Analysis of the qene for Machado-Joseph disease

马查多-约瑟夫病(MJD)是日本最常见的常染色体显性遗传脊髓小脑变性类型之一。通过系统遗传连锁分析，利用高度多态的微卫星DNA标记，将MJD的基因座定位在染色体14q(14q24.3-32.1)的长臂上。在葡萄牙血统中发现的MJD也与相同的DNA标记紧密连锁。京都大学的研究人员从cDNA文库中鉴定出MJD基因MJD1在中枢神经系统中表达，并显示CAG重复序列异常扩张。我们证实了这一结果，并表明MJD1基因CAG重复数与遗传预期、父系偏见和日本MJD的临床表型有关。

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.