Integrated genomic and epigenomic analyses to understand the molecular bases for defects in spermatogenesis in humans

• Project/Area Number: 15H04320
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical genome science
• Research Institution: Kanazawa University
• Principal Investigator: Tajima Atsushi 金沢大学, 医学系, 教授 (10396864)
• Co-Investigator(Kenkyū-buntansha): 飯島 将司 金沢大学, 附属病院, 助教 (70749168) ; 並木 幹夫 金沢大学, 医学系, 特任教授 (70155985)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2015: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: 男性不妊症 / ゲノム / エピゲノム / 遺伝リスク

Outline of Final Research Achievements

Integrated genomic and epigenomic analyses including whole-exome sequencing analysis in Japanese patients with idiopathic nonobstructive azoospermia and testicular epigenomic analysis helped us identify candidate “hot spot” genes that harbored various types of mutations (such as genetic and epigenetic mutations). In a two-staged genome-wide association study of sperm motility in Japanese males, furthermore, a single nucleotide polymorphism rs3791686 in ERBB4 on chromosome 2q34 was identified as a novel locus for sperm motility.

Research Products

• [Journal Article] Association of TUSC1 and DPF3 gene polymorphisms with male infertility (2018)
  • Author(s): Sato Youichi、Hasegawa Chise、Tajima Atsushi、Nozawa Shiari、Yoshiike Miki、Koh Eitetsue、Kanaya Jiro、Namiki Mikio、Matsumiya Kiyomi、Tsujimura Akira、Komatsu Kiyoshi、Itoh Naoki、Eguchi Jiro、Yamauchi Aiko、Iwamoto Teruaki
  • Journal Title: Journal of Assisted Reproduction and Genetics Volume: 35 Issue: 2 Pages: 257-263
  • DOI: 10.1007/s10815-017-1052-x
  • NAID: 120006768430
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genome-wide association study identifies ERBB4 on 2q34 as a novel locus associated with sperm motility in Japanese men (2018)
  • Author(s): Sato Y, Tajima A, Sato T, Nozawa S, Yoshiike M, Imoto I, Yamauchi A, Iwamoto T
  • Journal Title: J Med Genet Volume: - Issue: 6 Pages: 415-21
  • DOI: 10.1136/jmedgenet-2017-104991
  • Peer Reviewed / Open Access
• [Journal Article] Prothymosin alpha-deficiency enhances anxiety-like behaviors and impairs learning/memory-functions and neurogenesis (2017)
  • Author(s): Ueda H, Sasaki K, Halder SK, Deguchi Y, Takao K, Miyakawa T, Tajima A
  • Journal Title: Journal of Neurochemistry Volume: 141 Issue: 1 Pages: 124-136
  • DOI: 10.1111/jnc.13963
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Association of common polymorphisms with gestational diabetes mellitus in Japanese women: A case-control study (2017)
  • Author(s): Kasuga, Y. Hata, K. Tajima, A. Ochiai, D. Saisho, Y. Matsumoto, T. Arata, N. Miyakoshi, K. Tanaka, M.
  • Journal Title: Endocrine Journal Volume: 64 Issue: 4 Pages: 463-475
  • DOI: 10.1507/endocrj.EJ16-0431
  • NAID: 130005630406
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity (2017)
  • Author(s): Nishi Akira、Numata Shusuke、Tajima Atsushi、Zhu Xiaolei、Ito Koki、Saito Atsushi、Kato Yusuke、Kinoshita Makoto、Shimodera Shinji、Ono Shinji、Ochi Shinichiro、Imamura Akira、Kurotaki Naohiro、Ueno Shu-ichi、Iwata Nakao、Fukui Kiyoshi、Imoto Issei、Kamiya Atsushi、Ohmori Tetsuro
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 2887-2887
  • DOI: 10.1038/s41598-017-02792-z
  • NAID: 120006309984
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals (2017)
  • Author(s): Shinmyo Yohei、Terashita Yukari、Dinh Duong Tung Anh、Horiike Toshihide、Kawasumi Muneo、Hosomichi Kazuyoshi、Tajima Atsushi、Kawasaki Hiroshi
  • Journal Title: Cell Rep Volume: 20 Issue: 9 Pages: 2131-2143
  • DOI: 10.1016/j.celrep.2017.08.024
  • NAID: 120006374153
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Whole-exome sequencing analysis of supernumerary teeth occurrence in Japanese individuals (2017)
  • Author(s): Takahashi M, Hosomichi K, Yamaguchi T, Yano K, Funatsu T, Adel M, Haga S, Maki K, Tajima A
  • Journal Title: Hum Genome Variation Volume: 印刷中 Issue: 1 Pages: 16046-16046
  • DOI: 10.1038/hgv.2016.46
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan. (2017)
  • Author(s): Kanzawa-Kiriyama H, Kryukov K, Jinam TA, Hosomichi K, Saso A, Suwa G, Ueda S, Yoneda M, Tajima A, Shinoda KI, Inoue I, Saitou N. A partial nuclear genome of the Jomons who lived 3000 years ago in Fukushima, Japan
