2000 年度実績報告書

小児の脳障害に関連する遺伝子群を解明するための新しいシステムの開発

研究課題

研究課題/領域番号	11170236
研究機関	鳥取大学
研究代表者	難波栄二鳥取大学, 遺伝子実験施設, 助教授 (40237631)
研究分担者	小枝達也鳥取大学, 教育地域科学部, 教授 (70225390) 岡明鳥取大学, 医学部, 助教授 (00251273)
キーワード	小児 / 脳障害 / 遺伝的背景 / 単一遺伝 / 多因子遺伝 / 自閉症 / セロトニン / インプリンティング
研究概要	【目的】小児の脳障害には様々な遺伝子が関係するがその多くは末だ解明されていない。そこで本研究は、単一遺伝子病やさらに頻度の高い疾患も含め、それらに関連する遺伝群を解明することを目的とした。【単一遺伝子病】結節性硬化症をはじめとする単一遺伝子病の解析システムは確立でき、様々な脳障害を引き起こす患者の遺伝子異常が解明できた(研究発表参照)。【自閉症】頻度の高い自閉症に焦点をあてた。本疾患は多因子遺伝と考えられ新たなアプローチが必要であった。自閉症の患者や正常対照のDNAサンプルは鳥取大学および東京大学倫理委員会の承認のもと、インフォームドコンセントを得て収集した。(1)関連遺伝子解析:11のセロトニン代謝関連遺伝子についてプロモーター領域多型やSingle Nucleotide Polymorphisms(SNPs)を検討した。17SNPsを解析したところ4つのSNPs(HTR1A,HTR1B,HTR1D,HTR6)で多型が認められた。従来示唆されていたセロトニントランスポータープロモーター領域多型の関連はなく、HTR1B,HTR1D,HTR6との関連も示されなかった。しかし、HTR1A遺伝子が関連する可能性が示された。(2)インプリンテイング機構からのアプローチ:インプリンティング遺伝子を単離できるシステムとしてマウスA9細胞にヒト染色体を1本のみ保持するライブラリーを構築し研究を進めた。本システムを用いて19番染色体上のPEG3のインプリンティング機構が解析できた。さらにセロトニン関連遺伝子がインプリンティング機構と関連するかどうかを検討した。 HTR1D,HTR1A,HTR1B,HTR1E,HTR5A,HTR3A,HTR2Aの遺伝子発現を検討したが、いずれもインプリンティング機構との関連は示されなかった。

研究成果

(23件)

すべてその他

すべて文献書誌 (23件)

[文献書誌] Murakami F: "Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese."J Hum Genet. 44. 15-17 (1999)
[文献書誌] Zhang H: "Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis : lack of loss of heterozygosity in a lung cyst."Am J Med Genet. 82. 368-370 (1999)
[文献書誌] Ueta E: "A rapid screening method by the polymerase chain reaction-single strand conformation polymorphism using fluorescent labeled primer on automatic sequencer for porcine ryanodine receptor gene mutation."J Animal Genet. 27. 7-13 (1999)
[文献書誌] Kono Y: "Analysis of the CAG repeat number in patient with Huntington's disease."Intern Med. 38. 407-411 (1999)
[文献書誌] Yamamoto T: "A novel mutation (A246T) in exon 6 of the proteolipid protein gene associated with connatal Pelizaeus-Merzbacher disease."Hum Mut. 14. 182 (1999)
[文献書誌] Yamamoto T: "NPC1 gene mutations in Japanese patients with Niemann-Pick discase type C."Hum Genet. 105. 10-16 (1999)
[文献書誌] Zhang H: "Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous selerosis complex."J Hum Genet. 44. 391-396 (1999)
[文献書誌] Oka A: "The up-regulation of metabotropic glutamate receptor 5 (MGluR5) in Down's syndrome brains."Acta Neuropathol. 97. 275-278 (1999)
[文献書誌] Yamamoto T: "A patient with cerebral palsy whose mother had a traffic accident during pregnancy : a diffuse axonal injury?"Brain Dev. 21. 334-336 (1999)
[文献書誌] Kato M: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann Neurol. 47. 514-516 (2000)
[文献書誌] Imai J: "Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients : genetic analysis of the CYP2C9 locus."Pharmacogenetics. 10. 85-89 (2000)
[文献書誌] Ikebuchi M: "The Arg1075His substitution in the FBN1 gene is clinieally innocent for Marfan syndrome."Hum Mut. 15. 298 (2000)
[文献書誌] Chikumi H: "Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome."J Hum Genet. 45. 115-118 (2000)
[文献書誌] Nagata K: "A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome."J Hum Genet. 45. 237-240 (2000)
[文献書誌] Pipo JR: "Two novel serine repeat length polymorphisms (1043insS and 1043insSS) at exon 23 of the TSC1 gene."Hum Mut. 16. 375 (2000)
[文献書誌] Saito Y: "Widespread expression of α-synuelein and tau immunoreactivity in Hallcrvorden-Spatz syndrome with protracted clinical course."J Neurol Sci. 177. 48-59 (2000)
[文献書誌] Tanaka Y: "Congenital myotonic dystrophy : report of paternal transmission."Brain Dev. 22. 132-134 (2000)
[文献書誌] Kurachi Y: "Rapid immunologic diagnosis of classic late infantile neuronal ceroid lipofuseinosis."Neurology. 54. 1676-1680 (2000)
[文献書誌] Oka A: "Expression of DNA-dependent protein kinase catalytic subunit and Ku80 in developing human brains : implication of DNA-repair in neurogenesis."Neuosci Lett. 292. 167-170 (2000)
[文献書誌] Shitoa M: "Cognitive and neurophysiological evaluation of Japanese dyslexia."Brain Dev. 22. 421-426 (2000)
[文献書誌] Yamamoto T: "Genotype-phenotype relationship of Niermann-Pick disease Type C : a possibility correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts."J Med Genet. 37. 707-711 (2000)
[文献書誌] Tsukamoto H: "SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick disease type C."Prenat Diagn. 21. 55-57 (2001)
[文献書誌] Yamamoto T: "DEFECT 11 syndrome associated with agenesis of the corpus callosum."J Med Genet.. 38. E5 (2001)

