2013 Fiscal Year Final Research Report

Protocol for exome sequencing analysis to identify a causal gene of familial IgA nephropathy

Research Project

Project/Area Number	24710223
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Medical genome science
Research Institution	National Institute of Genetics
Principal Investigator	HOSOMICHI Kazuyoshi 国立遺伝学研究所, 総合遺伝研究系, 助教 (50420948)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	エクソームシーケンス / IgA腎症 / 疾患関連遺伝子
Research Abstract	A genetic predisposition of IgA nephropathy (IgAN) has been suggested by the familial clustering of the disease. To identify the genetic cause of familial IgAN, we applied exome sequencing to a family comprising four biopsy-proven IgAN. Exome sequencing of four affected, two carriers, and two non-affected individuals were captured, followed by Next-generation sequenciing. After several-step filtering including annotation and functional expectation, a novel missense variant F161Y in EEA1 was found to be candidates for familial IgAN. Furthermore, we identified additional 3 rare mutations in 5 affected individuals of 24 familial IgAN probands by exome sequencing. In conclusion, mutations in EEA1 could be causality for 20% of familial IgAN.