Genetic control of heart weight in mouse and man (697.4)

Abstract

Heart weight (HW) serves not only measure of cardiac structure and function, and also as an intermediate phenotype for cardiovascular disease outcome. In humans HW is a heritable trait and has been linked to several genetic loci. Genome‐wide association study (GWAS) have identified single‐nucleotide polymorphisms in and near genes that may contribute to variability in HW. The BXD family of recombinant inbred strains comprise a large panel of isogenic but diverse strain derived by crossing C57BL/6J and DBA/2J. This genetic reference panel is a remarkable resource because genotype data (high density SNP markers) is available in GeneNetwork database; and the genomes of both parents have been sequenced. Our goal is to define genetic loci and candidate genes that control HW. There is significant variation in HW among the BXD strains_from 81 to 182 mg. A locus in chromosome 3 is responsive for a significant fraction (70%) of HW variation. The expression of candidate genes in this locus was studied using whole transcriptome analysis and qPCR for the parent strains. Morphometric measurement of the parent strains was used to evaluate the causes of HW variation. Candidate genes were compared with genes identified in GWAS. Several candidate genes in our study related with candidate genes identified in human GWAS. The best candidate genes based on this synthesis of human and mouse data include KCND3, KCNA3, SLC16A4, DDX20, and OVGP1.Grant Funding Source: NIH