Global analysis of 45 common polymorphic inverions in the human genome. Homo sapiens

Inversions are one type of structural variants linked to phenotypic differences and adaptation in multiple organisms. However, there is still very little information about polymorphic inversions in the human genome due to the difficulty of their detection. In this study we developed a new high-throughput genotyping method based on probe hybridization and inverse PCR, and we performed a complete study of 45 common human inversions of 0.1-415 kb in 551 individuals of seven diverse populations. We found that most inversions promoted by homologous recombination occur recurrently both in humans and great apes and they are not tagged by SNPs. Furthermore, there is an enrichment of inversions showing signatures of positive or balancing selection, diverse functional effects, such as gene disruption and gene-expression changes, or association with phenotypic traits. Therefore, our results indicate that the genome is more dynamic than previously thought and that human inversions have important functional and evolutionary consequences, making possible to determine for the first time their contribution to complex traits.