We are continuing our total genome scan on 2502 Finnish individuals, including 532 families with at least 2 affected sibs, at a 10cM resolution to find the susceptibility genes for type II diabetes mellitus. We have completed over 300,000 post-processed genotypes and finished scanning chromosomes 1, 2, 7, 8, 15 and 16. Our throughput has doubled over the last year to an average of 12,000 per week. Our average error rate is in the region of 0.3%. Using multi-point linkage analysis with affected sib-pairs we have been able to exclude the D2S125 region at the telomeric portion of 2q at a lambdas value of 1.35 or more. This locus was linked to NIDDM in a sample of Mexican-Americans and has an estimated lambdas value of 1.37 (NIDDM1) under an additive model. Furthermore, we are looking at the 12q region for the NIDDM2 locus which showed significant linkage in a population from the Botnia region of Finland. At present we are working towards doubling our throughput by introducing multiplex PCR and using gels with increased lanes. In addition we are designing a database system in SYBASE to handle the 2500 extra samples which will arrive during the course of the next year. The latter samples will help us in fine mapping.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG000024-02
Application #
2576530
Study Section
Special Emphasis Panel (LGT)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
1996
Total Cost
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Teslovich, Tanya M; Kim, Daniel Seung; Yin, Xianyong et al. (2018) Identification of seven novel loci associated with amino acid levels using single-variant and gene-based tests in 8545 Finnish men from the METSIM study. Hum Mol Genet 27:1664-1674
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Latva-Rasku, Aino; Honka, Miikka-Juhani; Stan?áková, Alena et al. (2018) A Partial Loss-of-Function Variant in AKT2 Is Associated With Reduced Insulin-Mediated Glucose Uptake in Multiple Insulin-Sensitive Tissues: A Genotype-Based Callback Positron Emission Tomography Study. Diabetes 67:334-342
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Wood, Andrew R; Jonsson, Anna; Jackson, Anne U et al. (2017) A Genome-Wide Association Study of IVGTT-Based Measures of First-Phase Insulin Secretion Refines the Underlying Physiology of Type 2 Diabetes Variants. Diabetes 66:2296-2309
Manning, Alisa (see original citation for additional authors) (2017) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes 66:2019-2032
Roman, Tamara S; Cannon, Maren E; Vadlamudi, Swarooparani et al. (2017) A Type 2 Diabetes-Associated Functional Regulatory Variant in a Pancreatic Islet Enhancer at the ADCY5 Locus. Diabetes 66:2521-2530
Surendran, Praveen (see original citation for additional authors) (2016) Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat Genet 48:1151-1161
Rodríguez, Alejandra; Gonzalez, Luis; Ko, Arthur et al. (2016) Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene. Arterioscler Thromb Vasc Biol 36:1350-5
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