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Abstract：
The polymorphic trinucleotide repetitive region in the FMR1 gene 5\'UTR contains AGG interspersions, particularly in normal-sized alleles (CGG < 45). In this range repetitive stretches are typically interrupted once or twice, although alleles without or with three or more AGG interspersions can also be observed. AGG interspersions together with the total length of the repetitive region confer stability and hinder expansion to pathogenic ranges: either premutation (55 < CGG < 200) or full mutation (CGG > 200). The AGG interspersions have long been identified as one of the most important features of FMR1 repeat stability, being particularly important to determine expansion risk estimates in female premutation carriers. We sought to compute the combined AGG interspersion numbers and patterns, aiming to define FMR1 repetitive tract complexity combinations. A mathematical model, the first to compute this cumulative effect, was developed and validated using data from 131 young and healthy females. Plotting of their allelic complexity enabled the identification of two statistically distinct groups - equivalent and dissimilar allelic combinations. The outcome, a numerical parameter designated allelic score, depicts the repeat substructure of each allele, measuring the allelic complexity of the FMR1 gene including the AGGs burden, thus allowing new behavioral scrutiny of normal-sized alleles in females.
摘要：
FMR1基因5'UTR中的多态三核苷酸重复区包含AGG穿插，特别是在正常大小的等位基因中（CGG<45）。在此范围内，重复拉伸通常会中断一次或两次，尽管也可以观察到没有或具有三个或更多个AGG穿插的等位基因。AGG穿插与重复区的总长度一起赋予稳定性并阻碍扩展到致病范围:前突变(55200)。AGG的散布早已被认定为FMR1重复稳固性的最重要特征之一，对于确定女性前突变携带者的扩展风险估计尤为重要。我们试图计算组合的AGG穿插数量和模式，旨在定义FMR1重复道复杂性组合。一个数学模型,第一个计算这种累积效应的人，使用来自131名年轻健康女性的数据进行开发和验证。对其等位基因复杂性的作图能够鉴定两个统计学上不同的组-等效和不相似的等位基因组合。结果,指定等位基因得分的数值参数，描绘了每个等位基因的重复亚结构，测量FMR1基因的等位基因复杂性，包括AGGs负担，从而允许对女性正常大小的等位基因进行新的行为审查。
