2002 Fiscal Year Annual Research Report

コンソーシアムによる単一遺伝子病の連鎖解析と疾患遺伝子同定

Research Project

Project/Area Number	13854024
Research Institution	Nagasaki University
Principal Investigator	新川詔夫長崎大学, 医学部, 教授 (00111170)
Co-Investigator(Kenkyū-buntansha)	塚元和弘長崎大学, 大学院・医歯薬学総合研究科, 助教授 (30253305) 木住野達也長崎大学, 遺伝子実験施設, 助教授 (70315232) 吉浦孝一郎長崎大学, 医学部, 助手 (00304931) 辻田高宏長崎大学, 大学院・医歯薬学総合研究科, 講師 (40304919) 松本正長崎大学, 医学部, 教授 (70190535)
Keywords	連鎖解析 / 遺伝子病 / ハプロタイプ解析 / 家族性側索硬化症 / 無臭覚症 / 多汗症 / 緊張性四肢麻痺 / 疾患遺伝子座
Research Abstract	平成14年度は、我が国で発見された4種の未知遺伝病(遺伝形質、全て常染色体優性)の連鎖解析と、3種の遺伝病の原因遺伝子の位置的候補遺伝子探索を行った。 (1)家族性側索硬化症(ALS):九州1地域にみられる常染色体優性の家族性ALSの1家系(31名の構成員中、罹患者14名)について、マイクロサテライトマーカーパネルを利用したアレルタイピング(ゲノムスキャン)を行った。ハプロタイプ解析の結果、8番染色体領域が連鎖候補領域として矛盾がなかった。現在さらに、家族構成員および同領域マーカーを増加してさらにタイピングを行い、領域の狭小化を行っている。 (2)無嗅覚症:イラン人の2つの大家系(計166名の構成員中、罹患者12名)について、(1)と同様の連鎖解析およびハプロタイプ解析を行った。現在18番染色体上の47cMまで狭めている。 (3)緊張性四肢麻痺:49名中16名が罹患している遅発性家族性緊張性四肢麻痺の1家系、および19名中6名の罹患者がいる1家系、計2家系について、同様に連鎖解析を行っている。連鎖候補領域が数ヶ所得られたが、未だ確定していない。 (4)常染色体優性多汗症:数名〜数十名の罹患者がいる27家系について、同様に連鎖解析を開始した。 (5)変異解析:平成13年度までの連鎖解析で疾患座の局在を明らかにしたBardet-Biedl症候群3型、後水晶体線維型先天盲、家族性合指症1型、血小板減少症、肢中部異形成症、van der Woude症候群(VWS)について、連鎖領域に存在する遺伝子群の変異解析を行った。van der Woude症候群と肢中部異形成症を除いて、現在70種を越える遺伝子のスクリーニングを終了したが、いずれの疾患についても未だ変異は同定されていない。VWSでは、IRF6遺伝子中に変異[1234del(C)]を同定した。また肢中部異形成症では別の染色体転座症例で切断点クローニングを行ったが、切断点には遺伝子は存在しなかった。

Research Products

(25 results)

All Other

All Publications (25 results)

[Publications] Imaizumi K, et al.: "Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1)"American Journal of Medical Genetics. 107. 58-60 (2002)
[Publications] Nishimura G, et al.: "Camurati-Engelmann disease Type II : Progressive diaphyseal dysplasia with striations of the bones"American Journal of Medical Genetics. 107. 5-11 (2002)
[Publications] Kayashima T, et al.: "Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene(GNE)"Journal of Human Genetics. 47. 77-79 (2002)
[Publications] Ida T, et al.: "Identification of de novo chromosome rearrangements : Five cases analyzed with differential chromosome panting"American Journal of Medical Genetics. 108. 182-186 (2002)
[Publications] Kayashima T, et al.: "Maternal isodisomy for 14q21-q24 in a man with diabetes mellitus"American Journal of Medical Genetics. 111. 38-42 (2002)
[Publications] Kurotaki N, et al.: "Haploinsufficiency of the NSD1 gene causes Sotos Syndrome"Nature Genetics. 30. 365-366 (2002)
[Publications] Tomita H-A, et al.: "The wet/dry earwax locus maps to chromosome 16p11.2-16q12.1"Lancet. 359. 2000-2002 (2002)
[Publications] Kondo S, et al.: "A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with mirror-image polydactyly of hands and feet"Journal of Human Genetics. 47. 136-139 (2002)
[Publications] Sugawara H, et al.: "Breakpoint analysis of a familial balanced translocation t(2;8)(q31;p21) associated with mesomelic dysplasia"Journal of Medical Genetics. 39. e34 (2002)
[Publications] Komatsu K, et al.: "Confirmation of genetic homogeneity of non-syndromic low frequency sensorineural hearing loss by linkage analysis and DFNA6/14 mutations in a Japanese family"Journal of Human Genetics. 47. 395-399 (2002)
[Publications] Harada N, et al.: "Duplication of 8p23.2 : A benign cytogentic variant?"American Journal of Medical Genetics. 111. 285-288 (2002)
[Publications] Watanabe Y, et al.: "A catalog of 106 single nucleotide polymorphisms (11) and 11 other types of variations in genes for transforming growth fact-β1 (TGF-β1) and its signaling pathway"Journal of Human Genetics. 47. 478-483 (2002)
[Publications] Yamada T, et al.: "The novel gene, TSGA14, adjacent to the imprinted gene MEST escapes genomic imprinting"Gene. 288. 57-63 (2002)
[Publications] Harada N, et al.: "A 4q21-q22 deletion in a girl with severe growth retardation"Clinical Genetics. 61. 226-228 (2002)
[Publications] Miyamoto T et al.: "The human ASCL2 gene escaping genomic imprinting and its expression pattern"Journal of Assisted Reproduction and Genetics. 19. 240-244 (2002)
[Publications] Nagai T et al.: "Postnatal overgrowth by 15q-trisomy and intrauterine growth retardation by 15q-monosomy due to familial translocation t(13;15):Dosage effect of IGFIR?"American Journal of Medical Genetics. 113. 173-177 (2002)
[Publications] Matsumoto N, Niikawa N: "Kabuki make-up syndrome : A Review"American Journal of Medical Genetics. (In press). (2003)
[Publications] Masumoto J et al.: "ASC, a novel 22-kDa protein aggregates during apoptosis of human promyelocytic leukemia HL-60 cells"Journal of Biological Chemistry. (In press). (2003)
[Publications] Kayashima T, et al.: "Atp10a/pfatp, the mouse ortholog of the human imprinted ATP10C gene, escapes genomic imprinting"Human Genetics. (In press). (2003)
[Publications] Harada N et al.: "Sotos syndrome and haploinsufficiency of NSDl : Phenotypic comparison between intragenic mutations and submicroscopic deletions"Journal of Medical Genetics. (In press). (2003)
[Publications] Peeters H et al.: "PA26 is a candidate gene for heterotaxia in humans : Identification of a novel, PA26-related gene family in human and mouse"Human Genetics. (In press). (2003)
[Publications] Kondoh Y et al.: "Inv dup del(4)(:p14->p16.3::p16.3->qter) with manifestations of partial duplication 4p and Wolf-Hirschhorn syndrome"American Journal of Medical Genetics. (in press). (2003)
[Publications] Shotelersuk V et al.: "A novel mutation, 1234del(C), of the IRF6 in a Thai family with van der Woude syndrome"International Journal of Molecular Medicine. (in press). (2003)
[Publications] Miyake N et al.: "Preferential paternal origin of microdeletion as prezygotic chromosome and/or chromatid rearrangements in Sotos syndrome"American Journal of Human Genetics. (in press). (2003)
[Publications] Ida T, et al.: "Functional disomy for Xq22-q23 with complex rearrangements involving chromosomes 3 and X in a mentally and physically retarded girl"American Journal of Medical Genetics. (in press). (2003)

2002 Fiscal Year Annual Research Report

コンソーシアムによる単一遺伝子病の連鎖解析と疾患遺伝子同定

Principal Investigator

新川 詔夫 長崎大学, 医学部, 教授 (00111170)

Research Products

[Publications] Imaizumi K, et al.: "Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1)"American Journal of Medical Genetics. 107. 58-60 (2002)

[Publications] Nishimura G, et al.: "Camurati-Engelmann disease Type II : Progressive diaphyseal dysplasia with striations of the bones"American Journal of Medical Genetics. 107. 5-11 (2002)

[Publications] Kayashima T, et al.: "Nonaka myopathy is caused by mutations in the UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase gene(GNE)"Journal of Human Genetics. 47. 77-79 (2002)

[Publications] Ida T, et al.: "Identification of de novo chromosome rearrangements : Five cases analyzed with differential chromosome panting"American Journal of Medical Genetics. 108. 182-186 (2002)

