Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M
Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown 02129.
Nat Genet. 1993 Aug;4(4):387-92. doi: 10.1038/ng0893-387.
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.
亨廷顿舞蹈病基因中三核苷酸重复序列的扩展和不稳定最初被观察到，现在已在150个独立的亨廷顿舞蹈病家族中得到证实和扩展。亨廷顿舞蹈病（HD）染色体含有37 - 86个重复单位，而正常染色体显示有11 - 34个重复。HD重复序列长度与疾病发病年龄呈负相关。在超过80%的减数分裂传递中，HD重复序列是不稳定的，其大小既有增加也有减少，其中最大的增加发生在父系传递中。将精子发生作为重复序列不稳定的一个特殊来源，这一点在HD精子DNA的重复序列分布中得到体现。对这些家族成员中单个重复序列的长度和不稳定性进行分析，对症状前诊断具有深远意义。
