1994 Fiscal Year Annual Research Report

神経変性疾患の危険因子としてのミトコンドリア遺伝子変異の解明と変異蓄積機序

Research Project

Project/Area Number	06272210
Research Institution	Nagoya University
Principal Investigator	田中雅嗣名古屋大学, 医学部, 助教授 (60155166)
Keywords	ミトコンドリア遺伝子 / 塩基置換 / パーキンソン病 / 神経変性疾患 / 黒質線条体系 / 遺伝的危険因子 / ラジカル産生 / ラジカル脆弱性
Research Abstract	5例のパーキンソン病患者線条体からDNAを抽出し、mtDNAをPCR法を用いて増幅し、全塩基配列を決定した。翻訳領域において9個の非同義置換が見いだされた。症例1ではND2,Thr→Ala;ATP6,His→Tyr、症例2ではND6,Tyr→Cys、症例3ではND1,Ile→Val;ND2,Ile→Val、症例4ではND2,Thr→Ala;ND5,Thr→Ala、症例5ではND5,Thr→Ala;Cytb,Tyr→Hisが見られた。12SrRNA遺伝子において4箇所の塩基置換が見いだされた。症例1の663A→G置換はdomain Iのstem構造のA=U塩基対をG・U塩基対に変化させた。症例3の752C→T置換と1107T→C置換はloop領域にあり、1310C→T置換はstem構造のG≡C塩基対をG・U塩基対に変化させた。16SrRNA遺伝子において、症例1では、1736A→G置換、2151Aの挿入が観察された。tRNA遺伝子において、症例2ではtRNA^<Thr>のaminoacyl acceptor stemに15951A→G置換が観察された。この部位ではA=UまたはG≡C塩基対が幅広い種で保存されており、G・U塩基対は観察されなかった。この置換は肥大型心筋症の症例1例でも見られた。症例4ではtRNA^<Gln>のDHU loopに4386T→C置換が観察された。この置換は3例の他の症患コントロールでも見られた。これらのアミノ酸置換が、ミトコンドリアからのラジカルの産生を増加させる、あるいは遺伝子産物の酸化的損傷に対する脆弱性を高める可能性が考えられた。また、塩基置換がrRNAおよびtRNAに構造変化をもたらし、発症の遺伝的危険因子となる可能性が考えられた。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] M.M.Islam: "A complete cDNA sequence for core I protein subunit of human ubiquinol-cytochrome c reductase" Biochem.Mol.Biol.Int.32. 797-805 (1994)
[Publications] K.Katsumata: "Fragmentation of human heart mitochondrial DNA associated with premature aging" Biochem.Biophys.Res.Commun.202. 102-110 (1994)
[Publications] Y.Ota: "Early Retinal Involvement in Mitochondrial Myopathy with Mitochondrial DNA Delation" Retina.14. 270-276 (1994)
[Publications] M.Tanaka: "Strand asymmetry in human mitochondrial DNA mutations" Genomics. 22. 327-335 (1994)
[Publications] W.Sato: "Cardiomyopathy and Angiopathy in Patients with Mitochondrial Myopathy,Lactiv Acidosis and Stroke-like Episodes" Am.Heart J.128. 733-741 (1994)
[Publications] M.Hayakawa: "Fragmentation of human heart mitochondrial DNA associated with premature aging" J.Mol.Cell.Cardiol.26. CCXXI (1994)
[Publications] Sergei.A.Kovalenko: "A common hot spot for somatic and germline mutations in rat mitochondrial DNA:Analysis by fluorescence-based sscp" Biochem.Mol.Biol.Int.34. 1205-1214 (1994)
[Publications] T.Furui: "Decrease in Cytochrome c Oxidase and Cytochrome Oxidase Subunit I Messenger Ribonucleic Acid Levels in Preeclamptic Pregnancies" Obstet.Gynecol.84. 283-288 (1994)
[Publications] S.A.Kovalenco: "Simple methods for preparation of plasmid DNA yielding long and accurate sequence data" Nucleic Acids Research. 22. 5771-5772 (1994)
[Publications] T.Ozawa: "Mitochondrial DNA mutations and survival rate" Lancet. 345. 189 (1995)
[Publications] S.Ikebe: "Point Mutations of Mitochondrial Genome in Parkinson's Disease" Mol.Brain.Res.28. 281-295 (1995)
[Publications] M.Tanaka: "Mitochondrial DNA mutations in cardiomyopathy:combination of replacements yielding cysteine residues and tRNA mutations" Muscle and Nerve. (in press). (1995)
[Publications] T.Ozawa: "Genotype and phenotype of a severe mitochondrial cardiomyopathy:a recipient of heart transplantation and the genetic control" Biochem.Biophys.Res.Commun.(accepted). (1995)

1994 Fiscal Year Annual Research Report

神経変性疾患の危険因子としてのミトコンドリア遺伝子変異の解明と変異蓄積機序

Principal Investigator

田中 雅嗣 名古屋大学, 医学部, 助教授 (60155166)

Research Products

[Publications] M.M.Islam: "A complete cDNA sequence for core I protein subunit of human ubiquinol-cytochrome c reductase" Biochem.Mol.Biol.Int.32. 797-805 (1994)

[Publications] K.Katsumata: "Fragmentation of human heart mitochondrial DNA associated with premature aging" Biochem.Biophys.Res.Commun.202. 102-110 (1994)

[Publications] Y.Ota: "Early Retinal Involvement in Mitochondrial Myopathy with Mitochondrial DNA Delation" Retina.14. 270-276 (1994)

[Publications] M.Tanaka: "Strand asymmetry in human mitochondrial DNA mutations" Genomics. 22. 327-335 (1994)

[Publications] W.Sato: "Cardiomyopathy and Angiopathy in Patients with Mitochondrial Myopathy,Lactiv Acidosis and Stroke-like Episodes" Am.Heart J.128. 733-741 (1994)

[Publications] M.Hayakawa: "Fragmentation of human heart mitochondrial DNA associated with premature aging" J.Mol.Cell.Cardiol.26. CCXXI (1994)

[Publications] Sergei.A.Kovalenko: "A common hot spot for somatic and germline mutations in rat mitochondrial DNA:Analysis by fluorescence-based sscp" Biochem.Mol.Biol.Int.34. 1205-1214 (1994)

[Publications] T.Furui: "Decrease in Cytochrome c Oxidase and Cytochrome Oxidase Subunit I Messenger Ribonucleic Acid Levels in Preeclamptic Pregnancies" Obstet.Gynecol.84. 283-288 (1994)

[Publications] S.A.Kovalenco: "Simple methods for preparation of plasmid DNA yielding long and accurate sequence data" Nucleic Acids Research. 22. 5771-5772 (1994)

[Publications] T.Ozawa: "Mitochondrial DNA mutations and survival rate" Lancet. 345. 189 (1995)

[Publications] S.Ikebe: "Point Mutations of Mitochondrial Genome in Parkinson's Disease" Mol.Brain.Res.28. 281-295 (1995)

[Publications] M.Tanaka: "Mitochondrial DNA mutations in cardiomyopathy:combination of replacements yielding cysteine residues and tRNA mutations" Muscle and Nerve. (in press). (1995)

[Publications] T.Ozawa: "Genotype and phenotype of a severe mitochondrial cardiomyopathy:a recipient of heart transplantation and the genetic control" Biochem.Biophys.Res.Commun.(accepted). (1995)

田中雅嗣名古屋大学, 医学部, 助教授 (60155166)