Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q

Audra V. Lembertas, Louis Pérusse, Yvon C. Chagnon, Janis S. Fisler, Craig H Warden, Deborah A. Purcell-Huynh, France T. Dionne, Jacques Gagnon, André Nadeau, Aldons J. Lusis, Claude Bouchard

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

Abstract

Chromosomal synteny between the mouse model and humans was used to map a gene for the complex trait of obesity. Analysis of NZB/B1NJ x SM/J intercross mice located a quantitative trait locus (QTL) for obesity on distal mouse chromosome 2, in a region syntenic with a large region of human chromosome 20, showing linkage to percent body fat (likelihood of the odds [LOD] score 3.6) and fat mass (LOD score 4.3). The QTL was confirmed in a congenic mouse strain. To test whether the QTL contributes to human obesity, we studied linkage between markers located within a 52-cM region extending from 20p12 to 20q13.3 and measures of obesity in 650 French Canadian subjects from 152 pedigrees participating in the Quebec Family Study. Sib-pair analysis based on a maximum of 258 sib pairs revealed suggestive linkages between the percentage of body fat (P < 0.004), body mass index (P < 0.008), and fasting insulin (P < 0.0005) and a locus extending approximately from ADA (the adenosine deaminase gene) to MCSR (the melanocortin 3 receptor gene). These data provide evidence that a locus on human chromosome 20q contributes to body fat and insulin in a human population, and demonstrate the utility of using interspecies syntenic relationships to find relevant disease loci in humans.

Original languageEnglish (US)
Pages (from-to)1240-1247
Number of pages8
JournalJournal of Clinical Investigation
Volume100
Issue number5
StatePublished - Sep 1 1997

Keywords

  • ADA
  • ASP
  • Body mass index
  • MC3R

ASJC Scopus subject areas

  • Medicine(all)

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