A balanced chromosomal translocation affects the inner nucleus positioning of thederivative chromosomes or not.

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 18590311
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Shinshu University
• Principal Investigator: WAKUI Keiko Shinshu University, Medical Genetics, Assistant Professor (50324249)
• Co-Investigator(Kenkyū-buntansha): FUKUSHIMA Yoshimitsu Shinshu University, Medical Genetics, Professor (70273084)
• Project Period (FY): 2006 – 2007
• Keywords: structural chromosomal abnormality / 3D-FISH analysis / gene / genome / position effects

Research Abstract

In the case of a patient with a disease associated balanced chromosomal rearrangements (DBCRs), one of the gene that disrupted by chromosomal rearrangements is possible to be confirmed as a responsible gene of the disease. If there were no known genes at the breakpoints, we have considered that the clinical features of the patient were not related to the chromosomal rearrangements. But, we speculated that it is possible that chromosomal rearrangements lead to change the inner nucleus spatial organization of the genome, and the breakpoint site affects the disease causing gene in such DBCRs patients. We analyzed a case of a balanced translocation: t(11; 22) (q23; q11) by FISH on three-dimensionally preserved cells (3D FISH) using several BAC clones, which were closely mapped the breakpoints. We devised a new design of the combination of the probes which can be recognized four different targeted chromosomes each other in a 3D preserved nucleus. We verified that newly-devised probe design is effective for this research. And, we established a protocol using direct-labeled FISH method instead of using previous time-consuming indirect-labeled method. We reviewed the appropriate images for this research, and we improved how to obtain the ideal images of the nucleus, how to operate 3D computer software, etc. Although, we could not finish 3D FISH analysis for many patients with DBCRs, and could not show by means of evidence of our hypothesis in two years, we established new strategy to detect four kinds of chromosomes involving translocation in a 3D preserved nucleus for our research purpose. These are the important products to propose the new mechanism of DBCRs and position effects.

