Mutational and selective effects on copy-number variants in the human genome.

Comprehensive descriptions of large insertion/deletion or segmental duplication polymorphisms (SDs) in the human genome have recently been generated. These annotations, known collectively as structural or copy-number variants (CNVs), include thousands of discrete genomic regions and span hundreds of millions of nucleotides. Here we review the genomic distribution of CNVs, which is strongly correlated with gene, repeat and segmental duplication content. We explore the evolutionary mechanisms giving rise to this nonrandom distribution, considering the available data on both human polymorphisms and the fixed changes that differentiate humans from other species. It is likely that mutational biases, selective effects and interactions between these forces all contribute substantially to the spectrum of human copy-number variation. Although defining these variants with nucleotide-level precision remains a largely unmet but critical challenge, our understanding of their potential medical impact and evolutionary importance is rapidly emerging.