Positional Cloning of a Diabetes Gene on Chromosome 11

Baier, Leslie J.

Abstract

We have previously identified a region of linkage to both body mass index (LOD=3.6) and age-adjusted diabetes (LOD=1.7) on chrom 11q23-tel. We are currently confirming and refining the area of linkage by genotyping 10 markers within this region on 3,000 additional individuals. We have also created a physical map by identifying overlapping YAC clones across the region of linkage on chrom 11q. Single nucleotide polymorphisms (SNPs) are being identified on each of the YACs and the SNPs are being genotyped on DNAs from 200 informative sibpairs. SNPs that are associated with either BMI or diabetes are being precisely localized on BAC clones. We are also directly analyzing all known candidate genes in the region, which include the Apo CIII/Apo AIV gene cluster, Apo AI, and the inwardly rectifying potassium channel KCNJ5.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK069072-01
• Application #: 6105977
• Study Section: Special Emphasis Panel (PECR)
• Support Year: 1
• Fiscal Year: 1998

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases
• Country: United States

Publications

Kovacs, Peter; Stumvoll, Michael; Bogardus, Clifton et al. (2006) A functional Tyr1306Cys variant in LARG is associated with increased insulin action in vivo. Diabetes 55:1497-503

Hanson, R L; Looker, H C; Ma, L et al. (2006) Design and analysis of genetic association studies to finely map a locus identified by linkage analysis: sample size and power calculations. Ann Hum Genet 70:332-49

Muller, Yunhua Li; Infante, Aniello M; Hanson, Robert L et al. (2005) Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians. Diabetes 54:3035-9

Baier, Leslie J; Hanson, Robert L (2004) Genetic studies of the etiology of type 2 diabetes in Pima Indians: hunting for pieces to a complicated puzzle. Diabetes 53:1181-6

Baier, Leslie; Kovacs, Peter; Wiedrich, Christopher et al. (2002) Positional cloning of an obesity/diabetes susceptibility gene(s) on chromosome 11 in Pima Indians. Ann N Y Acad Sci 967:258-64

Kovacs, Peter; Yang, Xiaolin; Permana, Paska A et al. (2002) Polymorphisms in the oxygen-regulated protein 150 gene (ORP150) are associated with insulin resistance in Pima Indians. Diabetes 51:1618-21

Jenkinson, C P; Hanson, R; Cray, K et al. (2000) Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians. Int J Obes Relat Metab Disord 24:1233-8