Nuclear organization of expanded trinucleotide repeats

Expanded trinucleotide repeats (TNRs) are the underlying cause of at least twenty neurological and neuromuscular disorders including myotonic dystrophy type 1 and Huntington’s disease. Expansions occur when the TNR tract exceeds stable lengths. Upon repeat expansion, certain genes acquire heterochromatic characteristics. This raises the question of whether repeat expansion causes changes in the 3D organization of expanded TNR loci. Therefore, the aim of this thesis is to systematically analyze the higher-order chromatin structure of expanded CTG/CAG repeat loci. To do this, we use a combination of conformation capture techniques (e.g. 4C-seq), next-generation sequencing, and bioinformatic data analysis approaches.