Identification of causative genetic locus of a large family with hearing loss

• Project/Area Number: 25462637
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Chiba University (2015); Kyoto University (2013)
• Principal Investigator: Sekine Akihiro 千葉大学, 予防医学センター, 教授 (30425631)
• Co-Investigator(Kenkyū-buntansha): OKANO Takayuki 京都大学, 医学部附属病院, 助教 (60642931)
• Co-Investigator(Renkei-kenkyūsha): KITAJIRI Shinichiro 京都大学, 医学部附属病院, 助教 (00532970) ; YAMAMOTO Norio 京都大学, 医学部附属病院, 助教 (70378644) ; TAKEMURA Ryo 千葉大学, 医学部附属病院, 特任助教 (50747516) ; KITAHARA Terue 千葉大学, 予防医学センター, 特任研究員 (70761162) ; MASHIMO Yoichi 千葉大学, 大学院医学研究院, 技術職員 (90422253)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed(Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost : ¥4,000,000、Indirect Cost : ¥1,200,000); Fiscal Year 2015 : ¥650,000 (Direct Cost : ¥500,000、Indirect Cost : ¥150,000); Fiscal Year 2014 : ¥1,170,000 (Direct Cost : ¥900,000、Indirect Cost : ¥270,000); Fiscal Year 2013 : ¥3,380,000 (Direct Cost : ¥2,600,000、Indirect Cost : ¥780,000)
• Keywords: 遺伝性難聴 / パラメトリック連鎖解析 / 大家系 / 全ゲノム解析 / 原因未知 / 難聴 / 原因遺伝子 / ゲノム解析 / パラメトリック解析

Outline of Final Research Achievements

To identify the causative genetic loci in a large family (affected:12, unaffected:24) with hereditary hearing loss, we performed a parametric linkage analysis using variations detected by whole genome sequencing (HiSeq) and genome wide association study (affected vs unaffected individuals) by human Omni2.5M+exon array. Highest LOD score (2.01~2.71) by parametric linkage mapping was observed a 79kb region in chr13p. Also, 79Mb (p value~1x10-6, odds ratio~14.4) in chr13p included the preceding 79kb was indicated the sole candidate region by genome wide association study. Therefore, sequencing of target 79kb region by PacBioRSII, and succeeded in narrowing the 4 loci included a causative locus exhibiting mutually high linkage disequilibrium.

