Talk 7
Presenter: Elissa Chesler
Wednesday, 1:20pm

Genetics of Hippocampal Gene Expression in Diversity Outbred Mice

Narayanan Raghupathy, Ray F. Robledo, Daniel M Gatti, Steven C. Munger, Charles Phillips, Joel A. Graber, Matthew A. Hibbs, Michael A. Langston, Gary A. Churchill, Elissa J. Chesler
The Jackson Laboratory, Bar Harbor, Maine, Electrical Engineering and Computer Science, University of Tennessee, Knoxville, Tennessee, Trinity University, San Antonio, Texas.

The Diversity Outbred (DO) mouse population is produced from a pseudorandom intercross of the eight founders of Collaborative Cross (CC) inbred mouse strains. The resulting population has over 45 million segregating SNPs, high-recombinational precision and high behavioral diversity. Initial studies demonstrate that the DO mice provide high-resolution genetic mapping. To examine the genetics of gene expression and behavioral phenotypes, we sequenced the transcriptome from hippocampus of 258 DO mice using Illumina HiSeq 2000, genotyped at over 7500 SNPs across the genome. In the face of high genetic diversity in DO we employed an individualized diploid DO genome for read alignment and expression quantitation. These transcript abundances were subject to expression QTL analysis (eQTL) and combinatorial, genome wide gene co-expression analysis. The eQTL analysis shows that the majority of linkages are local, and that even when conditioning on these major local eQTL effects distal modifiers of expression were rarely detected with the present sample size. Gene co-expression analysis reveals a large number of small clusters relative to those observed in lower resolution populations. These clusters are functionally cohesive and can be related to behavioral phenomena and expression QTLs.