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。 2．对PLP、P0或PMP22基因位点相关神经系统疾病家系进行DNA测序。 3．使用280（CA）重复微卫星标记对与已知基因位点无连锁的家族进行连锁分析。4．通过连锁分析对基因进行克隆。结果： 1．负责新型运动和感觉神经病的基因定位于3号染色体着丝粒区域。2．在这个地区；患者染色体显示5个标记的等位基因频率明显增加。 D3S1591 中的一个等位基因在所有患者中都是相同的，但在对照人群中出现频率较低。这一发现表明所有患者中都存在连锁不平衡以及该等位基因的共同起源。3．通过PCR-SSCP和DNA测序分析与P0或PMP22基因位点相关的其他家族性疾病与中枢或周围神经异常的家族性疾病与PLP、P_0和PMP22基因位点无关的连锁分析已经开始。结论：我们在本研究项目中发现了一种新型遗传性运动和感觉神经病。负责这种新疾病的基因克隆是下一个重要的研究项目。

项目成果

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