• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular Genetic Study on Adrenoleukodystrophy

Research Project

Project/Area Number 01440042
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNiigata University

Principal Investigator

MIYATAKE Tadashi  Niigata University Brain Research Institute Professor Department of Neurology, 脳研究所, 教授 (50048998)

Co-Investigator(Kenkyū-buntansha) OHNO Tsukasa  Brain Research Institute Assistant Department of Neurology, 脳研究所, 助手 (50213814)
TSUJI Shoji  Niigata University Hospital Assistant Department of Neurology, 医学部附属病院, 助手 (70150612)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥20,200,000 (Direct Cost: ¥20,200,000)
Fiscal Year 1990: ¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1989: ¥13,100,000 (Direct Cost: ¥13,100,000)
KeywordsAdrenoleukodystrophy / Reverse Genetics / Linking Clone / CpG Island / Transcribed Sequences / Color Pigment Gene / Human X Chromosome / Very Long Chain Fatty Acid / reverse genetics / linking clone / CpG island / transcribed sequences / ヒトX染色体 / 副腎白質ジストロフィ- / X染色体 / 連鎖解析 / リバ-ス・ジェネティックス / メッセンジャ-RNA / cDNAライブラリ- / パルスフィ-ルド電気泳動 / DNAマ-カ-
Research Abstract

Adrenoleukodystrophy (ALD) is an X-linked recessive neurologic disease. Previous linkage studies have indicated that the ALD gene is tightly linked to Xq28 markers including G6PD and St14. To identify the ALD gene by "reverse genetics" approach, we have developed the following strategies. First, we have constructed a cosmid genomic library from a somatic cell hybrid, X3000-11, carrying only a part of human X chromosome (Xq24-28) as the human chromosome. We have isolated 1,778 human Xq24-28 cosmid clones and prepared DNA from all the cosmid clones.
We have identified 400 NotI linking clones and 350 clones carrying CpG islands, which should facilitate the identification of all house keeping genes as well as some tissue specific genes.
To efficiently identify messenger RNA transcribed from Xq24-28, we have constructed a hncDNA (heterogenous nuclear RNA-derived cDNA) library from the X3000-11 utilizing primers specific for spliceーsites. We have identified 534 hncDNA clones and confirmed that all hncDNA clones characterized are derived from Xq24-28 region.
Previous findings that color blindness is frequently found in ALD, suggests that the ALD gene might be very close to the color pigment gene. We have developed ALD cell bank and analyzed genomic DNA of 13 ALD patients. We have found a total deletion of green pigment gene in an ALD patient, which has not been described. If the ALD gene and the green pigment gene are simultaneously deleted, the case might facilitate the identification of the ALD gene.
To develop new therapeutic strategy to lower very long chain fatty acids, we have developed a new assay for evaluation of metabolic inhibitors. We have found that monoーunsaturated fatty acids with carbon numbers 20 and 22 lower the very long chain fatty acids than oleic acid.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Ryoko Koike: "Physiological significance of fatty acid elongation system in adrenoleukodystrophy." J.Neurol.Sci.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Rui Kondo: "Identification of a mutation in arylsulfatase A gene of a patient with adult type metachromatic leukodystrophy." Amer.J.Hum.Genet.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hajime Tanaka: "Linkage analysis of juvenile parkinsonism to tyrosine hydroxylase gene locus on chromosome ll." Neurology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hisashi Kobayashi: "Stability of messenger RNA in postmortem human brains and construction of human brain cDNA libraries." J.Mol.Neurosci.2. 29-34 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Makoto Yoneda: "A common mitochondrial DNA mutation in the tーRNAAALysBB of patients with myoclonus epilepsy associated with raggedーred fibers." Biochem.Int.21. 789-796 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Toyoaki Yamauchi: "Molecular cloning of two species of cDNAs for human αーNー acetylgalactosaminidase and expression in mammalian cells." Biochem.Biophys.Res.Commun.170. 231-237 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Shoji Tsuji: "Molecular cloning of a fullーlength cDNA for human αーNー acetylgalactosaminidase(αーgalactosidase B)." Biochem.Biophys.Res.Commun.163. 1498-1504 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Makoto Yoneda: "Mitochondrial mutation in family with Leber´s hereditary optic neuropathy." Lancet. 1. 1076-1077 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ryoko Koike: "Physiological significance of fatty acid elongation system adrenoleukodystrophy." J. Neurol. Sci.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Rui Kondo: "Identification of a mutation in arylsulfatase a gene of a patient with adult type metachromatic leukodystrophy." Amer. J. Hum. Genet.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hajime Tanaka: "Linkage analysis of juvenile parkinsonism to tyrosine hydroxylase gene locus on chromosome 11." Neurology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Hisashi Kobayashi: "Stabelity of messenger RNA in postmortem human brains and construction of human brain cDNA libraries." J. Mol. Neurosci.2. 29-34 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Makoto Yoneda: "A common mitochondrial DNA mutation in the tーRNA^<Lys> of patients with myoclonus epilepsy associated with raggedred fibers." Biochem. Int. 21. 789-796 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Toyoaki Yamauchi: "Molecular cloning of two species of cDNAs for human alphaーNacetylgalactosaminidase and expression in mammalian cells." Biochem. Biophys. Res. Commun.170. 231-237 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Shoji Tsuji: "Molecular cloning of a fullーlength cDNA for human alphaーNacetylgalactosaminidase (alpha-galactosidase B)." Biochem. Biophys. Res. Commun.163. 1498-1504 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Makoto Yoneda: "Mitochondrial mutation in family with Leber's hereditary optic neuropathy." Lancet. 1. 1076-1077 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Ryoko Koike: "Physiological significance of fatty acid elongation system in adrenoleukodystrophy." J.Neurol.Sci.

    • Related Report
      1990 Annual Research Report
  • [Publications] Rui Kondo: "Identification of a mutation in arylsulfatase A gene of a patient with adult type metachromatic leukodystrophy." Amer.J.Hum.Genet.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hajime Tanaka: "Linkage analysis of juvenile parkinsonism to tyrosine hydroxylase gene locus on chromosome ll." Neurology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hisashi Kobayashi: "Stability of messenger RNA in postmortem human brains and construction of human brain cDNA libraries." J.Mol.Neurosci.2. 29-34 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Makoto Yoneda: "A common mitochondrial DNA mutation in the tーRNA^<Lys> of patients with myoclonus epilepsy associated with raggedーred fibers." Biochem.Int.21. 789-796 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Toyoaki Yamauchi: "Molecular cloning of two species of cDNAs for human αーNーacetylgalactosaminidase and expression in mammalian cells." Biochem.Biophys.Res.Commun.170. 231-237 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Shoji Tsuji: "Molecular cloning of a fullーlength cDNA for human αーNーacetylgalactosaminidase (αーgalactosidase B)." Biochem.Biophys.Res.Commun.163. 1498-1504 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Makoto Yoneda: "Mitochondrial mutation in family with Leber's hereditary optic neuropathy." Lancet. 1. 1076-1077 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hisashi.Kobayashi: "Stability of messenger RNA in postーmortem human brains and construction of human brain cDNA libraries." J.Mol.Neurosci.

    • Related Report
      1989 Annual Research Report

URL: 

Published: 1989-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi