Methods for assessing DNA repair and repeat expansion in Huntington's Disease

Huntington’s disease (HD) is caused by a CAG repeat expansion in the HTT gene. Repeat length can change over time, both in individual cells and between generations, and longer repeats may drive pathology. Cellular DNA repair systems have long been implicated in CAG repeat instability but recent genetic evidence from humans linking DNA repair variants to HD onset and progression has reignited interest in this area. The DNA damage response plays an essential role in maintaining genome stability, but may also license repeat expansions in the context of HD. In this chapter we summarize the methods developed to assay CAG repeat expansion/contraction in vitro and in cells, and review the DNA repair genes tested in mouse models of HD. While none of these systems is currently ideal, new technologies, such as long-read DNA sequencing, should improve the sensitivity of assays to assess the effects of DNA repair pathways in HD. Improved assays will be essential precursors to high-throughput testing of small molecules that can alter specific steps in DNA repair pathways and perhaps ameliorate expansion or enhance contraction of the HTT CAG repeat

Chapter 10 - Safety Aspects

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Individual geographic mobility in a Viking-Age emporium—Burial practices and strontium isotope analyses of Ribe’s earliest inhabitants

Individual geographic mobility is a key social dynamic of early Viking-Age urbanization in Scandinavia. We present the first comprehensive geographic mobility study of Scandinavia’s earliest emporium, Ribe, which emerged around AD 700 in the North Sea region of Denmark. This article presents the results of strontium isotope analyses of 21 individuals buried at Ribe, combined with an in-depth study of the varied cultural affinities reflected by the burial practices. In order to investigate geographic mobility in early life/childhood, we sampled multiple teeth and/or petrous bone of individuals, which yielded a total of 43 strontium isotope analyses. Most individuals yielded strontium isotope values that fell within a relatively narrow range, between 87Sr/86Sr = 0.709 to 0.711. Only two individuals yielded values >87Sr/86Sr = 0.711. This suggests that most of these individuals had local origins but some had cultural affinities beyond present-day Denmark. Our results raise new questions concerning our understanding of the social and cultural dynamics behind the urbanization of Scandinavia