2000 Fiscal Year Annual Research Report

小児自閉症の遺伝要因を解明するDNAチップの開発

Research Project

Project/Area Number	12670752
Research Institution	Tottori University
Principal Investigator	難波栄二鳥取大学, 遺伝子実験施設, 助教授 (40237631)
Keywords	自閉症 / セロトニン受容体遺伝子 / SNPs / 関連遺伝子解析 / HTR1A
Research Abstract	【目的】私は小児の脳障害の遺伝的要因を明らかにするために、様々な疾患の遺伝研究を進めている。本研究では主に、自閉症の遺伝的背景を明らかにするために、セロトニン関連遺伝子に注目し検討を行った。【方法】10のセロトニン受容体遺伝子から20のSingle nucleotide polymorphisms(SNPs)候補領域を選択して検討した。SNPsの候補領域としては米国NIHのNCBIならびに日本のSNPsホームページ上に公開されている情報をもとに選択した。セロトニン関連遺伝子としては、5-hydroxytryptamin receptor(HTR)からHTR1A(4)、HTR1B(3),HTR1E(2)、HTR1D(1),HTR1F(1),HTR2A(3),HTR3A(1),HTR5A(2),HTR2C(1),HTR6(2)の遺伝子からカッコ内の数のSNPsを選択し、SSCP法と塩基配列決定法にて解析した。この解析には鳥取大学および東京大学倫理委員会の承認の上、その手続きに従ってインフォームドコンセントを得た自閉症患者57名と正常対照100名のDNA検体を用いた。【結果】まず正常対照20検体、患者20検体を解析したところ、23の候補領域のうち5のSNPs(HTR1Aの2つ、HTR1B、HTR1D.HTR6のそれぞれ1つ)で多型を認めたが、他の18の領域では多型は認められなかった。この5SNPsを用いて関連遺伝子解析を行った結果、HTR1A遺伝子では1つのSNPsがχ^2=5.30、P=0.021、もうひとつがχ^2=6.44、P=0.011、と統計学的に有意な結果が得られた。他の3つのSNPsではいずれも有意な関連はなかった。【結論】HTR1A遺伝子は自閉症に関連している可能性が示された。

Research Products

(11 results)

All Other

All Publications (11 results)

[Publications] Kato M: "Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly."Ann Neurol. 47. 514-516 (2000)
[Publications] 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)
[Publications] Ikebuchi M: "The Arg1075 His substitution in the FBN1 gene is clinically innocent for Marfan syndrome."Hum Mut. 15. 298-298 (2000)
[Publications] Chikumi H: "Fibrillin gene (FBN1) mutations in Japanese patients with Marfan syndrome."J Hum Genet. 45. 115-118 (2000)
[Publications] Nagata K: "A novel interstitial deletion of KAL1 in a Japanese family with Kallmann syndrome."J Hum Genet. 45. 237-240 (2000)
[Publications] Pipo JR: "Two novel serine repeat length polymorphisms (1043insS and 1043insSS) at exon 23 of the TSC1 gene."Hum Mut. 16. 375-375 (2000)
[Publications] Saito Y: "Widespread expression of α-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protracted clinical course."J Neurol Sci. 177. 48-59 (2000)
[Publications] Tanaka Y: "Congenital myotonic dystrophy : report of paternal transmission."Brain Dev. 22. 132-134 (2000)
[Publications] Yamamoto T: "Genotype-phenotype relationship of Niemann-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)
[Publications] Tsukamoto H: "SSCP analysis by RT-PCR for the prenatal diagnosis of Niemann-Pick disease type C."Prenat Diagn. 21. 55-57 (2001)
[Publications] Yamamoto T: "DEFECT 11 syndrome associated with agenesis of the corpus callosum."J Med Genet.. 38. E5-E5 (2001)

2000 Fiscal Year Annual Research Report

小児自閉症の遺伝要因を解明するDNAチップの開発

Principal Investigator

難波 栄二 鳥取大学, 遺伝子実験施設, 助教授 (40237631)

Research Products

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

[Publications] 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)

[Publications] Ikebuchi M: "The Arg1075 His substitution in the FBN1 gene is clinically innocent for Marfan syndrome."Hum Mut. 15. 298-298 (2000)

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

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

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

[Publications] Saito Y: "Widespread expression of α-synuclein and tau immunoreactivity in Hallervorden-Spatz syndrome with protracted clinical course."J Neurol Sci. 177. 48-59 (2000)

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

[Publications] Yamamoto T: "Genotype-phenotype relationship of Niemann-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)

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

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

難波栄二鳥取大学, 遺伝子実験施設, 助教授 (40237631)