Abstract
Previous studies on the LG,SM advanced intercross line have identified approximately 40 quantitative trait loci (QTL) for long -bone (humerus, ulna, femur, and tibia) lengths. In this study, long-bone-length QTL were fine-mapped in the F34 generation (n = 1424) of the LG,SM advanced intercross. Environmental effects were assessed by dividing the population by sex between high-fat and low-fat diets, producing eight sex/diet cohorts. We identified 145 individual bone-length QTL comprising 45 pleiotropic QTL; 69 replicated QTL from previous studies, 35 were new traits significant at previously identified loci, and 41 were novel QTL. Many QTL affected only a subset of the population based on sex and/or diet. Eight of ten known skeletal growth genes were upregulated in 3-week-old LG/J male proximal tibial growth plates relative to SM/J.The sequences of parental strains LG/J and SM/J indicated the presence of over half a million polymorphisms in the confidence intervals of these 45 QTL. We examined 526 polymorphisms and found that 97 represented radical changes to amino acid composition while 40 were predicted to be deleterious to protein function.Additional experimentation is required to understand how changes in gene regulation or protein function can alter the genetic architecture and interact with the environment to produce phenotypic variation.
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Acknowledgments
The authors gratefully acknowledge the support of National Institutes of Health grant AR053224. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is funded through a federal contract from the National Institutes of Health to The Johns Hopkins University(contract number HHSN268200782096C). EAN was supported by a Ford Foundation Diversity Dissertation Grant and a Monticello College Foundation Olin Fellowship for Women.
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Norgard, E.A., Lawson, H.A., Pletscher, L.S. et al. Genetic factors and diet affect long-bone length in the F34 LG,SM advanced intercross. Mamm Genome 22, 178–196 (2011). https://doi.org/10.1007/s00335-010-9311-5
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DOI: https://doi.org/10.1007/s00335-010-9311-5