Genome-wide search for exonic variants affecting translational efficiency

To date, the search for expression quantitative trait loci (eQTL) has centered entirely on transcription; variants with effects on mRNA translation have not been systematically studied. We tested the use of ribosomal association as proxy for translational efficiency of polymorphic mRNAs to develop a novel high throughput approach for translational cis-regulation in the human genome. Cell lysates of lymphoblastoid cell lines (LCL) from 38 parents of the European HapMap set (CEU) were subjected to ultracentrifugal fractionation to separate polysomal/nonpolysomal mRNA. The ratio of polysomal/nonpolysomal mRNA level was taken as a proxy for translational efficiency and tested as a quantitative trait for association with single-nucleotide polymorphisms (SNPs) on the same mRNA transcript. Supplementary file “logTIfolds38CEUparents.txt” lists the polysomal/nonpolysomal mRNA level ratios, ready for QTL testing. Genotyping information is available on the HapMap or 1000 Genome websites. Besides the 38 parents of the European HapMap set, a few other samples were included for QC purposes. These other samples include one child, and three samples from the CEPH (PLATE II).