Fig. 9

Schematic summary of present findings. Public genetic-variant databases are employed to identify density-based hotspots and clusters, which are found to be dynamic centres with accentuated positive and/or negative changes in the genome. On the one hand, they work in conjunction with positive selection to enhance sequence diversity, evolution of specific genes and pathways, and development of functional genomic features. On the other hand, they are co-localized with destabilizing retrotransposon elements, and occurrences of homologous recombination (HR) in the early DNA replication phases, and non-homologous (NH) repair in the late DNA replication phases. Their associations with high GWAS discovery rates and somatic variants signal the importance of associations with complex traits and diseases, and therefore their utility as the basis for a potential “Common Disease-Hotspot Variant” strategy in a search for the missing heritability in association studies