Abstract

Copy number variants (CNVs) have recently emerged as an important cause of human disorders. Most pathogenic CNVs are large and contain many genes, and identification of the specific disease-causing genes has proven to be challenging. Using an evolutionary genetic approach, we tried to identify such genes through the mapping of ohnologs, genes retained after ancestral whole-genome duplication events. Comparing the proportion of ohnologs between potentially pathogenic and nonpathogenic sets of CNVs, we found that ohnologs are significantly overrepresented in the pathogenic sets. Our results support the hypothesis that ohnologs are ancestral dosage-sensitive elements that may be responsible for some of the deleterious phenotypes observed for CNVs.