Research Products

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• [Journal Article] MMP20 and ARMS2/HTRA1 are Associated with Neovascular Lesion Size in Age-Related Macular Degeneration (2015)
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• [Journal Article] Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia. (2015)
  • Author(s): Miyake M, Yamashiro K, Tabara Y, Suda K, Morooka S, Nakanishi H, Khor CC, Chen P, Qiao F, Nakata I, Akagi-Kurashige Y, Gotoh N, Tsujikawa A, Meguro A, Kusuhara S, Polasek O, Hayward C, Wright AF, Campbell H, Mizuki N, et al
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• [Journal Article] Calcium, ARMS2 Genotype, and Chlamydia Pneumoniae Infection in Early Age-Related Macular Degeneration: a Multivariate Analysis from the Nagahama Study. (2015)
  • Author(s): Nakata I, Yamashiro K, Kawaguchi T, Nakanishi H, Akagi-Kurashige Y, Miyake M, Tsujikawa A, Yamada R, Matsuda F, Yoshimura N; Nagahama Study Group.
  • Journal Title: Sci Rep. Volume : 5 Pages : 9345-9345
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• [Journal Article] Tooth loss and atherosclerosis: The Nagahama study (2015)
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• [Journal Article] Knee pain and low back pain additively disturb sleep in the general population: A cross-sectional analysis of the nagahama study (2015)
  • Journal Title: PLOS ONE Volume : 10 Issue : 10
  • Publisher: Public Library of Science
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  • Journal Title: Nature Communications Volume : 6 Pages : 7754-7754
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• [Journal Article] Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study. (2015)
  • Journal Title: Journal of autoimmunity Volume : 59 Pages : 85-90
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  • Year and Date: 2015-03-26
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• [Journal Article] Central blood pressure relates more strongly to retinal arteriolar narrowing than brachial blood pressure: The Nagahama Study (2015)
  • Volume: 33
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  • Publisher: Kyoto University
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  • Author(s): Tabara Y., Muro S., Takahashi Y., Setoh K., Kawaguchi T., Terao C., Kosugi S., Sekine A., Yamada R., Nakayama T., Mishima M., Matsuda F. : Nagahama Study Group.
  • Journal Title: Atherosclerosis Volume : 232 Pages : 59-64
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• [Journal Article] Association between the cholesteryl ester transfer protein gene and polypoidal choroidal vasculopathy. (2013)
  • Author(s): Nakata I., Yamashiro K., Kawaguchi T., Gotoh N., Nakanishi H., Akagi-Kurashige Y., Miyake M., Tsujikawa A., Oishi A., Saito M., Iida T., Yamada R., Matsuda F., Yoshimura N..; Nagahama Study Group.
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• [Journal Article] Prevalence and characteristics of age-related macular degeneration in the Japanese population: the Nagahama study. (2013)
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• [Journal Article] Mastication and risk for diabetes in a Japanese population: a cross-sectional study. (2013)
  • Author(s): Yamazaki T., Yamori M., Asai K., Nakano-Araki I., Yamaguchi A., Takahashi K., Sekine A., Matsuda F., Kosugi S., Nakayama T., Inagaki N., Bessho K.; Nagahama Study Collaboration Group.
  • Journal Title: PLoS One. Volume : 8
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• [Journal Article] Association of Longer QT Interval With Arterial Waveform and Lower Pulse Pressure Amplification: The Nagahama Study. (2013)
  • Author(s): Tabara Y., Takahashi Y., Kohara K., Setoh K., Kawaguchi T., Terao C., Igase M., Yamada R., Kosugi S., Sekine A., Miki T., Nakayama T., Matsuda F.; Nagahama Study Group.
  • Journal Title: Am. J. Hypertens. Volume : 26 Pages : 973-980
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• [Journal Article] Increased aortic wave reflection and smaller pulse pressure amplification in smokers and passive smokers confirmed by urinary cotinine levels: The Nagahama Study. (2013)
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  • Journal Title: Int. J. Cardiol. Volume : 168 Pages : 2673-2677
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• [Journal Article] Prevalence of postmicturition urinary incontinence in Japanese men: Comparison with other types of incontinence. (2013)
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• [Journal Article] NUDT3 rs206936 is associated with body mass index in obese Japanese women. (2013)
  • Author(s): Kitamoto A. et al.
  • Journal Title: Endocr. J. Volume : 60 Pages : 991-1000
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• [Journal Article] Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan. (2013)
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  • Journal Title: Hum. Genet. Volume : 132 Pages : 783-792
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• [Journal Article] Replication study of 15 recently published Loci for body fat distribution in the Japanese population. (2013)
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  • Journal Title: J. Atheroscler. Thromb. Volume : 20 Pages : 336-350
  • Peer Reviewed
• [Presentation] 特別講演１：弾性線維腫の大家系パラメトリック連鎖解析による原因遺伝子の探索 (2016)
  • Author(s): 関根章博、竹村亮、真下陽一、北原輝栄、藤原作平
  • Organizer: 第98回日本皮膚科学会大分地方会
  • Place of Presentation: 大分県労働福祉会館ソレイユ（大分県・大分市）
  • Year and Date: 2016-03-05
  • Invited
• [Presentation] ショートリードを用いたWhole Genome Sequenceで得られた変異に対する評価. (2015)
  • Author(s): 竹村亮, 北原輝栄, 関根章博
  • Organizer: 日本人類遺伝学会第60回大会
  • Place of Presentation: 京王プラザホテル（東京都・新宿）
  • Year and Date: 2015-10-16
• [Presentation] 遺伝カウンセリングに必要な全ゲノム解析情報の精度と検証 (2015)
  • Author(s): 関根章博、竹村亮、真下陽一、北原輝栄、山下泰生、羽田明
  • Organizer: 第39回日本遺伝カウンセリング学会各術集会
  • Place of Presentation: 三井ガーデンホテル千葉（千葉県・千葉市）
  • Year and Date: 2015-06-26
  • Invited
• [Presentation] 先天性難聴の遺伝学的検査における症例調査 (2013)
  • Author(s): 中國正祥、北尻真一郎、谷口美玲、岡野高之、村上裕美、関根章博、柴田有花、土屋 未央、小杉 眞司
  • Organizer: 日本人類遺伝学会第58回大会
  • Place of Presentation: 宮城県仙台
• [Presentation] 医薬品副作用情報データベースを用いた横紋筋融解症の要因検討 (2013)
  • Author(s): 中國正祥、関根章博、水澤精穂、寺西啓、柴田有花、土屋実央、小杉眞司
  • Organizer: 第37回日本遺伝カウンセリング学会
  • Place of Presentation: 神奈川県川崎
• [Presentation] Establishment of an accurate genome sequencing method combining next generation short-read (Hisq, Miseq) and long-read (PacBio) sequencers (2013)
  • Author(s): sekine A.
  • Organizer: Ｏｋｉｎａｗａ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｐｒｏｊｙｅｃｔ ｆｏｒ Ｃｏｎｓｔｒｕｃｔｉｏｎ ｏｆ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｃｌｕｓｔｅｒ ａｎｄ Ｉｎｄｕｓｔｒｙ ｂａｓｅｄ on Advanced Genomic Research.
  • Place of Presentation: okinawa naha
  • Invited
• [Book] 最新内分泌代謝学「内分泌代謝疾患のゲノム、エピゲノム解析」 (2013)
  • Author(s): 関根章博（監修：中尾一和）
  • Publisher: 診断と治療社
• [Remarks] 千葉大学予防医学センター