Approach for identification of novel causative genes in male infertility

• Project/Area Number: 26462461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: The University of Tokushima
• Principal Investigator: SATO Youichi 徳島大学, 大学院医歯薬学研究部(薬学系), 准教授 (10363160)
• Co-Investigator(Kenkyū-buntansha): 山内 あい子 徳島大学, 大学院医歯薬学研究部(薬学系), 教授 (30122253) ; 井本 逸勢 (井本 逸勢(橘逸勢)) 徳島大学, 大学院医歯薬学研究部(医学系), 教授 (30258610) ; 岩本 晃明 国際医療福祉大学, 大学病院, 教授 (60046117)
• Co-Investigator(Renkei-kenkyūsha): TAJIMA Atsushi 金沢大学, 医薬保健研究域医学系, 教授 (10396864)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 男性不妊症 / 精子濃度 / 次世代シーケンサー / GWAS / アンドロロジー / 男性不妊

Outline of Final Research Achievements

To identify novel causative genes of male infertility, we searched for genes related to semen parameters using men from the general population and fertile men. And we tried to search for risk loci for azoospermia using azoospermic patients and their families. We identified a locus associated with sperm motility by genome-wide association studies. And we identified candidate genes responsible for the risk of azoospermia using whole-exome sequencing of families. Moreover, we identified several SNPs significantly associated with male infertility.

Research Products

• [Journal Article] An independent validation study of three single nucleotide polymorphisms at the sex hormone-binding globulin locus for testosterone levels identified by genome-wide association studies. (2017)
  • Author(s): Sato Y, Tajima A, Katsurayama M, Nozawa S, Yoshiike M, Koh E, Kanaya J, Namiki M, Matsumiya K, Tsujimura A, Komatsu K, Itoh N, Eguchi J, Imoto I, Yamauchi A, Iwamoto T.
  • Journal Title: Hum Reprod Open Volume: 2017 Issue: 1 Pages: 1-8
  • DOI: 10.1093/hropen/hox002
  • NAID: 120006380963
  • Peer Reviewed / Open Access
• [Journal Article] Anomalous Separation of Small Y-Chromosomal DNA Fragments on Microchip Electrophoresis (2016)
  • Author(s): Mohammad Jabasini, Ashraf Ewis, Youichi Sato, Yutaka Nakahori, Yoshinobu Baba
  • Journal Title: Scientia Pharmaceutica Volume: 84 Pages: 507-513
  • NAID: 120007037472
  • Peer Reviewed
• [Journal Article] A replication study of a candidate locus for follicle-stimulating hormone levels and association analysis for semen quality traits in Japanese men (2016)
  • Author(s): Y.Sato, A.Tajima, M.Katsurayama, S.Nozawa, M.Yoshiike, E.Koh, J.Kanaya, M.Namiki, K.Matsumiya, A.Tsujimura, K.Komatsu, N.Itoh, J.Eguchi, I.Imoto, A.Yamauchi, T.Iwamoto
  • Journal Title: Journal of Human Genetics Volume: 61 Issue: 11 Pages: 911-915
  • DOI: 10.1038/jhg.2016.82
  • Peer Reviewed / Open Access
• [Journal Article] Y chromosome haplogroup D2a1 is significantly associated with high levels of luteinizing hormone in Japanese men (2015)
  • Author(s): Youichi Sato, Toshikatsu Shinka, Shiari Nozawa, Miki Yoshiike, Eitetsue Koh, Jiro Kanaya, Mikio Namiki, Kiyomi Matsumiya, Akira Tsujimura, Kiyoshi Komatsu, Naoki Itoh, Jiro Eguchi, Aiko Yamauchi, Teruaki Iwamoto, Yutaka Nakahori
  • Journal Title: Andrology Volume: in press Issue: 3 Pages: 520-525
  • DOI: 10.1111/andr.12026
  • Peer Reviewed
• [Journal Article] Lack of replication of four candidate SNPs implicated in human male fertility traits: a large-scale population-based study (2015)
  • Author(s): Youichi Sato, Atsushi Tajima, Kouki Tsunematsu, Shiari Nozawa, Miki Yoshiike, Eitetsue Koh, Jiro Kanaya, Mikio Namiki, Kiyomi, Matsumiya, Akira Tsujimura, Kiyoshi Komatsu, Naoki Itoh, Jiro Eguchi, Issei Imoto, Aiko Yamauchi, Teruaki Iwamoto
  • Journal Title: Human Reproduction Volume: in press Issue: 6 Pages: 1505-1509
  • DOI: 10.1093/humrep/dev081
  • NAID: 120005661919
  • Peer Reviewed
• [Journal Article] An association study of four candidate loci for human male fertility traits with male infertility (2015)
  • Author(s): Youichi Sato, Atsushi Tajima, Kouki Tsunematsu, Shiari Nozawa, Miki Yoshiike, Eitetsue Koh, Jiro Kanaya, Mikio Namiki, Kiyomi, Matsumiya, Akira Tsujimura, Kiyoshi Komatsu, Naoki Itoh, Jiro Eguchi, Issei Imoto, Aiko Yamauchi, Teruaki Iwamoto
  • Journal Title: Human Reproduction Volume: in press Issue: 6 Pages: 1510-1514
  • DOI: 10.1093/humrep/dev088
  • NAID: 120005661918
  • Peer Reviewed
• [Journal Article] Y Chromosome gr/gr Subdeletion Is Associated with Lower Semen Quality in Young Men from the General Japanese Population but Not in Fertile Japanese Men (2014)
  • Author(s): Sato Y, Iwamoto T, Shinka T, Nozawa S, Yoshiike M, Koh E, Kanaya J, Namiki M, Matsumiya K, Tsujimura A, Komatsu K, Itoh N, Eguchi J, Yamauchi A, Nakahori Y
  • Journal Title: Biol Reprod Volume: 90(6)(Epub 2014 Apr 23) Issue: 6 Pages: 116-116
  • DOI: 10.1095/biolreprod.114.118810
  • Peer Reviewed
• [Journal Article] Overview of genetic variation in the Y chromosome of modern Japanese males (2014)
  • Author(s): Youichi Sato, Toshikatsu Shinka, Ashraf A. Ewis, Aiko Yamauchi, Teruaki Iwamoto, Yutaka Nakahori
  • Journal Title: Anthropological Science Volume: 122 Issue: 3 Pages: 131-136
  • DOI: 10.1537/ase.140709
  • NAID: 130004694074
  • ISSN: 0918-7960, 1348-8570
  • Peer Reviewed
• [Journal Article] The role of dipeptidyl peptidase 4 (DPP4) in the preservation of renal function: DPP4 involvement in hemoglobin expression (2014)
