VARIATION OF THE CGG REPEAT AT THE FRAGILE-X SITE RESULTS IN GENETIC INSTABILITY - RESOLUTION OF THE SHERMAN PARADOX
VARIATION OF THE CGG REPEAT AT THE FRAGILE-X SITE RESULTS IN GENETIC INSTABILITY - RESOLUTION OF THE SHERMAN PARADOX
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DOI：
10.1016/0092-8674(91)90283-5
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发表时间：
1991-12-20
期刊：
影响因子：
64.5
通讯作者：
CASKEY, CT
中科院分区：
文献类型：
--
作者：
FU, YH;KUHL, DPA;CASKEY, CT
脆性X综合征是由FMR-1基因编码序列中发现的（CGG）n重复序列突变引起的。在正常个体中，该区域的长度变异分析显示等位基因大小的范围从低的6个重复到高的54个重复。在脆性X染色体家族中没有表现出表型效应的前突变的大小范围从52到超过200个重复。所有大于52个重复的等位基因，包括在正常家族中鉴定的那些，都是减数分裂不稳定的，突变频率为1，而46个重复及以下的等位基因的75次减数分裂显示没有突变。前突变等位基因也是有丝分裂不稳定的，因为观察到嵌合现象。在卵子发生过程中，与智力迟钝相关的完全突变的扩展风险随着重复次数的增加而增加，这种风险的变化解释了谢尔曼悖论。
Fragile X syndrome results from mutations in a (CGG)n repeat found in the coding sequence of the FMR-1 gene. Analysis of length variation in this region in normal individuals shows a range of allele sizes varying from a low of 6 to a high of 54 repeats. Premutations showing no phenotypic effect in fragile X families range in size from 52 to over 200 repeats. All alleles with greater than 52 repeats, including those identified in a normal family, are meiotically unstable with a mutation frequency of one, while 75 meioses of alleles of 46 repeats and below have shown no mutation. Premutation alleles are also mitotically unstable as mosaicism is observed. The risk of expansion during oogenesis to the full mutation associated with mental retardation increases with the number of repeats, and this variation in risk accounts for the Sherman paradox.