Abstract：
Repeat expansion diseases are a large group of human genetic disorders caused by expansion of a specific short tandem repeat tract. Expansion in somatic cells affects age of onset and disease severity in some of these disorders. However, alleles in DNA derived from blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system in both humans and mouse models. Here we examined the extent of expansion in different DNA sources from mouse models of the fragile X-related disorders, Huntington\'s disease, spinocerebellar ataxia type 1 and spinocerebellar ataxia type 2. We found that DNA isolated from stool is a much better indicator of somatic expansion than DNA from blood. As stool is a sensitive and noninvasive source of DNA, it can be useful for studies of factors affecting the risk of expansion, or the monitoring of treatments aimed at reducing expansion in preclinical trials, as it would allow expansions to be examined longitudinally in the same animal and allow significant changes in expansion to be observed much earlier than is possible with other DNA sources.
摘要：
重复扩增疾病是由特定的短串联重复序列扩增引起的一大组人类遗传疾病。在这些疾病中的一些中,体细胞的扩增影响发病年龄和疾病严重程度。然而,来自血液的DNA中的等位基因，常用的DNA来源，在人类和小鼠模型中，通常显示出比中枢神经系统中疾病相关细胞少得多的扩增。在这里，我们检查了来自脆性X相关疾病的小鼠模型的不同DNA来源的扩增程度，亨廷顿病,脊髓小脑共济失调1型和脊髓小脑共济失调2型。我们发现从粪便中分离的DNA比血液中的DNA更好地指示体细胞扩增。因为粪便是一种敏感的非侵入性DNA来源，它可以用于研究影响扩张风险的因素，或监测旨在减少临床前试验扩展的治疗方法，因为这将允许在同一只动物中纵向检查扩增，并允许比其他DNA来源更早地观察到扩增的显着变化。
