Saturation mutagenesis of twenty disease-associated regulatory elements at single base-pair resolution.

ABSTRACT: The majority of common variants associated with common diseases, as well as an unknown proportion of causal mutations for rare diseases, fall in noncoding regions of the genome. Although catalogs of noncoding regulatory elements are steadily improving, we have a limited understanding of the functional effects of mutations within them. Here, we perform saturation mutagenesis in conjunction with massively parallel reporter assays on 20 disease-associated gene promoters and enhancers, generating functional measurements for over 30,000 single nucleotide substitutions and deletions. We find that the density of putative transcription factor binding sites varies widely between regulatory elements, as does the extent to which evolutionary conservation or integrative scores predict functional effec

SUBMITTER: Kircher M 

PROVIDER: S-EPMC6687891 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature