Profiling human pathogenic repeat expansion regions by synergistic and multi-level impacts on molecular connections.

ABSTRACT: Whilst DNA repeat expansions cause numerous heritable human disorders, their origins and underlying pathological mechanisms are often unclear. We collated a dataset comprising 224 human repeat expansions encompassing 203 different genes, and performed a systematic analysis with respect to key topological features at the DNA, RNA and protein levels. Comparison with controls without known pathogenicity and genomic regions lacking repeats, allowed the construction of the first tool to discriminate repeat regions harboring pathogenic repeat expansions (DPREx). At the DNA level, pathogenic repeat expansions exhibited stronger signals for DNA regulatory factors (e.g. H3K4me3, transcription factor-binding sites) in exons, promoters, 5'UTRs and 5'genes but were not significantly different from con

SUBMITTER: Fan C 

PROVIDER: S-EPMC10290229 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature