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Mamm Genome DOI:10.1007/s00335-010-9247-9

Genetic resistance to diet-induced obesity in chromosome substitution strains of mice.

Publication TypeJournal Article
Year of Publication2010
AuthorsBurrage, LC, Baskin-Hill, AE, Sinasac, DS, Singer, JB, Croniger, CM, Kirby, A, Kulbokas, EJ, Daly, MJ, Lander, ES, Broman, KW, Nadeau, JH
JournalMamm Genome
Date Published2010 Apr
KeywordsAlleles, Animals, Body Size, Chromosomes, Mammalian, Crosses, Genetic, Diet, Female, Genome, Inheritance Patterns, Male, Mice, Mice, Mutant Strains, Obesity, Quantitative Trait Loci, Quantitative Trait, Heritable, Reproducibility of Results, Time Factors, Weight Gain

Discovery of genes that confer resistance to diseases such as diet-induced obesity could have tremendous therapeutic impact. We previously demonstrated that the C57BL/6J-Chr(A/J)/NaJ panel of chromosome substitution strains (CSSs) is a unique model for studying resistance to diet-induced obesity. In the present study, three replicate CSS surveys showed remarkable consistency, with 13 A/J-derived chromosomes reproducibly conferring resistance to high-fat-diet-induced obesity. Twenty CSS intercrosses, one derived from each of the 19 autosomes and chromosome X, were used to determine the number and location of quantitative trait loci (QTLs) on individual chromosomes and localized six QTLs. However, analyses of mean body weight in intercross progeny versus C57BL/6J provided strong evidence that many QTLs discovered in the CSS surveys eluded detection in these CSS intercrosses. Studies of the temporal effects of these QTLs suggest that obesity resistance was dynamic, with QTLs acting at different ages or after different durations of diet exposure. Thus, these studies provide insight into the genetic architecture of complex traits such as resistance to diet-induced obesity in the C57BL/6J-Chr(A/J)/NaJ CSSs. Because some of the QTLs detected in the CSS intercrosses were not detected using a traditional C57BL/6J x A/J intercross, our results demonstrate that surveys of CSSs and congenic strains derived from them are useful complementary tools for analyzing complex traits.


Alternate JournalMamm. Genome
PubMed ID20127486
PubMed Central IDPMC3831885
Grant ListU54 CA116867 / CA / NCI NIH HHS / United States
P40 RR012305 / RR / NCRR NIH HHS / United States
T32 GM07250-30 / GM / NIGMS NIH HHS / United States
RR12305 / RR / NCRR NIH HHS / United States
R01 DK075040 / DK / NIDDK NIH HHS / United States
U54CA116867 / CA / NCI NIH HHS / United States
T32 GM007250 / GM / NIGMS NIH HHS / United States