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Quantitative trait locus analysis for obesity reveals multiple networks of interacting loci

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Abstract

Obesity is a highly heritable and genetically complex trait with hundreds of potential loci identified. An intercross of 513 F2 progeny between the SM/J × NZB/BINJ inbred mouse strains was generated to identify quantitative trait loci (QTL) that are involved in the weight of four fat pads: mesenteric, inguinal, gonadal, and retroperitoneal. Sex and lean body weight were treated as covariates in the analysis of these fat pads. This analysis uncoupled genetic effects related to overall body size from those influencing the adiposity of a mouse. We identified multiple significant QTL. QTL alleles associated with increased lean body weight and individual fat pad weights are contributed by the NZB background. Adiposity loci are distinct from these body size QTLs and high-adiposity alleles are contributed by the SM background. An extended network of epistatic QTL is also observed. A QTL on Chr 19 is the center of a network of eight interacting QTL, Chr 4 is the center of six, and Chr 17 the center of four interacting QTL. We conclude that interacting networks of multiple genes characterize the regulation of fat pad depots and body weight. Haplotype patterns and a literature-driven approach were used to generate hypotheses regarding the identity of the genes and pathways underlying the QTL.

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Acknowledgments

This work was supported by National Institute of Health grants HLB66611 and GM070683 (to GC) and a Jackson Laboratory core grant CA34196. The authors are grateful to Eric Taylor, Colleen Bradstreet, and Tina Tracey for assistance in phenotyping and genotyping, and to Jennifer Torrance for assistance with graphics.

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Correspondence to Gary A. Churchill.

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Stylianou, I.M., Korstanje, R., Li, R. et al. Quantitative trait locus analysis for obesity reveals multiple networks of interacting loci. Mamm Genome 17, 22–36 (2006). https://doi.org/10.1007/s00335-005-0091-2

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  • DOI: https://doi.org/10.1007/s00335-005-0091-2

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