RESEARCH ARTICLE Intronic CNVs and gene expression variation in human populations 1 2 1,3☯ 4☯ Maria RigauID , David JuanID , Alfonso Valencia *, Daniel RicoID * 1 Barcelona Supercomputing Center (BSC), Barcelona, Spain, 2 Institut de Biologia Evolutiva, Consejo Superior de Investigaciones CientõÂficas±Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, Barcelona, Spain, 3 Institucio Catalana de Recerca i Estudis AvancËats (ICREA), Barcelona, Spain, 4 Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom ☯ These authors contributed equally to this work. *
[email protected] (AV);
[email protected] (DR) a1111111111 a1111111111 a1111111111 a1111111111 Abstract a1111111111 Introns can be extraordinarily large and they account for the majority of the DNA sequence in human genes. However, little is known about their population patterns of structural varia- tion and their functional implication. By combining the most extensive maps of CNVs in human populations, we have found that intronic losses are the most frequent copy number OPEN ACCESS variants (CNVs) in protein-coding genes in human, with 12,986 intronic deletions, affecting Citation: Rigau M, Juan D, Valencia A, Rico D 4,147 genes (including 1,154 essential genes and 1,638 disease-related genes). This intro- (2019) Intronic CNVs and gene expression nic length variation results in dozens of genes showing extreme population variability in size, variation in human populations. PLoS Genet 15(1): with 40 genes with 10 or more different sizes and up to 150 allelic sizes. Intronic losses are e1007902. https://doi.org/10.1371/journal. pgen.1007902 frequent in evolutionarily ancient genes that are highly conserved at the protein sequence level.