  • Journal Title: J Hum Genetics Volume: 印刷中 Issue: 2 Pages: 213-221
  • DOI: 10.1038/jhg.2016.110
  • NAID: 40021064864
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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] A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability. (2016)
  • Author(s): Kawarai T, Tajima A, Kuroda Y, Saji N, Orlacchio A, Terasawa H, Shimizu H, Kita Y, Izumi Y, Mitsui T, Imoto I, Kaji R.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 87 Issue: 6 Pages: 656-662
  • DOI: 10.1136/jnnp-2014-309828
  • 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] A de novo mutation of the LDL receptor gene as the cause of familial hypercholesterolemia identified using whole exome sequencing. (2016)
  • Author(s): Tada H, Hosomichi K, Okada H, Kawashiri MA, Nohara A, Inazu A, Tomizawa S, Tajima A, Mabuchi H, Hayashi K.
  • Journal Title: Clin Chim Acta. Volume: 453 Pages: 194-196
  • DOI: 10.1016/j.cca.2015.12.028
  • Peer Reviewed / Open Access
• [Journal Article] CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation (2016)
  • Author(s): Shinmyo Y., Tanaka S., Tsunoda S., Hosomichi K., Tajima A. and Kawasaki H.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 20611-20611
  • DOI: 10.1038/srep20611
  • NAID: 120005764199
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] Sex differences of leukocytes DNA methylation adjusted for estimated cellular proportions. (2015)
  • Author(s): Inoshita M, Numata S, Tajima A, Kinoshita M, Umehara H, Yamamori H, Hashimoto R, Imoto I, Ohmori T.
  • Journal Title: Biol Sex Differ. Volume: 6 Issue: 1 Pages: 11-11
  • DOI: 10.1186/s13293-015-0029-7
  • NAID: 120005646687
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The impact of next-generation sequencing technologies on HLA research. (2015)
  • Author(s): Hosomichi K, Shiina T, Tajima A, Inoue I.
  • Journal Title: Journal of human genetics Volume: 60 Issue: 11 Pages: 665-673
  • DOI: 10.1038/jhg.2015.102
  • NAID: 40020655134
  • Peer Reviewed / Open Access
• [Presentation] Sequence Capture法によるKIRハプロタイプ構造決定と日本人におけるその多様性 (2017)
  • Author(s): 細道一善、井ノ上逸朗、田嶋敦、中岡博史、椎名隆、東史啓、猪子英俊、屋部登志雄、森島泰雄
  • Organizer: 第26回日本組織適合性学会大会
• [Presentation] 古代ゲノム解析から推定される北アジアの人類集団史 (2017)
  • Author(s): 佐藤丈寛、安達登、木村亮介、米田穣、太田博樹、田嶋敦、豊田敦、松前ひろみ、小金渕佳江、清水健太郎、埴原恒彦、Andrzej Weber、加藤博文、石田肇
  • Organizer: 日本人類遺伝学会第62回大会
• [Presentation] GWASによる精子濃度の関連遺伝子座の探索 (2017)
  • Author(s): 木口美沙妃、佐藤陽一、田嶋敦、佐藤丈寛、井本逸勢、岩本晃明、山内あい子
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）
• [Presentation] GWASによる血中inhibin Bレベル関連遺伝子座の探索 (2017)
  • Author(s): 小薬鈴、佐藤陽一、田嶋敦、佐藤丈寛、井本逸勢、岩本晃明、山内あい子
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）
• [Presentation] 北海道礼文島浜中２遺跡出土オホーツク文化期人骨のゲノム解析． (2016)
  • Author(s): 佐藤丈寛、安達登、木村亮介、米田穣、太田博樹、田嶋敦、松前ひろみ、清水健太郎、Andrzej Weber、加藤博文、石田肇．
  • Organizer: 第70回日本人類学会大会
  • Place of Presentation: NSG学生総合プラザSTEP（新潟）
  • Year and Date: 2016-10-08
• [Presentation] 次世代シークエンサーを用いた未診断疾患への取り組み． (2016)
  • Author(s): 田嶋敦．
  • Organizer: 第70回日本小児神経学会北陸地方会公開シンポジウム
  • Place of Presentation: 金沢大学附属病院 宝ホール（金沢）
  • Year and Date: 2016-09-04
  • Invited
• [Presentation] A replication study of four candidate loci for sex hormone levels, identified by genome-wide association studies. (2016)
  • Author(s): Sato Y, Tajima A, Katsurayama M, Imoto I, Yamauchi A, Iwamoto T.
  • Organizer: ICHG2016（第13回国際人類遺伝学会）
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] High-throughput sequencing method of the KIR haplotype for integrated MHC-KIR genotyping approach for clinical applications. (2016)
  • Author(s): Hosomichi K, Yabe T, Shiina T, Tajima A, Inoue I.
  • Organizer: ICHG2016（第13回国際人類遺伝学会）
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-04-03
  • Int'l Joint Research
• [Presentation] 性ホルモン関連遺伝子座3 SNPs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）
  • Year and Date: 2015-10-31
• [Presentation] 細胞異種性を考慮した末梢血白血球のDNAメチル化の性差の検討． (2015)
  • Author(s): 井下真利、沼田周助、田嶋敦、木下誠、梅原英裕、山森英長、橋本亮太、井本逸勢、大森哲郎．
  • Organizer: 第45回日本神経精神薬理学会・第37回日本生物学的精神医学会 合同年会
  • Place of Presentation: タワーホール船堀（東京）
  • Year and Date: 2015-09-24
• [Remarks] 金沢大学医薬保健研究域医学系 革新ゲノム情報学分野
  • URL: http://big.w3.kanazawa-u.ac.jp
• [Remarks] 金沢大学 医薬保健研究域医学系 革新ゲノム情報学分野
  • URL: http://big.w3.kanazawa-u.ac.jp