HAPLOTYPE ANALYSIS OF THE DELTA-2642 AND (CAG)(N) POLYMORPHISMS IN THE HUNTINGTONS-DISEASE (HD) GENE PROVIDES AN EXPLANATION FOR AN APPARENT FOUNDER HD HAPLOTYPE
HAPLOTYPE ANALYSIS OF THE DELTA-2642 AND (CAG)(N) POLYMORPHISMS IN THE HUNTINGTONS-DISEASE (HD) GENE PROVIDES AN EXPLANATION FOR AN APPARENT FOUNDER HD HAPLOTYPE
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DOI：
10.1093/hmg/4.2.203
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发表时间：
1995-02-01
影响因子：
3.5
通讯作者：
FERGUSONSMITH, MA
中科院分区：
文献类型：
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作者：
RUBINSZTEIN, DC;LEGGO, J;FERGUSONSMITH, MA
亨廷顿病(HD)基因内Delta2642缺失/插入多态的发现为探索HD的进化提供了工具，因为该缺失在正常染色体中很少见，但在HD染色体中存在过多。因此，Delta2642缺失等位基因被认为标志着特别容易变成HD染色体的正常染色体。我们在一系列人类和非人类灵长类动物种群中研究了这种多态。我们的结果表明，缺失事件可能发生在人类谱系中CAG等位基因长度在正常大小范围上端的染色体上，因为这种缺失似乎只与人类重复20或更多的染色体有关。这些缺失染色体很容易扩展到HD范围，因为它们处于正常范围的上端。这些数据解释了缺失所定义的明显的‘创立者’HD单倍型，并表明携带缺失的染色体并不比具有类似大小CAG重复的非缺失染色体更易变。
The discovery of the intragenic Delta 2642 deletion/insertion polymorphism in the Huntington's disease (HD) gene provides a tool to explore HD evolution, as the deletion is rare in normal chromosomes but overrepresented in HD chromosomes. Thus, Delta 2642 deletion alleles were thought to mark normal chromosomes that are particularly prone to becoming HD chromosomes. We have examined this polymorphism in a range of human and non-human primate populations. Our results suggest that the deletion event probably occurred in the human lineage on a chromosome with a CAG allele length at the upper end of the normal size range, as the deletion seemed to be only associated with human chromosomes with 20 or more repeats. These deletion chromosomes are prone to expansion into the HD range because they are at the upper end of the normal range. These data explain the apparent 'founder' HD haplotype defined by the deletion and suggest that chromosomes carrying the deletion are no more mutable than non-deletion chromosomes with similar sized CAG repeats.