Abstract

Genetic Mapping of Non-Insulin Dependent Diabetes The genetics of non-insulin dependent diabetes mellitus (NIDDM; Type 2 diabetes; adult onset diabetes) will be investigated using linkage analysis with DNA probes revealing restriction fragment length polymorphisms (RFLPs). NIDDM affects 5% of the adult population of the U.S. and complications of the disease make it one of the leading causes of death in this country. NIDDM is familial in mature, and thus is an appropriate subject for genetic investigation. The long term goals are to develop a DNA probe test for the presymptomatic diagnosis of NIDDM and to isolate and characterize the gene(s) which cause NIDDM. We will search for linkage in one large family segregating maturity onset diabetes of the young (MODY) and in the Pima indian tribe which has very high incidence of NIDDM/ RFLP proves to be tested will come from the extensive, well characterized collection at Collaborative Research. By using RFLP probes which are known to be equally spaced along the chromosomes, we can systematically search for linkage. With both 2-point linkage analysis and multilocus linkage analysis we have a high probability of detecting linkage (LOD greater than or equal to 3.0) in each group (MODY family and/or Pima indians) in the first year of screening. The linked probes will be used to test for heterogeneity by analyzing NIDDM families and affected sib-pairs from the general population. With the discovery of linkage, a high resolution genetic map of the NIDDM locus (loci) will we constructed. This will require the isolation of many additional RFLP probes by the use of several directed cloning methods and will narrow the region containing the NIDDM gene to a few million base pairs. Information about the physical structure of the locus will be obtained by hybridizing the linked probes to Southern blots generated by pulse field gel electrophoresis. Under optimum conditions, experiments directed at cloning NIDDM candidate genes will be performed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK041269-04
Application #
3241944
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1989-05-01
Project End
1993-04-30
Budget Start
1991-05-01
Budget End
1993-04-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106

  Publications

Dawson, P A; Mychaleckyj, J C; Fossey, S C et al. (2001) Sequence and functional analysis of GLUT10: a glucose transporter in the Type 2 diabetes-linked region of chromosome 20q12-13.1. Mol Genet Metab 74:186-99
Price, J A; Fossey, S C; Sale, M M et al. (2000) Analysis of the HNF4 alpha gene in Caucasian type II diabetic nephropathic patients. Diabetologia 43:364-72
Fossey, S C; Kuroda, S; Price, J A et al. (2000) Identification and characterization of PRKCBP1, a candidate RACK-like protein. Mamm Genome 11:919-25
Price, J A; Brewer, C S; Howard, T D et al. (1999) A physical map of the 20q12-q13.1 region associated with type 2 diabetes. Genomics 62:208-15
Bowden, D W; Sale, M; Howard, T D et al. (1997) Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy. Diabetes 46:882-6
Howard, T D; Akots, G; Bowden, D W (1996) Physical and genetic mapping of the muscle phosphofructokinase gene (PFKM): reassignment to human chromosome 12q. Genomics 34:122-7
Rothschild, C B; Freedman, B I; Hodge, R et al. (1995) Fructose-1,6-bisphosphatase: genetic and physical mapping to human chromosome 9q22.3 and evaluation in non-insulin-dependent diabetes mellitus. Genomics 29:187-94
Bowden, D W; Krawchuk, M D; Weaver, E J et al. (1995) D20S16 is a complex interspersed repeated sequence: genetic and physical analysis of the locus. Genomics 25:394-403
Rothschild, C B; Akots, G; Hayworth, R et al. (1993) A genetic map of chromosome 20q12-q13.1: multiple highly polymorphic microsatellite and RFLP markers linked to the maturity-onset diabetes of the young (MODY) locus. Am J Hum Genet 52:110-23
Bowden, D W; Akots, G; Rothschild, C B et al. (1992) Linkage analysis of maturity-onset diabetes of the young (MODY): genetic heterogeneity and nonpenetrance. Am J Hum Genet 50:607-18

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