Genetic and environmental factors involved in human genomic instability

• Project/Area Number: 25670173
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Human genetics
• Research Institution: National Research Institute for Child Health and Development
• Principal Investigator: FUKAMI maki 独立行政法人国立成育医療研究センター, その他部局等, その他 (40265872)
• Co-Investigator(Kenkyū-buntansha): IGARASHI Maki 独立行政法人国立成育医療研究センター, 分子内分泌研究部, 研究員 (10623035) ; AYABE Tadayuki 独立行政法人国立成育医療研究センター, 分子内分泌研究部, 研究員 (80566555)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 細胞遺伝学 / ゲノム / 染色体微細構造異常 / 疾患 / 遺伝子 / 染色体

Outline of Final Research Achievements

In the present study, we characterized several submicroscopic chromosomal rearrangements that underlie human disorders. We utilized array-based comparative genomic hybridization and multiplex ligation dependent probe amplification. As a result, we identified simple and complex rearrangements underlying aromatase excess syndrome. We also detected a hitherto unreported deletion in the pseudoautosomal region of Y chromosome in a patient with Langer mesomelic dysplasia. In addition, we characterized multiple Y chromosomal rearrangements that are associated with the risk of azo/oligospermia.

Research Products

• [Journal Article] Copy-number variations in Y chromosomal azoospermia factor regions identified by multiplex ligation-dependent probe amplification (2015)
  • Author(s): Saito K, Miyado M, Kobori Y, Tanaka Y, Ishikawa H, Yoshida A, Katsumi M, Saito H, Kubota T, Okada H, Ogata T, Fukami M
  • Journal Title: J Hum Genet Volume: 60(3) Issue: 3 Pages: 127-31
  • DOI: 10.1038/jhg.2014.115
  • Peer Reviewed
• [Journal Article] SOX3 Overdosage Permits Normal Sex Development in Females with Random X Inactivation (2015)
  • Author(s): Igarashi M, Mikami H, Katsumi M, Miyado M, Izumi Y, Ogata T, Fukami M
  • Journal Title: Sex Dev Volume: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Microhomology-Mediated Microduplication in the Y Chromosomal Azoospermia Factor a (AZFa) Region in a Male with Mild Asthenozoospermia. (2015)
  • Author(s): Katsumi M, Ishikawa H, Tanaka Y, Saito K, Kobori Y, Okada H, Saito H, Nakabayashi K, Matsubara Y, Ogata T, Fukami M, Miyado M
  • Journal Title: Cytogenet Genome Res Volume: 3 Issue: 4 Pages: 1-1
  • DOI: 10.1159/000377649
  • Peer Reviewed
• [Journal Article] Genomic basis of aromatase excess syndrome: recombination- and replication-mediated rearrangements leading to CYP19A1 overexpression. (2013)
  • Author(s): Fukami M*, Tsuchiya T, Vollbach H, Brown KA, Abe S, Ohtsu S, Wabitsch M, Gurger H, Sompson ER, Emezawa A, Nakabayashi K, Bulun SE, Shozu M, Ogata T
  • Journal Title: J Clin Endocrinol Metab Volume: 98 Issue: 12 Pages: E2013-E2021
  • DOI: 10.1210/jc.2013-2520
  • Peer Reviewed
• [Journal Article] Cryptic genomic rearrangements in three patients with 46,XY disorders of sex development (2013)
  • Author(s): M. Igarashi, V. C. Dung, E. Suzuki, S. Ida, M. Nakacho, K. Nakabayashi, K. Mizuno, Y. Hayashi, K. Kohri, Y. Kojima, T. Ogata, M. Fukami
  • Journal Title: PLoS. One Volume: 8 Issue: 7 Pages: e68194-e68194
  • DOI: 10.1371/journal.pone.0068194
  • Peer Reviewed
• [Journal Article] Human glutathione S-transferase A (GSTA) family genes are regulated by steroidogenic factor 1 (SF-1) and are involved in steroidogenesis. (2013)
  • Author(s): Matsumura T, Imamichi Y, Mizutani T, Ju Y, Yazawa T, Kawabe S, Kanno M, Ayabe T, Katsumata N, Fukami M, Inatani M, Akagi Y, Umezawa A, Ogata T, Miyamoto K
  • Journal Title: FASEB J Volume: 27 Issue: 8 Pages: 3198-3208
  • DOI: 10.1096/fj.12-222745
  • Peer Reviewed
• [Journal Article] Compound heterozygous deletions in pseudoautosomal region 1 in an infant with mild manifestsations of Langer mesomelic dysplasia. (2013)
  • Author(s): Tsuchiya T, Shibata M, Numabe H, Jinnno T, Nakabayashi K, Nishimura G, Nagai T, Ogata T, Fukami M*
  • Journal Title: Am J Med Genet A Volume: in press Issue: 2 Pages: 505-510
  • DOI: 10.1002/ajmg.a.36284
  • Peer Reviewed
• [Presentation] Molecular diagnosis and management of hereditary gynecomastia. (2013)
  • Author(s): Fukami M
  • Organizer: The 9th Joint meeting of pediatric endocrinology,
  • Place of Presentation: Milan
  • Invited
• [Presentation] 内分泌疾患のゲノムコピー数解析 (2013)
  • Author(s): 深見真紀
  • Organizer: 第86回日本内分泌学会学術総会 シンポジウム
  • Place of Presentation: 仙台
  • Invited
• [Presentation] 新規遺伝子解析技術を用いたヒト性分化疾患・性成熟疾患の病因解析
  • Author(s): 深見真紀
  • Organizer: 日本アンドロロジー学会第32回学術大会.教育講演.
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 小児内分泌疾患の遺伝子解析：新規解析技術を用いた疾患成立機序の解明.
  • Author(s): 深見真紀
  • Organizer: 第22回小児内分泌代謝フォーラムin九州.
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 性分化疾患の遺伝子診断.
  • Author(s): 深見真紀
  • Organizer: 第23回臨床内分泌代謝Update．シンポジウム
  • Place of Presentation: 名古屋
  • Invited
• [Remarks] 国立成育医療研究センター
• [Remarks] 国立成育医療研究センター分子内分泌研究部
  • URL: http://nrichd.ncchd.go.jp/endocrinology/
• [Remarks] 独立行政法人 国立成育医療研究センター 分子内分泌研究部
  • URL: http://nrichd.ncchd.go.jp/endocrinology/