Linkage and linkage disequilibrium mapping of genes influencing human obesity in chromosome region 7q22.1-7q35.
Linkage results suggest that the region of chromosome 7 containing the leptin gene cosegregates with extreme obesity; however, leptin coding region mutations are rare. To investigate whether the leptin flanking sequence and/or a larger 40-cM region (7q22.1-7q35) contributes to obesity, we genotyped individuals from 200 European American families segregating extreme obesity and normal weight (1,020 subjects) using 21 microsatellite markers and two single nucleotide polymorphisms (SNPs) and conducted nonparametric linkage (NPL) analyses. We also carried out transmission disequilibrium tests for 135 European American triads using 27 markers (including eight SNPs). Both quantitative (MERLIN-regress) and qualitative (GENEHUNTER and MERLIN-npl) analyses provided evidence for linkage for BMI (GENEHUNTER NPL = 2.98, 20 cM centromeric to leptin at the marker D7S692; MERLIN Z score = 3.56). Results for several other regions in 7q gave weak linkage. Transmission disequilibrium test (TDT) and quantitative TDT (and quantitative pedigree disequilibrium test) analyses suggest linkage disequilibrium near leptin and other regions of 7q. Our results suggested that there could be two or more genes in chromosome region 7q22.1-7q35 that influence obesity. A new region found by this study (D7S692-D7S523, 7q31.1) has the most consistent linkage results and could harbor obesity-related genes.
Li
Wei-Dong
WD
Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, One Clinical Research Building, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
Li
Ding
D
Wang
Shuang
S
Zhang
Shuanglin
S
Zhao
Hongyu
H
Price
R Arlen
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D020738:Leptin / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D012044:Regression Analysis
D005819:Genetic Markers; D020738:Leptin