Genome-wide analysis of transcript isoform variation in humans

We have performed a genome-wide analysis of common genetic variation controlling differential expression of transcript isoforms in the CEU HapMap population using a comprehensive exon tiling microarray covering 17,897 genes. We detected 324 genes with significant associations between flanking SNPs and transcript levels. Of these, 39% reflected changes in whole gene expression and 55% reflected transcript isoform changes such as splicing variants (exon skipping, alternate splice site usage, intron retention), differential 5’ UTR (initiation of transcription) usage, and differential 3’ UTR (alternative polyadenylation) usage. These results demonstrate that the regulatory effects of genetic variation in a normal human population are drastically more complex than previously observed. This additional layer of molecular diversity may account for natural phenotypic variation and disease susceptibility. Keywords: Comparative genomic hybridiation within the CEU HapMap population We used individuals from the HapMap CEU population for our analysis of examining genetic variation in transcript isoforms. 3 biological growths each from 57 individuals (parents of CEU trios) were used.