Assessing the digenic model in rare disorders using population sequencing data.

ABSTRACT: An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in diff

SUBMITTER: Moreno-Ruiz N 

PROVIDER: S-EPMC9712436 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature