Detection of chromosomal submicroscopic changes in spontaneous abortion by DNA microarray

• Project/Area Number: 14572143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: Yokohama city graduate school of Medicine (2003); Nagasaki University (2002)
• Principal Investigator: MATSUMOTO Naomichi Yokohama City Graduate School of Medicine, Human Genetics, Professor, 大学院・医学研究科, 教授 (80325638)
• Project Period (FY): 2002 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,000,000 (Direct Cost: ¥3,000,000); Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
• Keywords: DNA microarray / BAC / Genome / Structural abnormality / Spontaneous abortion / DNAマイクロアレー / 染色体微細構造異常 / FISH

Research Abstract

To evaluate submicroscopic chromosomal abnormalities in spontaneous abortions, we developed DNA microarray CGH system.
1)Subtelomere specific microarray : BAC and PAC clones mapped uniquely to each subtelomeric region of human chromosomes were all spotted onto the slide glass. to confirm the reliability of detecting cryptic subtelomeric rearrangements, we analyzed five cases of Wolf-Hirschhorn syndrome (WHS) who were known to have a distal 4p deletion. The microarray CGH system successfully enabled to reveal that two of the five WHS cases had 5q trisomy or 10q trisomy in addition to 4p deletions in all. We then analyzed 69 cases of idiopathic mental retardation (MR) whose karyotype was cryptic subtelomeric rearrangements in for (5.8%) of the 69 MR patients.
2)Whole genome microarray : We fished a total of 2000 BACs evenly spaced through the whole human genome, and confirmed all clones used for microarray were precisely mapped to where they were supposed show signal uniquely. We are now developing the whole genome array. Once it is established, we will analyze spontaneous aborted samples.

Research Products

• [Publications] Kurotaki N, et al.: "Fifty microdeletions among 112 cases of Sotos syndrome : Low copy repeats possibly mediate the common deletion"Hum Mut. 22. 378-387 (2003)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Harada N, et al.: "Subtelomere-specific microarray-based comparative genomic hybridization : A rapid detection system for cryptic re-arrangement in idiopathic mental retardation"J Med Genet. 41. 130-136 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Iwakoshi M, et al.: "9q34.3 deletion syndrome in three unrelated children"Am J Med Genet. 126A. 278-283 (2004)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kurosawa K, et al.: "Unmasking 15q microdeletion in a mentally retarded boy with r(Y) by microarray-based comparative genomic hybridization"Am J Med Genet. (in press).
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kurotaki N, Harada N, Shimokawa O, Miyake N, Kawame H, Uetake K, Makita Y, Kondoh T, Ogata T, Hasegawa T, Nagai N, Ozaki T, Touyama T, Shenhav R, Ohashi H, Medne L, Shiihara T, Ohtsu S, Kato Z, Okamoto N, Nishimoto J, Lev D, Miyoshi Y, Ishikiriyama S, Sonoda T, Sakazume S, Fukushima Y, Kurosawa K, Cheng J-F, Yoshiura K-i, Ohta T, Kishino T, Niikawa N, Matsumoto N: "Fifty microdeletions among 112 cases of Sotos syndrome : Low copy repeats possibly mediate the common deletion."Hum Mut. 22(5). 348-387 (2003)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Harada N, Hatchwell E, Okamoto N, Tsukahara M, Kurosawa K, Kawame H, Kondoh T, Ohashi H, Tsukino R, Kondoh Y, Shimokawa O, Ida T, Nagai T, Fukushima Y, Niikawa N, Matsumoto N.: "Subtelomere-specific Microarray-based Comparative Genomic Hybridization : A Rapid Detection System for Cryptic Rearrangements in Idiopathic Mental Retardation."J Med Gent. 41. 130-136 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Iwakoshi M, Okamoto N, Harada N, Nakamura T, Yamamori S, Fujita H, Niikawa N, Matsumoto N.: "9q34.3 deletion syndrome in three unrelated children. Am J Med Genet 126A(3):278-283,2004"Am J Med Genet. 126A(3). 278-283 (2004)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kurosawa K, Harada N, Saitoh S, Sosonkina N, Niikawa N, Matsumoto N.: "Unmasking 15q microdeletion in a mentally retarded boy with r(y) by Microarray-based Comparative Genomic Hybridization."Am J Med Genet. (in press).
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kurotaki N et al.: "Fifty microdeletions among 112 cases of Sotos syndrome : Low copy repeats possibly mediate the common deletion"Hum Mut. 22・5. 378-387 (2003)
• [Publications] Harada N et al.: "Subtelomere-specific Microarray-based Comparative Genomic Hybridization : A Rapid Detection System for Cryptic Rearrangements in Idiopathic Mental Retardation"J Med Genet. 41・2. 130-136 (2004)
• [Publications] Iwakoshi M et al.: "9q34.3 deletion syndrome in three unrelated children"Am J Med Genet. (In press). (2004)
• [Publications] Kurosawa K et al.: "Unmasking of 15q Microdeletion in a Mentally Retarded boy With r(Y) by Microarray-based Comparative Genomic Hybridization"Am J Med Genet. (In press).
• [Publications] Harada N: "A 4q21-q22 deletion in a girl with severe growth retardation"Clin Genet. 61・3. 226-228 (2002)
• [Publications] Kurotaki N: "Haploinsufficiency of the NSD1 gene causes Sotos syndrome"Nat Genet. 30・4. 365-366 (2002)
• [Publications] Harada N: "Duplication of 8p23.2 : a benign cytogenetic variant ?"Am J Med Genet. 111・3. 285-288 (2002)
• [Publications] Sugawara H: "Breakpoint analysis of a familial balanced translocation t(2;8)(q31;p21) associated with mesomelic dysplasia"J Med Genet. 39・7. E34 (2002)
• [Publications] Harada N: "A 4-Mb critical region for IUGR at 15q26"Clin Genet. 62・4. 340-342 (2002)
• [Publications] Hoglund P: "Familial Solos syndrome is caused by a novel one base pair deletion of the NSD1 gene"J Med Genet. 40・1. 51-54 (2003)