Analysis of the qene for Machado-Joseph disease

马查多-约瑟夫病的基因分析

• 批准号: 05454261
• 负责人: NISHIZAWA Masatoyo
• 金额: $ 4.48万
• 依托单位: Jichi Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454261/
• 关键词: Machado-Joseph disease; chromosome 14; molecular genetics; triplet repeat; anticipation; gene analysis; Machado-Joseph病; triplet repeat; 脊髄小脳変性症; 連鎖解析; 遺伝子座

Machado-Joseph disease (MJD) is one of the most common forms of spinocerebellar degeneration with autosomal dominant inheritance in Japan. We mapped the gene locus for MJD to the long arm of chromosome 14q (14q24.3-32.1) by systematic genetic linkage analysis using highly polymorphic microsatellite DNA markers. MJD found in Portuguese-Azorean descent was also tightly linked to the same DNA markers.The gene for MJD,MJD1, was identified from cDNA libraries as the one expressed in the CNS and showing abnormal expansion of CAG repeat by researchers in Kyoto University. We confirmed thier result and showed that the number of CAG repeat in MJD1 gene is associated with genetic anticipation, paternal bias, and the clinical phenotypes of Japanese MJD.

Machado-Joseph病（MJD）是日本最常见的常染色体显性遗传脊髓小脑变性疾病之一。利用高度多态性的微卫星DNA标记，通过系统遗传连锁分析，将MJD基因定位于染色体14 q长臂（14q24.3-32.1）。在葡萄牙-亚速尔群岛血统中发现的MJD也与相同的DNA标记紧密相连。京都大学的研究人员从cDNA文库中鉴定出MJD的基因MJD 1，该基因在CNS中表达，并显示CAG重复序列的异常扩增。我们证实了他们的结果，并表明MJD 1基因CAG重复序列的数量与遗传预测，父亲的偏见，日本MJD的临床表型。

项目成果

西澤、正豊: "Machado-Joseph病遺伝子座の連鎖解析" 医学のあゆみ. 167. 639-

Nishizawa, Masatoyo：“Machado-Joseph 病位点的连锁分析”《医学史》167. 639-

Sequeiros J,et al.: "Genetic likage studies of Machado-Joseph disease with chromosome 14q STRPs in 16 Portuguese-Azorean kindreds." Genomics. 21. 645-648 (1994)

Sequeiros J 等人：“在 16 个葡萄牙-亚速尔群岛亲属中对马查多-约瑟夫病与染色体 14q STRP 的遗传相似性研究。”

Takiyama T: "A clinical and pathological study of a large Japanese family with Machado-Joseph disease tightly linked to the DNA markers on chromosome 14q" Neurology. 44(in press). (1994)

Takiyama T：“对一个患有 Machado-Joseph 病的日本大家族进行的一项临床和病理学研究，该家族与染色体 14q 上的 DNA 标记紧密相关”。

Sequeiros J,et al.: "Genetic linkage studies of Machado-Joseph disease with chromosome 14a STRPs in 16 Portuguese-Azoroan kindreds." Genomics. 21. 645-648 (1994)

Sequeiros J 等人：“马查多-约瑟夫病与 16 个葡萄牙-阿速罗人亲属中 14a 号染色体 STRP 的遗传连锁研究。”

Takiyama Y,et al: "A clinical and pathologic study of a large Japanese family with Machado-Joseph disease tightly linked to the DNA markers on chromosome 14q." Neurology. 44. 1302-1308 (1994)

Takiyama Y 等人：“对患有 Machado-Joseph 病的一个日本大家族进行的临床和病理学研究，该家族与 14q 染色体上的 DNA 标记紧密相关。”