Dosage sensitivity is a major determinant of human copy number variant pathogenicity.

ABSTRACT: Human copy number variants (CNVs) account for genome variation an order of magnitude larger than single-nucleotide polymorphisms. Although much of this variation has no phenotypic consequences, some variants have been associated with disease, in particular neurodevelopmental disorders. Pathogenic CNVs are typically very large and contain multiple genes, and understanding the cause of the pathogenicity remains a major challenge. Here we show that pathogenic CNVs are significantly enriched for genes involved in development and genes that have greater evolutionary copy number conservation across mammals, indicative of functional constraints. Conversely, genes found in benign CNV regions have more variable copy number. These evolutionary constraints are characteristic of genes in pathogenic CN

SUBMITTER: Rice AM 

PROVIDER: S-EPMC5309798 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature