2002 Fiscal Year Annual Research Report

骨粗鬆症およびゲノム刷り込み関連遺伝子群の解明

Research Project

Project/Area Number	12204010
Research Institution	Nagasaki University
Principal Investigator	新川詔夫長崎大学, 医学部, 教授 (00111170)
Co-Investigator(Kenkyū-buntansha)	木住野達也長崎大学, 遺伝子実験施設, 助教授 (70315232)
Keywords	骨粗鬆症 / ゲノム刷り込み / 刷り込み遺伝子 / TGFB遺伝子 / TGFB1遺伝子 / 1塩基多型(SNP) / 関連解析 / 骨軟化症
Research Abstract	TGFB1およびその関連遺伝子内のSNP同定:骨粗鬆症の候補遺伝子であるTGFB1とTGFBR1の他に、TGFB1,TGFBR1,TGFBR2,SMAD2,SMAD3,SMAD4,SM4D7内に106のSNP(新規SNP79種)と他の11多型(新規)、およびIFNB1,IFNAR1,FOS遺伝子内の19のSNPs(新規SNP8種)を同定し、96名の正常集団での各アレル頻度を算出した。骨粗鬆症患者における関連解析:上記SNPsを用いて、H地方から骨粗鬆症患者118名と骨軟化症患者118名、N地方から地域集団検診者中、骨密度低下の50名を集積した。TGFB1-29T/C、3435C/T、2085A/G、2484T/C、および2691G/Tは、H地方では骨粗鬆症との相関(P=0.14〜0.46)および骨軟化症との相関(P=0.35〜0.77)はいずれも検出されなかった。N地方の骨粗鬆症ではTGFB1,TGFB2,SMAD2,SMAD3,SMAD4,IFNB1,IFNAR1,FOS遺伝子の各SNPsとの相関を調べたが、いずれも相関はみられなかった。変異Tgfb1モデルマウスの作成と解析:骨密度増加患者で同定されるR218C変異をマウスES細胞に導入し、目的とする相同組換体、次いでマウス胚に同組換体を移植し8匹のキメラ個体を得た。しかし、これらのマウスはすべて不妊であり、非キメラ変異個体を得ることができなかった。 7q32刷り込み遺伝子の解析:マウス・ヒト雑種体細胞パネルにおけるEST発現をRT-PCRにて解析し、新規刷り込み遺伝子EST stSG46233(父性発現)とstSG21174,stSG8865,R30646(各々母性発現)を同定した。一方、MEST周辺の転写地図から、13遺伝子を新たにマップした。これらの遺伝子を胎児組織を用いて網羅的に解析し、同領域における刷り込み遺伝子を同定した。このうち、刷り込みを証明したのはCIT1とCPA3の2種であった。CPA3は胎児心・肺・腎・脾で部分的刷り込み、不死化EB細胞系では完全な刷り込み(母性発現)を証明した。

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 painting"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 (SNPs) and 11 other types of variations in genes for transforming growth factor-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 IGF1R?"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 NSD1 : 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

骨粗鬆症およびゲノム刷り込み関連遺伝子群の解明

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 painting"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 (SNPs) and 11 other types of variations in genes for transforming growth factor-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 IGF1R?"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 NSD1 : 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)