Genome-wide isolation of growth and obesity QTL using mouse speed congenic strains

Abstract

BackgroundHigh growth (hg) modifier and background independent quantitative trait loci (QTL) affecting growth, adiposity and carcass composition were previously identified on mouse chromosomes (MMU) 1, 2, 5, 8, 9, 11 and 17. To confirm and further characterize each QTL, two panels of speed congenic strains were developed by introgressing CAST/EiJ (CAST) QTL alleles onto either mutant C57Bl/6J-hg/hg (HG) or wild type C57Bl/6J (B6) genetic backgrounds.ResultsThe first speed congenic panel was developed by introgressing four overlapping donor regions spanning MMU2 in its entirety onto both HG and B6 backgrounds, for a total of eight strains. Phenotypic characterization of the MMU2 panel confirmed the segregation of multiple growth and obesity QTL and strongly suggested that a subset of these loci modify the effects of the hg deletion. The second panel consisted of individual donor regions on an HG background for each QTL on MMU1, 5, 8, 9, 11 and 17. Of the six developed strains, five were successfully characterized and displayed significant differences in growth and/or obesity as compared to controls. All five displayed phenotypes similar to those originally attributed to each QTL, however, novel phenotypes were unmasked in several of the strains including sex-specific effects.ConclusionThe speed congenic strains developed herein constitute an invaluable genomic resource and provide the foundation to identify the specific nature of genetic variation influencing growth and obesity.

Bayesian genome-wide association analysis of growth and yearling ultrasound measures of carcass traits in Brangus heifers

“…There are several other genes known to be components of the GH-IGF axis that map to this region of chromosome 5. Farber et al (2006) described these genes within a manually drawn GenMAPP image, which included the genes of IGFBP6, STAT2 and 6, and SOCS2. The STAT (i.e., signal transducer and activator of transcription) and SOCS (suppressor of cytokine signaling 2) proteins are involved in cell signaling cascades, subsequent to hormones, such as GH binding their receptors (Rawlings et al, 2004;Schindler and Plumlee, 2008;Ahmed and Farquharson, 2010).…”

Evidence of maternal QTL affecting growth and obesity in adult mice

“…During the development of chromosome 2 subcongenic strains, mice were genotyped for 36 microsatellite loci ( D2Mit329 , D2Mit93 , D2Mit94 , D2Mit160 , D2Mit476 , D2Mit15 , D2Mit439 , D2Mit130 , D2Mit389 , D2Mit43 , D2Mit477 , D2Mit185 , D2Mit58 , D2Mit207 , D2Mit101 , D2Mit420 , D2Mit445 , D2Mit17 , D2Mit224 , D2Mit107 , D2Mit488 , D2Mit223 , D2Mit136 , D2Mit490 , D2Mit212 , D2Mit194 , D2Ucd22 , D2Mit260 , D2Mit286 , D2Mit409 , D2Mit262 , D2Mit196 , D2Mit342 , D2Mit456 , D2Mit213 , and D2Mit148 ; Table 1 ) and the nonagouti locus. DNA samples were isolated from 1.0-mm tail clips and genotyped following standard PCR protocols as described by Farber et al ( 2006 ). Chromosome 7 subcongenic strains were genotyped by standard PCR protocols for ten microsatellite loci ( D7Mit318 , D7Mit90 , D7Mit62 , D7Mit301 , D7Mit373 , D7Mit321 , D7Mit354 , D7Mit353 , D7Mit96 , and D7Mit37 ; Table 1 ) after extracting DNA samples from kidney or toe (Diament and Warden 2004 ).…”

“…For mouse chromosome 2, seven subcongenic strains were developed from the B6.CAST-( D2Mit329-D2Mit457 )N(6) congenic strain (B62D) (Farber and Medrano 2007 ; Farber et al 2006 ). Five additional subcongenic strains were generated on the basis of the HG.CAST-( D2Mit329-D2Mit457 )N(6) congenic line (HG2D) (R. J. Gularte, personal communication), following the procedures detailed by Farber and Medrano ( 2007 ).…”

Calcium taste preferences: genetic analysis and genome screen of C57BL/6J × PWK/PhJ hybrid mice

“…Using a DLOD ! 3.1 as a criterion (Farber et al 2006), there were no sexrelated effects in any analysis so sex was not included as a factor in the results reported here.…”