit differential gene expression and epigenetic modifications according to their parental origin. Such non-Mendelian inheritance patterns are generally ignored by conventional association studies, as these tests consider the maternal and paternal alleles as equivalent. To identify regulatory regions that show PofO effects on gene expression (imprinted expression Quantitative Trait Loci, ieQTLs), here we have developed a novel method in which we associate SNP genotypes of defined parental origin with gene expression levels. We applied this method to study 59 HapMap phase II parent- offspring trios. By analyzing mother/father/child trios, rules of Mendelian inheritance allowed the parental origin to be defined for ,95% of SNPs in each child. We used 680,475 informative SNPs and corresponding expression data for 92,167 probe sets from Affymetrix GeneChip Human Exon 1.0 ST arrays and performed four independent cis-association analyses with the expression level of RefSeq genes within 1 Mb using PLINK. Independent analyses of maternal and paternal genotypes identified two significant cis-ieQTLs (p,1027) at which expression of genes SFT2D2 and SRRT associated exclusively with maternally inherited SNPs rs3753292 and rs6945374, respectively. 28 additional suggestive cis-associations with on