2000 年度 実績報告書

小児の脳障害に関連する遺伝子群を解明するための新しいシステムの開発

研究代表者

難波 栄二 鳥取大学, 遺伝子実験施設, 助教授 (40237631)

研究成果

[文献書誌] Murakami F: "Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese."J Hum Genet. 44. 15-17 (1999)

[文献書誌] Zhang H: "Novel TSC2 mutation in a patient with pulmonary tuberous sclerosis : lack of loss of heterozygosity in a lung cyst."Am J Med Genet. 82. 368-370 (1999)

[文献書誌] Ueta E: "A rapid screening method by the polymerase chain reaction-single strand conformation polymorphism using fluorescent labeled primer on automatic sequencer for porcine ryanodine receptor gene mutation."J Animal Genet. 27. 7-13 (1999)

[文献書誌] Kono Y: "Analysis of the CAG repeat number in patient with Huntington's disease."Intern Med. 38. 407-411 (1999)

[文献書誌] Yamamoto T: "A novel mutation (A246T) in exon 6 of the proteolipid protein gene associated with connatal Pelizaeus-Merzbacher disease."Hum Mut. 14. 182 (1999)

[文献書誌] Yamamoto T: "NPC1 gene mutations in Japanese patients with Niemann-Pick discase type C."Hum Genet. 105. 10-16 (1999)

[文献書誌] Zhang H: "Mutational analysis of TSC1 and TSC2 genes in Japanese patients with tuberous selerosis complex."J Hum Genet. 44. 391-396 (1999)

[文献書誌] Oka A: "The up-regulation of metabotropic glutamate receptor 5 (MGluR5) in Down's syndrome brains."Acta Neuropathol. 97. 275-278 (1999)

[文献書誌] Yamamoto T: "A patient with cerebral palsy whose mother had a traffic accident during pregnancy : a diffuse axonal injury?"Brain Dev. 21. 334-336 (1999)

[文献書誌] Kato M: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann Neurol. 47. 514-516 (2000)

[文献書誌] Imai J: "Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients : genetic analysis of the CYP2C9 locus."Pharmacogenetics. 10. 85-89 (2000)

[文献書誌] Ikebuchi M: "The Arg1075His substitution in the FBN1 gene is clinieally innocent for Marfan syndrome."Hum Mut. 15. 298 (2000)

[文献書誌] Chikumi H: "Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome."J Hum Genet. 45. 115-118 (2000)

[文献書誌] Nagata K: "A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome."J Hum Genet. 45. 237-240 (2000)

[文献書誌] Pipo JR: "Two novel serine repeat length polymorphisms (1043insS and 1043insSS) at exon 23 of the TSC1 gene."Hum Mut. 16. 375 (2000)

[文献書誌] Saito Y: "Widespread expression of α-synuelein and tau immunoreactivity in Hallcrvorden-Spatz syndrome with protracted clinical course."J Neurol Sci. 177. 48-59 (2000)

[文献書誌] Tanaka Y: "Congenital myotonic dystrophy : report of paternal transmission."Brain Dev. 22. 132-134 (2000)

[文献書誌] Kurachi Y: "Rapid immunologic diagnosis of classic late infantile neuronal ceroid lipofuseinosis."Neurology. 54. 1676-1680 (2000)

[文献書誌] Oka A: "Expression of DNA-dependent protein kinase catalytic subunit and Ku80 in developing human brains : implication of DNA-repair in neurogenesis."Neuosci Lett. 292. 167-170 (2000)

[文献書誌] Shitoa M: "Cognitive and neurophysiological evaluation of Japanese dyslexia."Brain Dev. 22. 421-426 (2000)

[文献書誌] Yamamoto T: "Genotype-phenotype relationship of Niermann-Pick disease Type C : a possibility correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts."J Med Genet. 37. 707-711 (2000)

[文献書誌] Tsukamoto H: "SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick disease type C."Prenat Diagn. 21. 55-57 (2001)

[文献書誌] Yamamoto T: "DEFECT 11 syndrome associated with agenesis of the corpus callosum."J Med Genet.. 38. E5 (2001)

2000 年度実績報告書

難波栄二鳥取大学, 遺伝子実験施設, 助教授 (40237631)