Analyses of copy number variation of GK rat reveal new putative type 2 diabetes susceptibility loci.

Abstract

Large efforts have been taken to search for genes responsible for type 2 diabetes (T2D), but have resulted in only about 20 in humans due to its complexity and heterogeneity. The GK rat, a spontanous T2D model, offers us a superior opportunity to search for more diabetic genes. Utilizing array comparative genome hybridization (aCGH) technology, we identifed 137 non-redundant copy number variation (CNV) regions from the GK rats when using normal Wistar rats as control. These CNV regions (CNVRs) covered approximately 36 Mb nucleotides, accounting for about 1% of the whole genome. By integrating information from gene annotations and disease knowledge, we investigated the CNVRs comprehensively for mining new T2D genes. As a result, we prioritized 16 putative protein-coding genes and two microRNA genes (rno-mir-30b and rno-mir-30d) as good candidates. The catalogue of CNVRs between GK and Wistar rats identified in this work served as a repository for mining genes that might play roles in the pathogenesis of T2D. Moreover, our efforts in utilizing bioinformatics methods to prioritize good candidate genes provided a more specific set of putative candidates. These findings would contribute to the research into the genetic basis of T2D, and thus shed light on its pathogenesis.