Molecular biology of neurological diseases with abnormality of central or peripheral nerve myelin

中枢或周围神经髓磷脂异常的神经系统疾病的分子生物学

• 批准号: 07670720
• 负责人: NAKAGAWA Masanori
• 金额: $ 1.41万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670720/
• 关键词: Motor sensory neuropathy; Myelin; Hereditary; Linkage analysis; PLP; P_0; PMP22; Chromosome 3; 中枢性ミエリン; Po; 末梢神経障害; 優性遺伝; 劣性遺伝; P_0

Purpose :1. Gene mapping of neurological diseases with abnormality of central or peripheral nerve myelination using microsatellite polymorphic DNA markers.2. DNA sequencing of the families with neurological diseases linked to PLP, P0 or PMP22 gene locus.3. Linkage analysis of the families with no linkage to the known gene locus using 280 (CA) repeat microsatellite markers.4. Cloning of the genes mapped by the linkage analysis.Results :1. The gene responsible for a new type of motor and sensory neuropathy was mapped to chromosome 3 centromere region.2. In this region ; the patients'chromosomes showed an obvious increase in the allele frequency of five markers. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the presence of linkage disequilbrium and a common origin of this allele in all patients.3. Other familial disorders linked to P0 or PMP22 gene locus were analyzed by PCR-SSCP and DNA sequencing Linkage analysis of familial disorders with central or peripheral nerve abnormalities, which were not linked to PLP,P_0 and PMP22 gene loci, has been started. Conclusions : We identified a new type of hereditary motor and sensory neuropathy in this research project. Gene cloning responsible for this new disease is the important next research project.

目的：1.利用微卫星多态性DNA标记对中枢或周围神经髓鞘形成异常的神经系统疾病进行基因定位.与PLP、P0或PMP 22基因位点连锁的神经系统疾病家系的DNA测序.利用280个（CA）重复微卫星标记对与已知基因位点不连锁的家系进行连锁分析.克隆了连锁分析定位的基因。一种新型运动和感觉神经病的基因定位于3号染色体的着丝粒区域。在该区域，患者的染色体显示出五个标记的等位基因频率明显增加。D3 S1591中的一个等位基因在所有患者中是相同的，但在对照人群中的频率较低。这一发现表明所有患者存在连锁不平衡，该等位基因的起源相同.用PCR-SSCP和DNA测序方法分析与P0或PMP 22基因位点连锁的其他家族性疾病。对与PLP、P0和PMP 22基因位点无关的中枢或周围神经异常家族性疾病进行连锁分析。结论：我们在这项研究项目中发现了一种新的遗传性运动和感觉神经病。克隆导致这种新疾病的基因是下一个重要的研究项目。

项目成果

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