title: Frequent loss of genome gap region in 4p16.3 subtelomere in early-onset type 2 diabetes mellitus.
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.
authors.affiliation: Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kudo
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Emi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ishigaki
authors.forename: Uiko
authors.initials: U
authors.lastname: Tsunoda
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hinokio
authors.forename: Miho
authors.initials: M
authors.lastname: Ishii
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamada
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D007564:Japan; D008875:Middle Aged; D016615:Telomere / Q000235:genetics*