cis sequence effects on gene expression

We generated gene expression profiling data at N = 697 candidate genes from N = 30 lymphoblastoid cell lines for this study and used available candidate gene resequencing data at N = 552 candidate genes to identify N = 30 candidate genes with sufficient variance in both datasets for the investigation of cis sequence effects. We used two additive models and the haplotype phylogeny scanning approach of Templeton (Tree Scanning) to evaluate association between individual SNPs, all SNPs at a gene, and diplotypes, with log-transformed gene expression. SNPs and diplotypes at eight candidate genes exhibited statistically significant (p < 0.05) association with gene expression. Using the literature as a "gold standard" to compare 14 genes with data from both this study and the literature, we observed 80% and 85% concordance for genes exhibiting and not exhibiting significant cis sequence effects in our study, respectively.Based on analysis of our results and the extant literature, one in four genes exhibits significant cis sequence effects, and for these genes, about 30% of gene expression variation is accounted for by cis sequence variation. Despite diverse experimental approaches, the presence or absence of significant cis sequence effects is largely supported by previously published studies.Among heritable factors that influence phenotypic expression are sequence polymorphisms in genic regions that affect gene expression rather than protein structure [1,2]. The influence of sequence variation linked to the gene sequence on the regulation of gene expression (cis sequence effects) has been studied experimentally in H. sapiens at single genes for decades [3], and, more recently, in various multi-gene approaches in S. cerevisiae [4-6], S. purpuratus [7,8], D. melanogaster and D. simulans [9,10], M. musculus [11,12], Z. mays [12], and H. sapiens [12-24]. In studies with human tissues, these efforts have characterized cis sequence effects on gene expression as common and herit