Diversity of Human Copy Number Variation and Multicopy Genes

Copy number variants (CNVs) affect both disease and phenotypic variation but it has been difficult to accurately genotype human copy number variation lying within heavily duplicated, highly identical sequence. By analyzing short-read mapping depth for 159 human genomes we demonstrate accurate estimation of absolute copy number for duplications as small as 1.9 kbp, ranging from 0-48 copies. From this we identified 4.1 million "singly unique nucleotide" (SUN) positions informative in distinguishing specific copies, and use them to resolve copy number variation of specific paralogs within highly duplicated gene families. These data also defined human-specific expansions in genes associated with brain development, and detected signatures consistent with gene conversion in the human species demonstrating the ability to assay both copy and content of complex regions of the human genome.