CRYPTIC AND POLAR VARIATION OF THE FRAGILE-X REPEAT COULD RESULT IN PREDISPOSING NORMAL ALLELES
CRYPTIC AND POLAR VARIATION OF THE FRAGILE-X REPEAT COULD RESULT IN PREDISPOSING NORMAL ALLELES
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DOI：
10.1016/0092-8674(94)90134-1
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发表时间：
1994-06-17
期刊：
影响因子：
64.5
通讯作者：
WARREN, ST
中科院分区：
文献类型：
--
作者：
KUNST, CB;WARREN, ST
脆性X综合征是由CGG重复序列的扩增引起的，该重复序列通常被偶尔的AGG三联体打断。连锁不平衡表明，某些正常的单倍型可能有助于不平等的池脆弱的X染色体。正常等位基因的序列分析表明重复的隐蔽性的单倍型特异性变化。变异主要发生在重复序列的3'端，表明DNA复制的前导链和滞后链之间的稳定性差异。具有大于24个完美3' CGG重复的正常等位基因更频繁地出现在脆性X染色体中过度代表的单倍型上。这样的等位基因在2%的正常染色体中发现，并且可能构成脆性X染色体所衍生的祖先等位基因库。这些数据也可能意味着某些易感等位基因和脆性X染色体扩增之间的平衡尚未达到，表明该基因座正在发生进化变化。
Fragile X syndrome results from the expansion of a CGG repeat that is normally interrupted by occasional AGG triplets. Linkage disequilibrium suggests that certain normal haplotypes may contribute unequally to the pool of fragile X chromosomes. Sequence analysis of normal alleles demonstrates haplotype-specific variation of the cryptic nature of the repeat. Variation occurs principally at the 3' end of the repeat, suggesting stability differences between the leading and lagging strands of DNA replication. Normal alleles with greater than 24 perfect 3' CGG repeats appear more frequently on haplotypes overrepresented among fragile X chromosomes. Such alleles are found in 2% of normal chromosomes and could comprise the ancestral allelic pool from which fragile X chromosomes are derived. These data also may imply that equilibrium between certain predisposed alleles and fragile X expansions has not yet been attained, indicating ongoing evolutionary change at this locus.