Research Products

• [Journal Article] De-novo balanced translocation between 7q31 and 10p14 ina girl with central precocious puberty, moderate mental retardation, and severe speech impairment. (2008)
  • Author(s): Kosho T, Sakazume S, Kawame H, Wakui K, Wada T, Okoshi Y, Mikawa M, Hasegawa T, Matsuura N, Niikawa N, Matsumoto N, Fukushima Y.
  • Journal Title: Clin Dysmorphol 17 Pages: 31-34
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] De-novo balanced translocation between 7q31 and 10p14 in a girl with central precocious puberty, moderate mental retardation, and severe speech impairment (2008)
  • Author(s): Kosho, T., Sakazume, S., Kawame, H., Wakui, K., Wada, T., Okoshi, Y., Mikawa, M., Hasegawa, T., Matsuura, N., Niikawa, N., Matsumoto, N., Fukushima, Y
  • Journal Title: Clin Dysmorphol 17 Pages: 31-34
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A complex karyotype, including a three-way translocation generating a NUP98-HOXD13 transcript, in an infant with acute myeloid leukemia. (2007)
  • Author(s): Hidaka E, Tanaka M, Matsuda K, Ishikawa-Matsumura M, Yamauchi K, Sano K, Honda T, Wakui K, Yanagisawa R, Nakazawa Y, Sakashita K, Shiohara M, Ishii E, Koike K.
  • Journal Title: Cancer Genet Cytogenet 176 Pages: 137-413
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A genomewide linkage analysis of Kawasaki disease: evidence for linkage to chromosome 12. (2007)
  • Author(s): Onouchi Y, Tamari M, Takahashi A, Tsunoda T, Yashiro M, Nakamura Y, Yanagawa H, Wakui K, Fukushima Y, Kawasaki T, Nakamura Y, Hata A.
  • Journal Title: J Hum Genet 52 Pages: 179-190
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes. (2007)
  • Author(s): Kosho T, Takahashi J, Momose T, Nakamura A, Sakurai A, Wada T, Yoshida K, Wakui K, Suzuki T, Kasuga K, Nishimura G, Kato H, Fukushima Y.
  • Journal Title: Am J Med Genet 43A Pages: 2598-2603
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] A complex karyotype, including a three-way translocation generating a NUP98-HOXD13 transcript, in an infant with acute myeloid leukemia (2007)
  • Author(s): Hidaka, E., Tanaka, M., Matsuda, K., Ishikawa-Matsumura, M., Yamauchi, K., Sano, K., Honda, T., Wakui, K., Yanagisawa, R., Nakazawa, Y., Sakashita, K., Shiohara, M., Ishii, E., Koike, K
  • Journal Title: Cancer Genet Cytogenet 176 Pages: 137-413
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A genomewide linkage analysis of Kawasaki disease : evidence for linkage to chromosome 12 (2007)
  • Author(s): Onouchi, Y., Tamari, M., Takahashi, A., Tsunoda, T., Yashiro, M., Nakamura, Y., Yanagawa, H., Wakui, K., Fukushima, Y., Kawasaki, T., Nakamura, Y., Hata, A
  • Journal Title: J Hum Genet 52 Pages: 179-190
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mandibuloacral dysplasia and a novel LMNA mutation in a woman with severe progressive skeletal changes (2007)
  • Author(s): Kosho, T., Takahashi, J., Momose, T., Nakamura, A., Sakurai, A., Wada, T., Yoshida, K., Wakui, K., Suzuki, T., Kasuga, K., Nishimuth, G., Kato, H., Fukushima, Y
  • Journal Title: Am J Med Genet 43A Pages: 2598-2603
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Discrepancies of the results between MLPA and FISH, and between MLPA kits, observed in a case of subtelomeric imbalances of chromosome 12. (2007)
  • Author(s): Wakui K, Kinishita Y, Furui Y, Shinogi K, Fukui T, Kawamura R, Gondo N, Yokoyama S, Higashi H, Fukushima Y.
  • Organizer: The American Society of Human Genetics
  • Place of Presentation: San Diego, USA
  • Year and Date: 20071023-26
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Discrepancies of the results between MLPA and FISH, and between MLPA kits, observed in a case of subtelomeric imbalances of chromosome 12 (2007)
  • Author(s): Wakui, K., Kinishita, Y., Furui, Y., Shinogi, K., Fukui, T., Kawamura, R., Gonda N., Yokoyama, S., Higashi, H., Fukushima, Y
  • Organizer: The American Society of Human Genetics
  • Place of Presentation: San Diego, USA
  • Year and Date: 20071023-26
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Subtelomeric FISH法により確認されたpure dup 9q34の一例 (2007)
  • Author(s): 今川 英里, 古庄 知己, 松田 和之, 樋口 由美子, 宇原 美帆, 山内 一由, 勝山努, 日高 惠以子, 柴 直子, 荒井 史, 涌井 敬子, 福嶋 義光
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] MLPA法による染色体サブテロメア量的不均衡についての解析結果とその細胞遺伝学的解釈について (2007)
  • Author(s): 涌井 敬子, 古井 陽介, 篠木 加奈, 福井 崇史, 河村 理恵, 木下 由子, 古庄 知己, 和田 敬仁, 横山 士郎, 東 央晋, 福嶋 義光
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-15
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] A case of pure dup 9q34 confirmed by Subtelomeric FISH analyses (2007)
  • Author(s): Imagawa, E., Kosho, T., Matsuda, K., Higuchi, Y., Uhara, M., Yamauchi, K., Katuyama, T., Hidaka, E., Shiba, N., Arai, F., Wakui, K., Fukushima, Y
  • Organizer: The Japan Society of Human Genetics
  • Place of Presentation: Tokyo
  • Year and Date: 2007-09-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Analytical validity on MLPA method for detecting subtelomeric irnbalances (2007)
  • Author(s): Wakui, K., Furui, Y., Shinogi, K. Fukui, T., Kawamura, R., Kosho, T., Wada, T., Yokoyama, S., Higashi, H., Fukushima, Y
  • Organizer: The Japan Society of Human Genetics
  • Place of Presentation: Tokyo
  • Year and Date: 2007-09-15
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] 10Mb以上の欠失と稀な合併症を伴う1p36欠失症候群の一例 (2007)
  • Author(s): 河村 理恵, 涌井 敬子, 齋藤 章治, 和田 敬仁, 加藤 光広, 古庄 知己, 福嶋 義光.
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 12番染色体構造異常例における分子細胞遺伝学的サブテロメアの解析と結果解釈の留意点 (2007)
  • Author(s): 木下 由子, 涌井 敬子, 古井 陽介, 篠木 加奈, 福井 崇史, 河村 理恵, 横山士郎, 東 央晋, 福嶋 義光
  • Organizer: 日本人類遺伝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-09-13
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] A Ipso deletion syndrome with >10Mb deletion and uncommon clinical features (2007)
  • Author(s): Kawamura, R., Wakui, K., Saito, S., Wada, T., Kato, K., Kosho, T., Fukushima, Y
  • Organizer: The Japan Society of Human Genetics
  • Place of Presentation: Tokyo
  • Year and Date: 2007-09-13
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Molecular cytogenetic analysis of subtelomeric regions for a structural abnormalities of chromosome 12 and interpretations of the results (2007)
  • Author(s): Kinishita, Y., Wakui, K., Furui, T., Shinogi, K., Fukui, T., Kawamura, R., Yokoyama, S., Higashi, H., Fukushima, Y
  • Organizer: The Japan Society of Human Genetics
  • Place of Presentation: Tokyo
  • Year and Date: 2007-09-13
  • Description: 「研究成果報告書概要(欧文)」より