HapMap CEU parent custom array expression

The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe (CEPH) using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, chromosome 21 and chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, False Discovery Rate and permutations. For the 374 expressed genes, we find many regions with statistically significant association of SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis-) to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5 kb (phase I) HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level. Keywords: Gene expression, Lymphoblastoid, Gene expression of lymphoblastoid cell lines from the 60 HapMap CEU parents was quantified with a custom Illumina bead array (see above). Two (Ambion Message Amp II) IVT reactions were performed for each cell line and each IVT was hybridised to 3 or 5 arrays, so that each sample had either 6 or 8 replicates. Arrays were run in 96-well plate format (SAM). Each array was made from a bead pool containing 1433 unique bead types (each with a unique 50mer probe). On average an array contains 30 of each bead distributed at random.