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analyses of copy number variation of gk rat reveal new putative type 2 diabetes susceptibility loci拷贝数变异的分析gk大鼠揭示新的假定的2型糖尿病易感性位点
Analyses of Copy Number Variation of GK Rat Reveal
New Putative Type 2 Diabetes Susceptibility Loci
1,2 1 1 1,2 2 1 1
Zhi-Qiang Ye , Shen Niu , Yang Yu , Hui Yu , Bao-Hong Liu , Rong-Xia Li , Hua-Sheng Xiao , Rong
1 1,2 1 1,2
Zeng , Yi-Xue Li , Jia-Rui Wu *, Yuan-Yuan Li *
1 Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China, 2 Shanghai Center for Bioinformation
Technology, Shanghai, China
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.
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