Non-insulin dependent diabetes mellitus is a common chronic disease that develops in most populations in late middle age. The Pima Indians of Arizona have the highest reported prevalence of this disease in the world and in contrast to many populations the disease often presents at an earlier age. As a result of long-term epidemiological studies in the total population, the familial nature of the disease has been well documented, and segregation analyses suggest the possibility of inheritance by a single additive major gene. This project will search for genetic determinants of NIDDM using the techniques of genetic linkage analysis with genetic markers to identify the chromosomal location of inherited determinants of NIDDM in the Pima Indian population. A number of informative pedigrees have been identified and lymphoblast cell lines from informative members of these pedigrees established. DNA from these lymphoblasts is isolated and polymorphic probes applied to search for evidence of linkage of these markers and NIDDM. Probes with established chromosomal locations will be used to screen the genome to detect genetic linkage with NIDDM as described in Project# Z01 DK 69045-01 (Molecular genetic analysis of a chromosome 4 region harboring agent controlling insulin action). The power to detect linkage was estimated under several sets of assumptions about mode of inheritance of diabetes and informativeness and location of DNA markers. With a large number of sib-pairs and highly polymorphic markers, the power to detect a major diabetes-susceptibility gene in the Pima is high.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
City
State
Country
United States
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Traurig, Michael; Mack, Janel; Hanson, Robert L et al. (2009) Common variation in SIM1 is reproducibly associated with BMI in Pima Indians. Diabetes 58:1682-9
Rong, Rong; Hanson, Robert L; Ortiz, Daniel et al. (2009) Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes 58:478-88
Moore, Allan F; Jablonski, Kathleen A; McAteer, Jarred B et al. (2008) Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes 57:2503-10
Ma, Lijun; Hanson, Robert L; Que, Lorem N et al. (2008) PCLO variants are nominally associated with early-onset type 2 diabetes and insulin resistance in Pima Indians. Diabetes 57:3156-60
Ma, Lijun; Hanson, Robert L; Que, Lorem N et al. (2008) Association analysis of Kruppel-like factor 11 variants with type 2 diabetes in Pima Indians. J Clin Endocrinol Metab 93:3644-9
Franks, P W; Jablonski, K A; Delahanty, L et al. (2007) The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program. Diabetologia 50:2451-60
Muller, Yunhua Li; Hanson, Robert L; Zimmerman, Collin et al. (2007) Variants in the Ca V 2.3 (alpha 1E) subunit of voltage-activated Ca2+ channels are associated with insulin resistance and type 2 diabetes in Pima Indians. Diabetes 56:3089-94
Ma, Lijun; Hanson, Robert L; Que, Lorem N et al. (2007) Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians. Diabetes 56:1454-9
Owen, Katharine R; Groves, Christopher J; Hanson, Robert L et al. (2007) Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects. Diabetes 56:879-83
Saunders, Catherine L; Chiodini, Benedetta D; Sham, Pak et al. (2007) Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity (Silver Spring) 15:2263-75

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