Presenter: Narayanan Raghupathy
Narayanan Raghupathy, K. B. Choi, Ron Korstanje, Fernando Pardo Manuel de Villena and Gary Churchill The Jackson Laboratory, Bar Harbor, ME 04609 Department of Genetics, University of North Carolina, Chapel Hill, NC 27599
Allele specific gene expression (ASE), the preferential expression of one allele over the other, is an important phenotype of gene expression and regulation. ASE could be due to local genetic variations or due to parent-of-origin effects. In model organisms, recent studies on ASE using RNA-seq technology have shown conflicting degrees and causes. A key challenge in using RNA-seq technology for understanding ASE is accurately quantifying it, as alignment biases can lead to wrong estimate of allele specificity. We present a novel approach EMASE, based on expectation-maximization (EM) algorithm, to accurately quantify ASE from RNA-seq data from F1 cross. Our approach utilizes the genetic variations in the transcriptomes of the parental strains and uses RNA-seq alignments to both the parental transcriptomes to accurately estimate ASE. To understand the extent of allele specific expression due to local genetics and imprinting, and effect of diet and age on ASE, we crossed two divergent inbred mouse strains NOD/ShiLtJ and PWK/PhJ in both directions under two diets; vitamin D and Methionine, and age groups, with 6 biological replicates. We sequenced the liver mRNA samples using Illumina GAIIx. Our results show that ASE is prevalent across the genome. The primary driver of ASE is local genotype. Most of the genes showing parent-of-origin effect are known imprinted genes. Methionine diet had a strong effect on ASE, while the vitamin D diet had little effect on ASE.