Snell R G, MacMillan J C, Cheadle J P, Fenton I, Lazarou L P, Davies P, MacDonald M E, Gusella J F, Harper P S, Shaw D J
Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, UK.
Nat Genet. 1993 Aug;4(4):393-7. doi: 10.1038/ng0893-393.
The molecular analysis of a specific CAG repeat sequence in the Huntington's disease gene in 440 Huntington's disease patients and 360 normal controls reveals a range of 30-70 repeats in affected individuals and 9-34 in normals. We find significant negative correlations between the number of repeats on the HD chromosome and age at onset, regardless of sex of the transmitting parent, and between the number of repeats on the normal paternal allele and age at onset in individuals with maternally transmitted disease. This effect of the normal paternal allele may account for the weaker age at onset correlation between affected sib pairs with disease of maternal as opposed to paternal origin and suggests that normal gene function varies because of the size of the repeat in the normal range and a sex-specific modifying effect.
对440名亨廷顿舞蹈症患者和360名正常对照者的亨廷顿舞蹈症基因中特定CAG重复序列进行分子分析，结果显示，患病个体的重复序列范围为30至70次，正常个体为9至34次。我们发现，HD染色体上的重复序列数量与发病年龄之间存在显著负相关，这与传递亲本的性别无关；在母系遗传疾病个体中，正常父本等位基因上的重复序列数量与发病年龄之间也存在显著负相关。正常父本等位基因的这种作用可能解释了母系遗传而非父系遗传疾病的患病同胞对之间发病年龄相关性较弱的现象，这表明正常基因功能会因正常范围内重复序列的大小以及性别特异性修饰作用而有所不同。
