Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Array CGH between GK and Wistar Rats for Detecting Copy Number Variations

ABSTRACT: The Goto-Kakizak (GK) rat, a nonobese animal model of Type 2 diabetes (T2D), were developed by repeated inbreeding of glucose-intolerent individuals selected from Wistar rats. During their development, GK rats suffer from reduced beta-cell mass and insulin resistance spontaneously (T2D phenotype), which are supposed to be caused by loci holding different genotypes between GK and Wistar rats. This array CGH experiment can detect loci which show different copy numbers (genotype) between GK and Wistar rats. These loci serve as a valuable repository for mining candidates contributing to the pathogenesis of T2D. The genomic DNA taken from 3 male GK rats as 3 test samples while pooled genomic DNA from 8 male Wistar rats as the common referrence. For each of the hybridization, a dye-swap was designed as well.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Zhi-Qiang Ye

PROVIDER: E-GEOD-21387 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Ye Zhi-Qiang ZQ Niu Shen S Yu Yang Y Yu Hui H Liu Bao-Hong BH Li Rong-Xia RX Xiao Hua-Sheng HS Zeng Rong R Li Yi-Xue YX Wu Jia-Rui JR Li Yuan-Yuan YY

PloS one 20101123 11

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) c ...[more]

PMID: 21124896

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Project description:There has been an incresing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system we performed microarray-based gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Following pathway analysis and validation of gene lists by RT-PCR, 30 genes from hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase gamma and epsilon, ABCA1, CD47 and the RET protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipidmetabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus sriatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3diabetes. Experiments were performed with 9 animals from each group. Wistar rats (control), streptoztocin-treated Wistar rats (type 1 diabetes) and Goto-Kakizaki rats (type 2 diabetes). The brain was removed and the striatum, hippocampus and prefrontal cortex were dissected. Samples from 3-3 identically treated animals were pooled. That means, 3 biological parallels were prepared from each brain region of type 1 or type 2 diabetic and control animals, amounting to a total of 27 different pooled samples.

Dataset Information

Array CGH between GK and Wistar Rats for Detecting Copy Number Variations

Publications

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

Similar Datasets

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