Abstract

In a previous genome-wide linkage scan to screen for type 2 diabetes genes in the Pima Indians, the highest LOD score was obtained around marker D1S1677 on chromosome 1q. To further refine this segment carrying the putative diabetes susceptibility locus, we are now evaluating densely spaced single nucleotide polymorphisms (SNPs) by association analysis in selected affected an unaffected subjects. Using mainly the Whitehead Institute Database, we are now focusing on a contig of ~20 yeast artificial chromosomes (YACs) spanning an interval of about 10 cM. We are systematically exploring published as well as novel SNPs, and so far the p-values for association of individual markers range between 0.01 and 0.05. Our current goal is to investigate at least one informative SNP per each YAC, and by performing the association markers as well as their haplotypes, we anticipate that this strategy will result in a defined peak of significant association that will be used to select candidate genes for mutation screening in diabetic subjects.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK069073-01
Application #
6105978
Study Section
Special Emphasis Panel (PECR)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Ma, Lijun; Hanson, Robert L; Que, Lorem N et al. (2007) Variants in ARHGEF11, a Candidate Gene for the Linkage to Type 2 Diabetes Mellitus on Chromosome 1q, Are Nominally Associated With Insulin Resistance and Type 2 Diabetes Mellitus in Pima Indians. Diabetes :
Chu, Winston S; Das, Swapan Kumar; Wang, Hua et al. (2007) Activating transcription factor 6 (ATF6) sequence polymorphisms in type 2 diabetes and pre-diabetic traits. Diabetes 56:856-62
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
Fu, Mao; Sabra, Mona M; Damcott, Coleen et al. (2007) Evidence that Rho guanine nucleotide exchange factor 11 (ARHGEF11) on 1q21 is a type 2 diabetes susceptibility gene in the Old Order Amish. Diabetes 56:1363-8
Zeggini, Eleftheria; Damcott, Coleen M; Hanson, Robert L et al. (2006) Variation within the gene encoding the upstream stimulatory factor 1 does not influence susceptibility to type 2 diabetes in samples from populations with replicated evidence of linkage to chromosome 1q. Diabetes 55:2541-8
Thameem, Farook; Farook, Vidya S; Bogardus, Clifton et al. (2006) Association of amino acid variants in the activating transcription factor 6 gene (ATF6) on 1q21-q23 with type 2 diabetes in Pima Indians. Diabetes 55:839-42
Thameem, Farook; Farook, Vidya S; Yang, Xiaolin et al. (2004) The transcribed endosulfine alpha gene is located within a type 2 diabetes-linked region on 1q: sequence and expression analysis in Pima Indians. Mol Genet Metab 81:16-21
Thameem, Farook; Yang, Xiaolin; Permana, Paska A et al. (2003) Evaluation of the microsomal glutathione S-transferase 3 (MGST3) locus on 1q23 as a Type 2 diabetes susceptibility gene in Pima Indians. Hum Genet 113:353-8
Wolford, J K; Bogardus, C; Ossowski, V et al. (2000) Molecular characterization of the human PEA15 gene on 1q21-q22 and association with type 2 diabetes mellitus in Pima Indians. Gene 241:143-8

Showing the most recent 10 out of 11 publications