[Publications] Kayashima T, et al.: "Maternal isodisomy for 14q21-q24 in a man with diabetes mellitus"American Journal of Medical Genetics. 111. 38-42 (2002)

[Publications] Kurotaki N, et al.: "Haploinsufficiency of the NSD1 gene causes Sotos Syndrome"Nature Genetics. 30. 365-366 (2002)

[Publications] Tomita H-A, et al.: "The wet/dry earwax locus maps to chromosome 16p11.2-16q12.1"Lancet. 359. 2000-2002 (2002)

[Publications] Kondo S, et al.: "A novel gene is disrupted at a 14q13 breakpoint of t(2;14) in a patient with mirror-image polydactyly of hands and feet"Journal of Human Genetics. 47. 136-139 (2002)

[Publications] Sugawara H, et al.: "Breakpoint analysis of a familial balanced translocation t(2;8)(q31;p21) associated with mesomelic dysplasia"Journal of Medical Genetics. 39. e34 (2002)

[Publications] Komatsu K, et al.: "Confirmation of genetic homogeneity of non-syndromic low frequency sensorineural hearing loss by linkage analysis and DFNA6/14 mutations in a Japanese family"Journal of Human Genetics. 47. 395-399 (2002)

[Publications] Harada N, et al.: "Duplication of 8p23.2 : A benign cytogentic variant?"American Journal of Medical Genetics. 111. 285-288 (2002)

[Publications] Watanabe Y, et al.: "A catalog of 106 single nucleotide polymorphisms (11) and 11 other types of variations in genes for transforming growth fact-β1 (TGF-β1) and its signaling pathway"Journal of Human Genetics. 47. 478-483 (2002)

[Publications] Yamada T, et al.: "The novel gene, TSGA14, adjacent to the imprinted gene MEST escapes genomic imprinting"Gene. 288. 57-63 (2002)

[Publications] Harada N, et al.: "A 4q21-q22 deletion in a girl with severe growth retardation"Clinical Genetics. 61. 226-228 (2002)

[Publications] Miyamoto T et al.: "The human ASCL2 gene escaping genomic imprinting and its expression pattern"Journal of Assisted Reproduction and Genetics. 19. 240-244 (2002)

[Publications] Nagai T et al.: "Postnatal overgrowth by 15q-trisomy and intrauterine growth retardation by 15q-monosomy due to familial translocation t(13;15):Dosage effect of IGFIR?"American Journal of Medical Genetics. 113. 173-177 (2002)

[Publications] Matsumoto N, Niikawa N: "Kabuki make-up syndrome : A Review"American Journal of Medical Genetics. (In press). (2003)

[Publications] Masumoto J et al.: "ASC, a novel 22-kDa protein aggregates during apoptosis of human promyelocytic leukemia HL-60 cells"Journal of Biological Chemistry. (In press). (2003)

[Publications] Kayashima T, et al.: "Atp10a/pfatp, the mouse ortholog of the human imprinted ATP10C gene, escapes genomic imprinting"Human Genetics. (In press). (2003)

[Publications] Harada N et al.: "Sotos syndrome and haploinsufficiency of NSDl : Phenotypic comparison between intragenic mutations and submicroscopic deletions"Journal of Medical Genetics. (In press). (2003)

[Publications] Peeters H et al.: "PA26 is a candidate gene for heterotaxia in humans : Identification of a novel, PA26-related gene family in human and mouse"Human Genetics. (In press). (2003)

[Publications] Kondoh Y et al.: "Inv dup del(4)(:p14->p16.3::p16.3->qter) with manifestations of partial duplication 4p and Wolf-Hirschhorn syndrome"American Journal of Medical Genetics. (in press). (2003)

[Publications] Shotelersuk V et al.: "A novel mutation, 1234del(C), of the IRF6 in a Thai family with van der Woude syndrome"International Journal of Molecular Medicine. (in press). (2003)

[Publications] Miyake N et al.: "Preferential paternal origin of microdeletion as prezygotic chromosome and/or chromatid rearrangements in Sotos syndrome"American Journal of Human Genetics. (in press). (2003)

[Publications] Ida T, et al.: "Functional disomy for Xq22-q23 with complex rearrangements involving chromosomes 3 and X in a mentally and physically retarded girl"American Journal of Medical Genetics. (in press). (2003)

新川詔夫長崎大学, 医学部, 教授 (00111170)