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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 F 2  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.

plos one

Fine Mapping and Candidate Gene Search of Quantitative Trait Loci for Growth and Obesity Using Mouse Intersubspecific Subcongenic Intercrosses and Exome Sequencing