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.

Highlights

  • High growth 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

  • The speed congenic strains developed constitute an invaluable genomic resource and provide the foundation to identify the specific nature of genetic variation influencing growth and obesity

  • The MMU2 panel consisted of eight congenic strains developed by introgressing four overlapping donor regions onto both B6 and HG genetic backgrounds (Table 1)

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Summary

Introduction

High 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. The use of mouse models has provided valuable insight into the etiology of monogenic syndromes caused by single gene mutations Such models do not mimic the genetic complexity of disease traits commonly seen in the human population. Complex traits, such as polygenic growth and obesity are influenced by the small to moderate direct effects of quantitative trait loci (QTL), epistasis between QTL alleles, environmental perturbations and QTL-environment interactions. One resource used to fine map QTL are congenic strains which are designed to convert a complex polygenic trait into one that is mono- or oligogenic This is accomplished by eliminating segregating genetic variation outside the locus of interest and reducing the environmental variation influencing a trait by characterizing large numbers of genetically identical mice.

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