The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity.

ABSTRACT: Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory mutations are notoriously difficult to recognize. Most fundamentally, we are not yet adept at recognizing the sequence stretches in the human genome that are most important in regulating the expression of genes. For this reason, it is difficult to apply to the regulatory regions the same kinds of analytical paradigms that are being successfully applied to identify mutations among protein-coding regions that influence risk. To determine whether dosage sensitive genes have distinct patterns among their noncoding sequence, we present two primary approaches that focus solely on a gene's proximal noncoding regulatory sequence. The first approach is a regulatory sequen

SUBMITTER: Petrovski S 

PROVIDER: S-EPMC4557908 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature