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PMID: 9276742 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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.

The Journal of clinical investigation ·Vol. 100 ·No. 5 ·1997-09-01 ·Pages 1240-7

Lembertas AV, Pérusse L, Chagnon YC, Fisler JS, Warden CH, Purcell-Huynh DA, Dionne FT, Gagnon J, Nadeau A, Lusis AJ, Bouchard C

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.

MeSH Terms
Adipose Tissue/anatomy & histology Adolescent Adult Aged Aged, 80 and over Animals Chromosome Mapping Chromosomes, Human, Pair 20 Female Genetic Linkage Humans Insulin/blood Male Mice Mice, Inbred NZB Middle Aged Obesity/genetics
Chemicals
Insulin
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Lembertas A V
Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.
Pérusse L
Chagnon Y C
Fisler J S
Warden C H
Purcell-Huynh D A
Dionne F T
Gagnon J
Nadeau A
Lusis A J
Bouchard C
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119637
Published
1997-09-01
Pages
1240-7
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508301
Subset
IM
Grants
NCRR NIH HHS · 1P41 RR03655 · United States
NIDDK NIH HHS · DK-45066 · United States
NHLBI NIH HHS · HL-42488 · United States
External Links
PubMed source DOI: 10.1172/JCI119637 PMC Full Text View journal details
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