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Experimental Diabetes Research
Volume 2011, Article ID 498460, 10 pages
http://dx.doi.org/10.1155/2011/498460
Research Article

Frequent Loss of Genome Gap Region in 4p16.3 Subtelomere in Early-Onset Type 2 Diabetes Mellitus

1Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan
2CNV Laboratory, DNA Chip Research Institute, 1-1-43 Suehiro-cho, Tsurumi-ku Yokohama, Kanagawa 230-0045, Japan
3Department of Metabolic Diseases, Center for Metabolic Diseases, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan

Received 6 October 2010; Revised 21 February 2011; Accepted 30 March 2011

Academic Editor: Kazuya Yamagata

Copyright © 2011 Hirohito Kudo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A small portion of Type 2 diabetes mellitus (T2DM) is familial, but the majority occurs as sporadic disease. Although causative genes are found in some rare forms, the genetic basis for sporadic T2DM is largely unknown. We searched for a copy number abnormality in 100 early-onset Japanese T2DM patients (onset age <35 years) by whole-genome screening with a copy number variation BeadChip. Within the 1.3-Mb subtelomeric region on chromosome 4p16.3, we found copy number losses in early-onset T2DM (13 of 100 T2DM versus one of 100 controls). This region surrounds a genome gap, which is rich in multiple low copy repeats. Subsequent region-targeted high-density custom-made oligonucleotide microarray experiments verified the copy number losses and delineated structural changes in the 1.3-Mb region. The results suggested that copy number losses of the genes in the deleted region around the genome gap in 4p16.3 may play significant roles in the etiology of T2DM.