Stool is a sensitive and noninvasive source of DNA for monitoring expansion in repeat expansion disease mouse models

Repeat expansion diseases (REDs) are a large group of human genetic disorders caused by expansion of a specific short tandem repeat sequence. Expansion in somatic cells affects age at onset and disease severity in some of these disorders. However, alleles in blood, a commonly used source of DNA, usually show much less expansion than disease-relevant cells in the central nervous system (CNS) 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 (FXDs), Huntington's disease (HD), Spinocerebellar ataxia type 1 (SCA1) and Spinocerebellar ataxia type 2 (SCA2). We found that stool is a much better indicator of somatic expansion than blood. Since stool is a sensitive and non-invasive source of DNA, it may be useful for studies of factors affecting expansion risk or the monitoring of treatments aimed at reducing expansion in preclinical trials since it would allow expansions to be examined longitudinally in the same animal and allow significant effects to be ascertained much earlier than is possible with other DNA sources.