Gene Expression Profiling On Insulin Resistance And Obesity

我们正在进行全球外显子表达谱分析，以补充正在进行的努力，以确定糖尿病及其预测因子，胰岛素抵抗，胰岛素分泌功能障碍和肥胖的易感基因。为此，我们正在检查外显子表达谱的组织样本，从非糖尿病的全血皮马印第安人使用Affytek外显子arrys查询超过100万个已知的和预测的外显子在整个基因组。 我们收集了225个骨骼肌组织样本和250个脂肪组织样本 来自非糖尿病的皮马印第安人，他们已经使用高胰岛素正葡萄糖钳夹对体内身体组成和胰岛素作用进行了代谢表型分析。大多数这些志愿者的糖尿病状态的随访数据是可用的，长达7-10年后，因此将能够确定该人群中的糖尿病前外显子表达谱。我们已经完成了所有骨骼肌和脂肪组织样本的外显子阵列，目前正在分析这些数据，并与我们使用单核苷酸多态性进行的全基因组关联研究以及外显子组和全基因组测序中收集的许多受试者的基因型数据进行比较。 初步分析已经确定了顺式作用单核苷酸多态性与肌肉和/或脂肪组织中转录本表达水平之间的显著关联。

We are performing global exon expression profiling to complement the ongoing effort to identify susceptibility genes for diabetes and its predictors, insulin resistance, insulin secertory dysfunction and obesity. To this end, we are examining exon expression profiles in tissue samples from non-diabetic full-blooded Pima Indians using Affymetrix exon arrys that query over 1 million known and predicted exons across the entire genome. We have collected 225 skeletal muscle tissue samples and 250 adipose tissue samples from non-diabetic Pima Indians who have been metabolically phenotyped for body composition and insulin action in vivo using the hyperinsulinemic euglycemic clamp. Follow up data is available on the diabtic status of most of these volunteers, up to 7-10 years later, so will be able to identify a prediabtic exon expression profile in this population. We have completed the exon arrays on all skeletal muscle and adipose tissue samples and are currently analyzing these data and comparing to genotypic data collected on many of the subjects from our genome-wide association study using single nucleotide polymorphisms as well as from exome and whole-genome sequencing. Initial analyses have identified signifigant associations between cis-acting sinlge nucleotide polymorphisms and levels of transcript expression in muscle and/or adipose tissue.