Analyses of copy number variation of GK rat reveal new putative type 2 diabetes susceptibility loci.
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.
Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhi-Qiang
ZQ
Ye
Shen
S
Niu
Yang
Y
Yu
Hui
H
Yu
Bao-Hong
BH
Liu
Rong-Xia
RX
Li
Hua-Sheng
HS
Xiao
Rong
R
Zeng
Yi-Xue
YX
Li
Jia-Rui
JR
Wu
Yuan-Yuan
YY
Li
D000818:Animals; D002874:Chromosome Mapping; D055028:Comparative Genomic Hybridization; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D018628:Gene Dosage / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
D035683:MicroRNAs