DEVELOPMENT OF QUANTITATIVE METHODS FOR SINGLE NUCLEOTIDE POLYMORPHISMS ANALYSIS AND ITS APPLICATION IN MEDICAL GENETICS

2009 Fiscal Year Final Research Report

• Project/Area Number: 17019051
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University
• Principal Investigator: TAHIRA Tomoko Kyushu University, 生体防御医学研究所, 助教 (50155230)
• Co-Investigator(Kenkyū-buntansha): HAYASHI Kenshi 九州大学, 生体防御医学研究所, 特任教授 (00019671) ; HORIUCHI Takahiko 九州大学, 大学病院, 准教授 (90219212) ; KUKITA Yoji 大阪府立病院機構, 大阪府立成人病センター研究所, 研究員 (60372744) ; HIGASA Koichiro 九州大学, 学術研究員 (10419583)
• Project Period (FY): 2005 – 2009
• Keywords: SNP / 疾患関連解析 / 自己免疫疾患 / SSCP / ハプロタイプ / データベース

Research Abstract

We have established the cost-effective and reliable pooling-based methods for genome-wide association study. This method screens disease-associated regions by determining allele frequencies of SNPs in pooled DNA first by microarray analysis and then by quantitative SSCP analysis. Using this method, we detected many disease-related genes of systemic lupus erythematosus. We also determined definitive haplotype consisting of SNPs and copy number polymorphisms by genotyping duplicated haploid genomes of complete hydatidiform moles. This linkage disequilibrium information of Japanese genome has been made available from "D-HaploDB".

