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.
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.
Lembertas
A V
AV
Department of Medicine, Molecular Biology Institute, University of California, Los Angeles, California 90095-1679, USA.
Pérusse
L
L
Chagnon
Y C
YC
Fisler
J S
JS
Warden
C H
CH
Purcell-Huynh
D A
DA
Dionne
F T
FT
Gagnon
J
J
Nadeau
A
A
Lusis
A J
AJ
Bouchard
C
C
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D051379:Mice; D008814:Mice, Inbred NZB; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*
D007328:Insulin