Molecular Basis of Maple Syrup Urine Disease
Molecular Basis of Maple Syrup Urine Disease
批准号:
01480553
负责人:
MATSUDA Ichiro
金额:
$1.28万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for General Scientific Research (B)
财政年份:
1989
资助国家:
日本
项目状态:
已结题
起止时间:
1989 至 1990
中文摘要
枫糖尿病(Maple sulphur urine disease,MSUD)是一种因支链α-酮酸脱氢酶复合物(BCKDH)E_1 α、E_1 β或E_2亚基缺乏而引起的常染色体隐性遗传病。我们进行了以下研究,以寻求MSUD的分子基础。我们分离并测序了BCKDH E_2亚基的cDNA插入片段。它由2,649个碱基对组成,开放阅读框为1,431个碱基对,可翻译成477个氨基酸,3 '非翻译区为1,205个碱基对。推测的氨基酸残基为硫辛酰结构域、E_3结合结构域和核心结构域.我们分析了人BCKDH E_1 β亚基的cDNA和基因组cDNA结构。该cDNA克隆含有4个核苷酸的5 '端非翻译序列、1.176个核苷酸的翻译序列和169个核苷酸的3'端非翻译序列。该cDNA编码342个氨基酸的亚基,Mr= 37,585,其包括50个氨基酸的前导序列。E_1 β亚基基因长度超过150 kb,分为10个外显子。所有的剪接供体和受体位点都符合GT/AG规则。转录起始位点位于起始密码子上游47个碱基处。在帽位点上游37个碱基和47个碱基处存在“CAAT”bax及其反向互补序列,但不存在“TATA”box样序列.我们发现了三种不同的突变基因:门诺MSUD的E_1 α亚基基因由T → A替换,日本MSUD家族的E_2亚基基因由78个碱基对的重复序列缺失。
英文摘要
Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder due to a deficiency of any subunits, E_1 alpha, E_1 beta or E_2 of branched chain alpha-ketoacid dehydrogenase complex (BCKDH). We performed following study to seek a molecular basis of the MSUD.1. We isolated and sequenced a cDNA insert of E_2 subunit of BCKDH. It consists of 2,649 base pairs with and open reading frame of 1,431 base pairs, which can be translated into 477 amino acids, and 3'-untranslated region of 1,205 base pairs. The deduced amino acid residues were a lipoyl-bearing domain, a E_3-binding domain and innor core domain.2. We analyzed cDNA and genomic cDNA structure of E_1beta subunit of human BCKDH. Isolated cDNA clone contained a 5'-untranslated sequence of 4 nucleotides, the translated sequence of 1.176 uncleotides and a 3'-untranslated sequence of 169 nucleotides. The cDNA encodes for a 342 amino acid subunit with a Mr=37,585, which includes a leader sequence of 50 amino acids. The gene of E_1beta subunit is over 150 kb long and splits into 10 exons. All of the splice donor and acceptor sites confirm to the GT/AG rule. The transcription initiation site was located 47 base upstream of the initiation codon. A "CAAT" bax and its reverse complement sequence were present at 37 bases and 47 bases upstream from the cap sites, but there was no "TATA" box like sequence.3. We found 3 different mutant genes ; A T-to-A substitution in the E_1alpha subunit gene in Mennonite MSUD, a deletion of an 11-base pair repeat sequence, which encodes a mitochondrial ratgetting leader peptide, in a Japanese MSUD family and a 78 base pair deletion in E_2 subunit genedue to splicing abnormalities in another Japanese MSUD family.
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Ichiro Matsuda: "A TーtoーA substitution in the E_1β subunit gene of the branchedーchain αーketoacid dehydrogenase complex in two cell lines derived from menonite maple syrup urine disease patients" Biochem.Biophy.Res.Comm.172. 646-651 (1990)
Ichiro Matsuda:“来自曼诺枫糖浆尿病患者的两种细胞系中支链 α-酮酸脱氢酶复合物的 E_1β 亚基基因中的 T 到 A 替换”Biochem.Biophy.Res.Comm.172。 - 651(1990)
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通讯作者:
Yoshitaka Nobukuni: "Maple syrup urine disease;Complete defect of the E_1β subunit of the branched chain αーketoacid dehydrogenase complex due to a deletion of an 11ーbase pair repeat sequence which encodes a mitochondrial targeting leader peptide in a fami
Yoshitaka Nobukuni:“枫糖浆尿病;由于家族中编码线粒体靶向前导肽的 11 碱基对重复序列缺失,导致支链 α-酮酸脱氢酶复合物的 E_1β 亚基完全缺陷。
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Hiroshi Mitsubuchi: "Maple syrup urine disease caused by a partial deletion in the inner E_2 core domain of the branched chain αーketo acid dehydrogenase complex due to aberrent splicing.A single base deletion at a 5′ーsplice donor site of an intron of the
Hiroshi Mitsubuchi:“枫糖浆尿病是由支链 α-酮酸脱氢酶复合物的内部 E_2 核心结构域由于剪接异常而部分缺失引起的。内含子 5 剪接供体位点的单碱基缺失这
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Hiroshi Mitsubuchi: "Structural organization and chromosomal localization of the gene for the E_1beta subunit of human branched chain alpha-keto acid dehydrogenase." J. Biol. Chem.
Hiroshi Mitsubuchi:“人支链 α-酮酸脱氢酶 E_1beta 亚基基因的结构组织和染色体定位。”
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Yoshitaka Nobukuni: "Maple syrup urine disease complete primary structure of the E_1beta subunit of human branched chain alpha-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease." J. Clin.
Yoshitaka Nobukuni:“枫糖浆尿病的人支链α-酮酸脱氢酶复合物的E_1β亚基的完整一级结构是从核苷酸序列和该疾病患者的基因分析中推导出来的。”
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共 23 条
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A Study on Video Coding Based on Combination of Motion Compensation and Waveform Coding
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依托单位:
Development and evoluation of viral and non-viral vectors for human gene therapy.
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财政年份:1995
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负责人:MATSUDA Ichiro
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Gene therapy of urea cycle deficirncy
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资助金额:$4.54万
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负责人:MATSUDA Ichiro
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依托单位:
海外基金