Dosage Sensitive Genes in Evolution and Disease

Most genes in the genome tolerate dose changes through expression noise, gene duplication and copy number variation. However, a subset of the genome is dosage sensitive and is associated with the observed pathogenicity of some CNVs. These dosage sensitive genes are interesting genes that operate in a concentration dependent or dosage-balanced way, and are frequently associated with development. We have found that dosage sensitivity influences the evolution of genes in characteristic and predictable ways and that these characteristics can be used to identify candidate dosage sensitive genes in the genome. In particular, we found that genes retained after whole genome duplication are frequently dosage sensitive and that the presence of such genes in the genome creates CNV deserts where CNVs are depleted, probably due to deleterious effects of the dosage alterations