HAPLOTYPE ANALYSIS AT THE FRAXA LOCUS IN THE JAPANESE POPULATION
HAPLOTYPE ANALYSIS AT THE FRAXA LOCUS IN THE JAPANESE POPULATION
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DOI：
10.1002/ajmg.1320510422
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发表时间：
1994-07-15
期刊：
影响因子：
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通讯作者：
HORI, T
中科院分区：
文献类型：
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作者：
RICHARDS, RJ;KONDO, I;HORI, T
脆性X综合征是人类最常见的遗传性疾病之一，其特征在于FRAXA基因座上一个可遗传的不稳定DNA序列p（CCG）n重复序列的动态突变。最近有人提出，一些创始人染色体是负责大多数脆弱的X突变在高加索人口。为了研究日本人群中脆性X突变的起源，我们分析了日本男性中40条无关脆性X染色体和142条正常X染色体中FRAXA基因座的单倍型，使用两个多态性AC重复序列FRAXAC 1和FRAXAC 2，它们位于脆性位点的侧翼。这项分析为日本人群中的创始人脆性X染色体提供了证据，与高加索人相似，尽管涉及不同的单倍型。日本人群中X染色体中p（CCG）n重复序列的正常等位基因大小的分布与高加索人的报告非常相似，除了最常见的拷贝数（n = 28）比高加索人少一个拷贝，并且在35个拷贝处有一个额外的峰值。FRAXAC等位基因与非脆性X染色体p（CCG）n重复拷贝数之间存在显著相关性，但p（CCG）n重复拷贝数大于31的等位基因与脆性X常见FRAXAC单倍型之间不存在分离。(C)1994 Wiley-Liss，Inc.
Fragile X syndrome, one of the most common human genetic diseases, is characterized by a unique genetic mechanism which involves dynamic mutation in a heritable unstable DNA sequence, a p(CCG)n repeat, in the FRAXA locus. It has recently been suggested that a few founder chromosomes are responsible for most fragile X mutations in the Caucasian population. In order to investigate the origin of the fragile X mutations in the Japanese population, we analyzed haplotypes of the FRAXA locus in 40 unrelated fragile X chromosomes and 142 normal X chromosomes in Japanese males, by using two polymorphic AC repeats, FRAXAC1 and FRAXAC2, which flank the fragile site. This analysis provided evidence for founder fragile X chromosomes in the Japanese population, similar to that in Caucasians, although different haplotypes are involved. The distribution of normal allele size of the p(CCG)n repeat among the X chromosomes in the Japanese population is very similar to that reported for Caucasians, except that the most frequent copy number (n = 28) is one copy less than that in Caucasians and that there is an additional peak at 35 copies. There is significant correlation between FRAXAC alleles and the p(CCG)n repeat copy number in non-fragile X chromosomes, however, alleles with more than 31 copies of the p(CCG)n repeat do not segregate with either of the fragile X common FRAXAC haplotypes. (C) 1994 Wiley-Liss, Inc.