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Research Article Free access | 10.1172/JCI119637

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.

A V Lembertas, L Pérusse, Y C Chagnon, J S Fisler, C H Warden, D A Purcell-Huynh, F T Dionne, J Gagnon, A Nadeau, A J Lusis, and C Bouchard

Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.

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Published September 1, 1997 - More info

Published in Volume 100, Issue 5 on September 1, 1997
J Clin Invest. 1997;100(5):1240–1247. https://doi.org/10.1172/JCI119637.
© 1997 The American Society for Clinical Investigation
Published September 1, 1997 - Version history
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Abstract

Chromosomal synteny between the mouse model and humans was used to map a gene for the complex trait of obesity. Analysis of NZB/BINJ 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 MC3R (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.

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