We are obtaining genome sequence data on 235 Pima Indians, each from a different nuclear family. Among these individuals, 208 had been studied as inpatients in our CRC when they were non-diabetic, and are informative for percent body fat, glucose and insulin responses during a 2hr oral glucose tolerance test, measures of insulin stimulated glucose uptake (clamp), acute insulin response to an intravenous glucose bolus (N=170), and measures of 24hr energy expenditure in a respiratory chamber (N=146). Some had undergone skeletal muscle biopsies (N=83) or subcutaneous abdominal adipose biopsies (N=73). Also among the 235 subjects, 29 individuals had onset age of T2D <25 years, 52 had onset age <30 years, and 31 were non-diabetic as of their last exam at which time they were aged >40 years. Genome sequencing and alignment was outsourced to Complete Genomics Institute (CGI;35 genomes) or Illumina (200 genomes). The data was received from CGI in Oct 2012 and Illumina in March 2013. Genotype calling and variant annotation is being performed in my lab by using GATK (Broad Institute). Association analysis in the 235 samples and in silico prediction programs will be used to prioritize variation for follow-up.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2013
Total Cost
$1,222,486
Indirect Cost
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Muller, Yunhua L; Skelton, Graham; Piaggi, Paolo et al. (2018) Identification and functional analysis of a novel G310D variant in the insulin-like growth factor 1 receptor (IGF1R) gene associated with type 2 diabetes in American Indians. Diabetes Metab Res Rev 34:e2994
Nair, Anup K; Sutherland, Jeff R; Traurig, Michael et al. (2018) Functional and association analysis of an Amerindian-derived population-specific p.(Thr280Met) variant in RBPJL, a component of the PTF1 complex. Eur J Hum Genet 26:238-246
Nair, Anup K; Baier, Leslie J (2018) Using Luciferase Reporter Assays to Identify Functional Variants at Disease-Associated Loci. Methods Mol Biol 1706:303-319
Piaggi, Paolo; Masindova, Ivica; Muller, Yunhua L et al. (2017) A Genome-Wide Association Study Using a Custom Genotyping Array Identifies Variants in GPR158 Associated With Reduced Energy Expenditure in American Indians. Diabetes 66:2284-2295
Hohenadel, M G; Baier, L J; Piaggi, P et al. (2016) The impact of genetic variants on BMI increase during childhood versus adulthood. Int J Obes (Lond) 40:1301-9
Traurig, Michael; Hanson, Robert L; Marinelarena, Alejandra et al. (2016) Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression. Diabetes 65:510-9
Baier, Leslie J; Muller, Yunhua Li; Remedi, Maria Sara et al. (2015) ABCC8 R1420H loss-of-function variant in a Southwest American Indian community: association with increased birth weight and doubled risk of type 2 diabetes. Diabetes :
Nair, Anup K; Baier, Leslie J (2015) Complex Genetics of Type 2 Diabetes and Effect Size: What have We Learned from Isolated Populations? Rev Diabet Stud 12:299-319
Muller, Yunhua L; Hanson, Robert L; Wiessner, Gregory et al. (2015) Assessing FOXO1A as a potential susceptibility locus for type 2 diabetes and obesity in American Indians. Obesity (Silver Spring) 23:1960-5
del Rosario, Melissa C; Ossowski, Vicky; Knowler, William C et al. (2014) Potential epigenetic dysregulation of genes associated with MODY and type 2 diabetes in humans exposed to a diabetic intrauterine environment: an analysis of genome-wide DNA methylation. Metabolism 63:654-60

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