RELATIONSHIP BETWEEN TRINUCLEOTIDE REPEAT EXPANSION AND PHENOTYPIC VARIATION IN HUNTINGTONS-DISEASE
RELATIONSHIP BETWEEN TRINUCLEOTIDE REPEAT EXPANSION AND PHENOTYPIC VARIATION IN HUNTINGTONS-DISEASE
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DOI：
10.1038/ng0893-393
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发表时间：
1993-08-01
期刊：
影响因子：
30.8
通讯作者：
SHAW, DJ
中科院分区：
文献类型：
--
作者：
SNELL, RG;MACMILLAN, JC;SHAW, DJ
对440名亨廷顿病患者和360名正常对照者中的亨廷顿病基因中的特定CAG重复序列的分子分析揭示了在患病个体中的30-70个重复序列和在正常人中的9-34个重复序列的范围。我们发现显着的负相关HD染色体上的重复数和发病时的年龄，无论性别的传递父母，和之间的重复数正常的父亲等位基因和发病时的年龄在个体与母系传播疾病。这种影响的正常父亲等位基因可能占发病年龄较弱的相关性受影响的同胞对与疾病的母亲，而不是父亲的起源，并表明，正常的基因功能不同，因为在正常范围内的重复序列的大小和性别特异性的修改效果。
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.