Abstract
Although growth and body composition traits are quantitative traits of medical and agricultural importance, the genetic and molecular basis of those traits remains elusive. Our previous genome-wide quantitative trait locus (QTL) analyses in an intersubspecific backcross population between C57BL/6JJcl (B6) and wild Mus musculus castaneus mice revealed a major growth QTL (named Pbwg1) on a proximal region of mouse chromosome 2. Using the B6.Cg-Pbwg1 intersubspecific congenic strain created, we revealed 12 closely linked QTLs for body weight and body composition traits on an approximately 44.1-Mb wild-derived congenic region. In this study, we narrowed down genomic regions harboring three (Pbwg1.12, Pbwg1.3 and Pbwg1.5) of the 12 linked QTLs and searched for possible candidate genes for the QTLs. By phenotypic analyses of F2 intercross populations between B6 and each of four B6.Cg-Pbwg1 subcongenic strains with overlapping and non-overlapping introgressed regions, we physically defined Pbwg1.12 affecting body weight to a 3.8-Mb interval (61.5–65.3 Mb) on chromosome 2. We fine-mapped Pbwg1.3 for body length to an 8.0-Mb interval (57.3–65.3) and Pbwg1.5 for abdominal white fat weight to a 2.1-Mb interval (59.4–61.5). The wild-derived allele at Pbwg1.12 and Pbwg1.3 uniquely increased body weight and length despite the fact that the wild mouse has a smaller body size than that of B6, whereas it decreased fat weight at Pbwg1.5. Exome sequencing and candidate gene prioritization suggested that Gcg and Grb14 are putative candidate genes for Pbwg1.12 and that Ly75 and Itgb6 are putative candidate genes for Pbwg1.5. These genes had nonsynonymous SNPs, but the SNPs were predicted to be not harmful to protein functions. These results provide information helpful to identify wild-derived quantitative trait genes causing enhanced growth and resistance to obesity.
Highlights
Body weight and body composition traits, including fat and organ weight, are quantitative in nature and are controlled by multiple genetic loci, referred to as quantitative trait locus (QTL), environmental factors and their interactions
We previously discovered many QTLs for postnatal body weight and growth from an untapped resource of wild M. m. castaneus mice captured live in the Philippines, by genome-wide QTL analyses in an intersubspecific backcross population between C57BL/6JJcl (B6) inbred mice and the wild castaneus mice [16,17,18]
We developed more than 20 subcongenic strains derived from B6.Cg-Pbwg1
Summary
Body weight and body composition traits, including fat and organ weight, are quantitative in nature and are controlled by multiple genetic loci, referred to as QTLs (quantitative trait loci), environmental factors and their interactions. They are important economic traits in livestock [1]. Modern broiler chickens have been intensively selected for rapid growth rate, but they display excessive deposition of body fat. Thousands of QTLs affecting various quantitative traits have been mapped to many chromosomal regions of the mouse and have been deposited in the Mouse Genome Database (MGD, release 5.19, August 2014) [5]
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