Article

Mammalian Genome

, Volume 15, Issue 6, pp 472-481

First online:

Genetic complexity of an obesity QTL (Fob3) revealedby detailed genetic mapping

  • Ioannis M. StylianouAffiliated withRoslin Institute (Edinburgh)Institute of Cell, Animal and Population Biology, University of Edinburgh
  • , Julian K. ChristiansAffiliated withInstitute of Cell, Animal and Population Biology, University of Edinburgh
  • , Peter D. KeightleyAffiliated withInstitute of Cell, Animal and Population Biology, University of Edinburgh
  • , Lutz BüngerAffiliated withAnimal Breeding & Development, Sustainable Livestock Systems, SAC
  • , Michael ClintonAffiliated withRoslin Institute (Edinburgh)
  • , Grahame BulfieldAffiliated withRoslin Institute (Edinburgh)Institute of Cell, Animal and Population Biology, University of Edinburgh
  • , Simon HorvatAffiliated withRoslin Institute (Edinburgh)Biotechnical Faculty, Zootechnical Department, University of Ljubljana Email author 

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Abstract

Obesity is proving to be a serious health concern in the developed world as well as an unwanted component of growth in livestock production. While recent advances in genetics have identified a number of monogenic causes of obesity, these are responsible for only a small proportion of human cases of obesity. By divergent selection for high and low fat content over 60 generations, we have created Fat (F) and Lean (L) lines of mice that represent a model of polygenic obesity similar to the situation in human populations. From previous crosses of these lines, four body fat quantitative trait loci (QTL) were identified. We have created congenic lines (Fchr15L), by recurrent marker-assisted backcrossing, to introgress the QTL region with the highest LOD score, Fob3 on Chr 15, from the L-Iine into the F-line background. We have further mapped this QTL by progeny testing of recombinants, produced from crosses between the F-line and congenic Fchrl5L mice, showing that the Fob3 QTL region is a composite of at least two smaller effect QTL—the proximal QTL Fob3a is a late-onset obesity QTL, whereas the distal Fob3b is an early-onset obesity QTL.