An Autosomal Genomic Scan for Loci Linked to Type II Diabetes Mellitus and Body-Mass Index in Pima Indians

Abstract

Genetic factors influence the development of type II diabetes mellitus, but genetic loci for the most common forms of diabetes have not been identified. A genomic scan was conducted to identify loci linked to diabetes and body-mass index (BMI) in Pima Indians, a Native American population with a high prevalence of type II diabetes. Among 264 nuclear families containing 966 siblings, 516 autosomal markers with a median distance between adjacent markers of 6.4 cM were genotyped. Variance-components methods were used to test for linkage with an age-adjusted diabetes score and with BMI. In multipoint analyses, the strongest evidence for linkage with age-adjusted diabetes (LOD = 1.7) was on chromosome 11q, in the region that was also linked most strongly with BMI (LOD = 3.6). Bivariate linkage analyses strongly rejected both the null hypothesis of no linkage with either trait and the null hypothesis of no contribution of the locus to the covariation among the two traits. Sib-pair analyses suggest additional potential diabetes-susceptibility loci on chromosomes 1q and 7q.

Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes

“…This chromosome region encompasses the linkage peak to BMI in Pima Indians [20]. The region contains two inflammation-related genes, THY1 and C1QTNF5, together with a further ten of the most differentially expressed genes.…”

“…These genes are located on chromosome 11q22-q24, which encompasses the linkage peak to BMI in Pima Indians [20]. Quantitative RT-PCR of these genes was carried out using cDNA samples from the subjects used to obtain the microarray data, as differential expression of these genes might be associated with genetic variations of the subjects.…”

“…Quantitative RT-PCR confirmation of the differential expression of positional candidate genes for obesity There were 12 differentially expressed genes that mapped to chromosome 11q22-q24, the region with linkage to BMI in the Pima Indians [20]. Six of these positional candidate Table 1).…”

“…This study was carried out to characterise the most differentially expressed genes in adipocytes from the two subject groups. As a complementary approach to our ongoing positional cloning effort, this study may also help to identify candidate susceptibility genes for obesity on chromosome 11q22-q24, the peak of linkage to obesity in this population [20].…”

Microarray profiling of skeletal muscle tissues from equally obese, non-diabetic insulin-sensitive and insulin-resistant Pima Indians

“…Since insulin resistance is a pre-diabetic phenotype, it is thought that genes influencing this metabolic abnormality could be fewer than those contributing to the complex diabetic syndrome. Chromosomal regions harbouring susceptibility genes for pre-diabetic phenotypes [7] Type II (non-insulin-dependent) diabetes mellitus is an increasingly common metabolic disease involving abnormal regulation of carbohydrate and lipid metab-and diabetes [8] have been identified using linkage analyses in the Pima population.…”