  • Author(s): Youichi Sato, Takanobu Kamada, Aiko Yamauchi
  • Journal Title: Journal of Endocrinology Volume: 223 Issue: 2 Pages: 133-142
  • DOI: 10.1530/joe-14-0016
  • Peer Reviewed
• [Journal Article] A Meta-analysis of the Association of <i>PPAR</i>γ rs1801282 Polymorphism and NSAID Usage with the Risk of Developing Cancer (2014)
  • Author(s): Mai Nagao, Youichi Sato, Aiko Yamauchi
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 37 Issue: 6 Pages: 1062-1067
  • DOI: 10.1248/bpb.b14-00160
  • NAID: 130004147354
  • ISSN: 0918-6158, 1347-5215
  • Peer Reviewed
• [Journal Article] Development of a fluoride-responsive amide bond cleavage device that is potentially applicable to a traceable linker (2014)
  • Author(s): J. Yamamoto, N. Maeda, C. Komiya, T. Tanaka, M. Denda, K. Ebisuno, W. Nomura, H. Tamamura, Y. Sato, A. Yamauchi, A. Shigenaga, and A. Otaka
  • Journal Title: Tetrahedron Volume: 70 Issue: 34 Pages: 5122-5127
  • DOI: 10.1016/j.tet.2014.05.110
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Development of a traceable linker containing a thiol-responsive amino acid for the enrichment and selective labelling of target proteins (2014)
  • Author(s): J. Yamamoto, M. Denda, N. Maeda, M. Kita, C. Komiya, T. Tanaka, W. Nomura, H. Tamamura, Y. Sato, A. Yamauchi, A. Shigenaga, and A. Otaka
  • Journal Title: Org. Biomol. Chem. Volume: 12 Issue: 23 Pages: 3821-3826
  • DOI: 10.1039/c4ob00622d
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] AZFc部分欠失gr/gr欠失例の臨床像の検討 (2016)
  • Author(s): 内田 将央、佐藤 陽一、古城 公佑、岩本 晃明
  • Organizer: 第61回日本生殖医学会学術講演会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2016-11-03
• [Presentation] Association analyses between copy numbers of genes in the azoospermia factor c (AZFc) region on the Y chromosome and male infertility (2016)
  • Author(s): Imani Soushi, Youichi Sato, Shimozawa Tatsuya, Iwamoto Teruaki and Aiko Yamauchi
  • Organizer: The 13th International Congress of Human genetics
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-06
  • Int'l Joint Research
• [Presentation] A replication study of four candidate loci for sex hormone levels previously identified by genome-wide association studies (2016)
  • Author(s): Youichi Sato, Atsushi Tajima, Katsurayama Motoki, Issei Imoto, Aiko Yamauchi and Iwamoto Teruaki
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-04-05
  • Int'l Joint Research
• [Presentation] A replication study of four candidate loci for sex hormone levels previously identified by genome-wide association studies (2016)
  • Author(s): Youichi Sato, Atsushi Tajima, Katsurayama Motoki, Issei Imoto, Aiko Yamauchi, Iwamoto Teruaki
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Association analyses between copy numbers of genes in the azoospermia factor c (AZFc) region on the Y chromosome and male infertility (2016)
  • Author(s): Imani Soushi, Youichi Sato, Shimozawa Tatsuya, Iwamoto Teruaki, Aiko Yamauchi
  • Organizer: The 13th International Congress of Human Genetics
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] Y染色体上azoospermia factor c (AZFc) 領域内に存在する遺伝子のコピー数と男性不妊症との関連解析 (2015)
  • Author(s): 今仁 聡志，佐藤 陽一，下澤 辰也，岩本 晃明，山内 あい子
  • Organizer: 第38回日本分子生物学年会・第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-02
• [Presentation] 性ホルモン関連遺伝子座3SNPsの日本人男性を対象としたreplication解析 (2015)
  • Author(s): 葛山 元貴，佐藤 陽一，田嶋 敦，井本 逸勢，岩本 晃明，山内 あい子
  • Organizer: 第54回日本薬学会・日本薬剤師会・日本病院薬剤師会中国四国支部学術大会
  • Place of Presentation: 高知市文化プラザかるぽーと（高知県高知市）
  • Year and Date: 2015-10-31
• [Presentation] 男性生殖能力関連候補遺伝子座 4SNPsの日本人男性を対象とした精液パラメータ及び男性不妊症との関連解析 (2014)
  • Author(s): 佐藤 陽一、常松 晃希、田嶋 敦、井本 逸勢、山内 あい子、岩本 晃明
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2014-11-20
• [Presentation] 日本人男性におけるY染色体上DAZ遺伝子の欠失パターンと精液パラメータとの関連解析 (2014)
  • Author(s): 下澤 辰也，佐藤 陽一，岩本 晃明，山内 あい子
  • Organizer: 日本人類遺伝学会第59回大会
  • Place of Presentation: タワーホール船堀（東京都江戸川区）
  • Year and Date: 2014-11-20
• [Remarks] 徳島大学大学院医歯薬学研究部医薬品情報学分野
  • URL: http://www.tokushima-u.ac.jp/ph/faculty/labo/inf/