Identification of autosomal recessive deafness causing gene mapped on chromosome7 by the whole genome linkage analysis

• Project/Area Number: 21791645
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: Keio University
• Principal Investigator: KOJIMA Sabinekazuko 慶應義塾大学, 医学部, 助教 (10445439)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 非症候群性難聴 / 家族性難聴 / 連鎖解析 / 変異探索 / 非症候群性

Research Abstract

I have mapped an autosmal-recessive nonsyndromic deafness locus(DFNB78) to an 8. 7-Mb interval on human chromosome 7q21. 11-q21. 13 by whole genome linkage analysis of a large Turkish family. Furthermore, I have narrowed down the DFNB78 locus by the homozygosity mapping using SNPs in the candidate region. During I was performing mutation search on the 11 candidate genes, it was reported that the cause of DFNB39 which was previously mapped in 18-Mb region on 7q11. 22-q21. 12 by the linkage analysis of the Pakistani family is the mutation of non-coding region in a hepatocyte growth factor(HGF) gene. In the DFNB78 family, I found exactly the same 3-bases deletion in intron4(c. 482+1986_1988delTGA) of HGF gene. I considered this mutation a common founder mutation in South Asia and the Near and Middle East.