TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE
TRINUCLEOTIDE REPEAT LENGTH INSTABILITY AND AGE-OF-ONSET IN HUNTINGTONS-DISEASE
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DOI：
10.1038/ng0893-387
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发表时间：
1993-08-01
期刊：
影响因子：
30.8
通讯作者：
MACDONALD, M
中科院分区：
文献类型：
--
作者：
DUYAO, M;AMBROSE, C;MACDONALD, M
最初在亨廷顿病基因中观察到的一个扩展的和不稳定的三核苷酸重复序列现在已经在150个独立的亨廷顿病家族中得到证实和扩展。HD染色体包含37 - 86个重复单位，而正常染色体显示11 - 34个重复单位。HD重复序列长度与发病年龄呈负相关。HD重复是不稳定的，在80%以上的减数分裂传输显示增加和减少的大小与最大的增加发生在父系传输。精子发生作为重复不稳定性的特定来源的靶向反映在HD精子DNA的重复分布中。这些家庭的成员中的个体重复序列的长度和不稳定性的分析具有深刻的影响症状前诊断。
The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.