Identification of the molecular cause of MODY in Japanese by deep sequencing of the regions of the MODY-specific deletion type of Copy Number Variant

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293228
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gifu University
• Principal Investigator: Horikawa Yukio 岐阜大学, 医学部附属病院, 准教授 (10323370)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Jun 岐阜大学, 大学院医学系研究科, 教授 (40270855) ; IIZUKA Katsumi 岐阜大学, 医学部附属病院, 講師 (40431712)
• Co-Investigator(Renkei-kenkyūsha): HOSOMICHI Kazuyoshi 国立遺伝学研究所, 総合遺伝研究系, 助教 (50420948)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 若年糖尿病 MODY / 原因遺伝子 / インスリン分泌不全 / エクソーム / 連鎖解析 / ゲノムコピー数異常 CNV

Outline of Final Research Achievements

We identified the MODY-specific deletion type of CNV in the region without segmental duplication. We next extracted haploinsufficiency genes in the region as MODY candidates and we obtained all candidate variants by sequencing all exons. As a result, it is unlikely that there is a major MODY gene in Japanese, and it is likely that there is a large number of family-specific MODY genes (known as locus heterogeneity). We finally found only one nuclear transcription factor as a convincing new MODY candidate gene by single big family analysis. On the other hand, by small family analysis, we identified two different new MODY candidate genes and push forward the examination of a correlation of the coding protein of the candidate MODY genes with the impaired insulin secretion in the disease.

Free Research Field

糖尿病遺伝素因の同定　インスリン分泌不全発症機序の解明