Research Products

• [Journal Article] A definitive haplotype map as determined by genotyping duplicated haploid genomes finds a predominant haplotype preference at copy number variation events. (2010)
  • Author(s): Kukita Y, Yahara K, Tahira T, Higasa K, Sonoda M, Yamamoto K, Kato K, Wake N, Hayashi K.
  • Journal Title: Am.J.Hum.Genet. 86(6) Pages: 918-928
  • Peer Reviewed
• [Journal Article] Evaluation of haplotype inference using definitive haplotype data obtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions. (2009)
  • Author(s): Higasa K, Kukita Y, Kato K, Wake N, Tahira T, Hayashi K.
  • Journal Title: PLoS Genetics 5(5) Pages: e1000468
  • Peer Reviewed
• [Journal Article] Estimation of SNP allele frequencies by SSCP analysis of poolepooleolepooleleNA. (2009)
  • Author(s): Tahira T, Kukita Y, Higasa K, Okazaki Y, Yoshinaga A, Hayashi K.
  • Journal Title: Methods in Molecular Biology 578 Pages: 193-207
• [Journal Article] Prevalence of copy number neutral LOH in glioblastomas revealed by genome-wide analysis of laser- microdissected tissues. (2008)
  • Author(s): Kuga D, Mizoguchi M, Guan Y, Hata N, Yoshimoto K, Shono T, Suzuki SO, Kukita Y, Tahira T, Nagata S, Sasaki T, Hayashi K.
  • Journal Title: Neuro Oncol 10(6) Pages: 995-1003
  • Peer Reviewed
• [Journal Article] Association of polymorphisms in complement component C3 gene with susceptibility to systemic lupus erythematosus. (2008)
  • Author(s): Miyagawa H, Yamai M, Sakaguchi D, Kiyohara C, Tsukamoto H, Kimoto Y, Nakamura T, Lee J-H, Tsai C-Y, Chiang B-L, Nagasawa K, Harada M, Tahira T, Hayashi K, Horiuchi T.
  • Journal Title: Rheumatology 47(2) Pages: 158-164
  • Peer Reviewed
• [Journal Article] Narrowing the regions of allelic losses of chromosome 1p36 in meningioma tissues by an improved SSCP analysis. (2008)
  • Author(s): Guan Y, Hata N, Kuga D, Yoshimoto K, Mizoguchi M, Shono T, Suzuki S, Tahira T, Kukita Y, Higasa K, Yokoyama N, Nagata S, Iwaki T, Sasaki T, Hayashi K.
  • Journal Title: Int.J.Cancer 122(8) Pages: 1820-1826
  • Peer Reviewed
• [Journal Article] Moderate reduction of Norrin signaling activity associated with the causative missense mutations identified in patients with familial exudative vitreoretinopathy. (2008)
  • Author(s): Qin M, Kondo H, Tahira T, Hayashi K.
  • Journal Title: Human Genetics 122(6) Pages: 615-623
  • Peer Reviewed
• [Journal Article] Severe form of familial exudative vitreoretinopathy caused by homozygous R417Q mutation in frizzled-4 gene. (2007)
  • Author(s): Kondo H, Qin M, Tahira T, Hayashi K.
  • Journal Title: Ophthalmic Genetics 28(4) Pages: 220-223
  • Peer Reviewed
• [Journal Article] Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy. (2007)
  • Author(s): Kondo H, Qin M, Kusaka S, Tahira T, Hasebe H, Hayashi H, Uchio E, Hayashi K.
  • Journal Title: Invest.Ophthalmol.Vis.Sci 48(3) Pages: 1276-1282
  • Peer Reviewed
• [Journal Article] D-HaploDB : a database of definitive haplotypes determined by genotyping complete hydatidiform mole samples. (2007)
  • Author(s): Higasa K, Miyatake K, Kukita Y, Tahira T, Hayashi K.
  • Journal Title: Nucleic Acids Res. 35 Pages: D685-D689
  • Peer Reviewed
• [Journal Article] A functional M196R polymorphism of tumor necrosis factor receptor type 2 is associated with systemic lupus erythematosus : a case-control study and a meta-analysis. (2007)
  • Author(s): Horiuchi T, Kiyohara C, Tsukamoto H, Okamura S, Nagasawa K, Harada M., et al.
  • Journal Title: Ann.Rheum.Dis. 66(3) Pages: 320-324
  • Peer Reviewed
• [Journal Article] Novel OPA1 mutations identified in Japanese pedigrees with optic atrophy. (2006)
  • Author(s): Qin M, Kondo H, Uno H, Fujiwara E, Uchino E, Tahira T, Hayashi K.
  • Journal Title: Molecular Vision 12 Pages: 485-491
  • Peer Reviewed
• [Journal Article] QSNPlite, a software system for quantitative analysis of SNPs based on capillary array SSCP analysis. (2006)
  • Author(s): Tahira T, Okazaki Y, Miura K, Yoshinaga A, Masumoto K, Higasa K, Kukita Y, Hayashi K.
  • Journal Title: Electrophoresis 27(19) Pages: 3869-3878
  • Peer Reviewed
• [Journal Article] Optimization of capillary array electrophoresis single strand conformation polymorphism analysis for routine molecular diagnostics. (2006)
  • Author(s): Jespersgaard C, Larsen LA, Baba S, Kukita Y, Tahira T, Christiansen M, Vuust J, Hayashi K, Andersen PS.
  • Journal Title: Electrophoresis 27(19) Pages: 3816-3822
  • Peer Reviewed
• [Journal Article] Periodicity of SNP distribution around transcription start sites. (2006)
  • Author(s): Higasa K, Hayashi K.
  • Journal Title: BMC Genomics 7 Pages: 66
• [Journal Article] Allelic Losses of Chromosome 10 in Glioma Tissues Detected by Quantitative Single-Strand Conformation Polymorphism Analysis. (2006)
  • Author(s): Hata N, Yoshimoto K, Yokoyama N, Mizoguchi M, Shono T, Guan Y, Tahira T, Kukita Y, Higasa K, Nagata S, Iwaki T, Sasaki T, Hayashi K.
  • Journal Title: Clin.Chem 52(3) Pages: 370-378
  • Peer Reviewed
• [Journal Article] Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT. (2005)
  • Author(s): Horiuchi T, Gondo H, Miyagawa H, Otsuka J, Inaba S, Nagafuji K, Takase K, Tsukamoto H, Koyama T, Mitoma H, Tamimoto Y, Miyagi Y, Tahira T, Hayashi K, Hashimura C, Okamura S, Harada M.
  • Journal Title: Gene Immun 6(2) Pages: 162-166
  • Peer Reviewed
• [Journal Article] Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. (2005)
  • Author(s): Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H.
  • Journal Title: Human Mutation 26(2) Pages: 104-112
  • Peer Reviewed
• [Journal Article] dbQSNP : a database of SNPs in human promoter regions with allele frequency information determined by single-strand conformation polymorphism- based method. (2005)
  • Author(s): Tahira T, Baba S, Higasa K, Kukita Y, Suzuki Y, Sugano S, Hayashi K.
  • Journal Title: Human Mutation 26(2) Pages: 69-77
  • Peer Reviewed
• [Journal Article] Genome-wide definitive haplotypes determined using a collection of complete hydatidiform moles. (2005)
  • Author(s): Kukita Y, Miyatake K, Stokowski R, Hinds D, Higasa K, Wake N, Hirakawa T, Kato H, Matsuda T, Pant K, Cox D, Tahira T, Hayashi K.
  • Journal Title: Genome Res. 15(11) Pages: 1511-1518
  • Peer Reviewed
• [Presentation] Definitive SNP/CNV haplotyping of Asian genomes using DNAs derived from complete hydatidiform moles. (2009)
  • Author(s): Hayashi K, et al.
  • Organizer: 58th Annual Meeting of American Society of Human Genetics.
  • Place of Presentation: Honolulu, U.S.A.
  • Year and Date: 2009-10-23
• [Presentation] Identification of loci for systemic lupus erythematosus by pooling-based genome-wide association study. (2008)
  • Author(s): Tahira T, et al.
  • Organizer: 57th Annual Meeting of the American Society of Human Genetics
  • Place of Presentation: Philadelphia, U.S.A.
  • Year and Date: 2008-11-12
• [Presentation] D-haplo : a genome-wide definitive haplotype determined using complete hydatidiform moles. (2006)
  • Author(s): Hayashi K.
  • Organizer: The 8th international meeting on human genome variation and complex genome analysis (HGV2006)
  • Place of Presentation: Hong Kong, SAR, China(招待講演)
  • Year and Date: 2006-09-14
• [Book] PCR-SSCP法実験医学別冊「新遺伝子工学ハンドブック」改訂第5版 (2010)
  • Author(s): 田平知子
  • Total Pages: 110-114
  • Publisher: 林健志羊土社
• [Book] SNP ゲノタイピング(総論) 「DNAチップ/マイクロアレイ臨床応用の実際」(油谷浩幸編) (2008)
  • Author(s): 久木田洋児, 林健志
  • Total Pages: 105-110
  • Publisher: メディカルATゥ
• [Book] メンデルからDNAを経てゲノムへ バイオ研究マスターシリーズ「遺伝子工学集中マスター」 (2006)
  • Author(s): 林健志
  • Total Pages: 14-30
  • Publisher: 羊土社
• [Remarks] 「dbQSNP」データベース
  • URL: http://qsnp.gen.kyushu-u.ac.jp/
• [Remarks] 「D-HaploDB」データベース
  • URL: http://orca.gen.kyushu-u.ac.jp/
• [Remarks] 「QSNPlite」ソフトウェア
  • URL: http://qsnp.gen.kyushu-u.ac.jp