Fine Mapping of Mouse QTLs for Fatness Using SNP Data

Abstract

Quantitative trait loci (QTLs), as determined in crossbred studies, are a valuable resource to identify genes responsible for the corresponding phenotypic variances. Due to their broad chromosomal extension of some dozens of megabases, further steps are necessary to bring the number of candidate genes that underlie the detected effects to a reasonable order of magnitude. We use a set of 13,370 SNPs to identify informative haplotype blocks in 22 mouse QTLs for fatness. About half of the genes in a typical QTL overlap with haplotype blocks, which are different for the two base mouse lines, and which, thus, qualify for further analysis. For these genes we collect four more pieces of evidence for association with fat accumulation, namely (1) homology to genes identified in a Caenorhabditis elegans knock-out experiment as fat decreasing or fat increasing, (2) the overexpression of the genes in mouse fat, liver, muscle, or hypothalamus tissues, (3) the occurrence of a gene in several independently found QTLs, and (4) the information provided by gene ontology, to achieve a ranked list of 131 candidate genes. Ten genes fulfill three or four of the above sketched criteria and are discussed briefly, 121 further genes fulfilling two criteria are provided as on-line material. Viewing the genomic region of fatness-related QTLs under several different aspects is appropriate to assess the many thousands of genes that reside in such QTLs and to produce lists of more robust candidate genes.