Fine mapping of a QTL region with large effects on growth and fatness on mouse chromosome 2

Abstract

We combined the use of a congenic line and recombinant progeny testing (RPT) to characterize and fine map a previously identified region of distal mouse chromosome 2 (MMU2) harboring quantitative trait loci (QTL) with large effects on growth and fatness. The congenic line [M16i.B6-( D2Mit306- D2Mit52); MB2] was created using an inbred line (M16i) derived from a line that had undergone long-term selection for rapid weight gain (M16) as the recipient for an ∼38-cM region on MMU2 from the inbred line C57BL/6J. A large F2 cohort (1,200 mice) originating from a cross between MB2 and M16i was created, and 40 F2 males with defined recombinations within the QTL region were used to produce 665 segregating progeny. Linkage analysis of the F2 population detected QTL with very large effects on body weight, body fat, lean tissue mass, bone mineral density, and liver weight. Confidence intervals of the QTL were narrowed to regions of 1.5–4.5 cM. Analysis of progeny of the recombinant F2 males confirmed the existence of the QTL and further contributed to localization of their map positions. These efforts confirmed the presence of QTL with major effect on MMU2, narrowed the estimated region harboring the QTL from 38 to 12 cM, and further characterized phenotypic effects of the QTL, effectively culminating in a significantly decreased pool of positional candidate genes potentially representing these genes controlling predisposition to growth and fatness.

Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors

“…Although this result would be anticipated, it is not clear whether the duplicated gene, which is truncated, is actually functional (37). Given the collective antimicrobial functions of genes within this cluster, an alternative explanation is that cumulative allelic variation in several candidate genes in this region accounts for the overall QTL effect, as has been previously observed for several QTL that were dissected into subregions through congenic analysis (38,39). The mapping power of our approach will increase as we continue into later generations of the AIL (now at G 10 ).…”

Genetic loci affecting body weight and fatness in a C57BL/6J × PWK/PhJ mouse intercross

“…The other region in which we searched for candidate genes was on mouse Chr 2, near D2Mit285, which maps between the midpoint of the chromosome and its telomere. Many studies have identified this distal region of Chr 2 as important in body composition phenotypes, and it is the focus of several positional cloning efforts (Chiu et al 2007;Diament et al 2004;Farber et al 2006;Jerez-Timaure et al 2005). According to our candidate gene analysis, the three genes most likely to underlie the QTL on Chr 2 were adenosine deaminase, cystatin C, and lipopolysaccharide binding protein.…”

“…Prior work in our laboratory has validated the DEXA method using a wide range of mouse strains (including B6 and PWK) and suggests that differences between this measure and other measures of body composition are minor. Previous investigators have used this method successfully to conduct genetic analyses of body composition in mice (Jerez-Timaure et al 2005;Masinde et al 2002c;Srivastava et al 2006;Vitarius et al 2006). …”

Emerging Roles of Atypical Dual Specificity Phosphatases in Cancer

“…DUSP15 displays phosphatase activity against the artificial substrate pNPP in vitro [130], but physiological substrates for DUSP15 have yet to be reported. DUSP15 contains an N-terminal myristoylation signal, resulting in targeting of the protein to plasma membrane [90] and in mice DUSP15 has been identified as a candidate gene in a quantitative trait locus (QTL) thought to harbor genes that control for the predisposition to growth and fatness in mice [131].…”