A human supergene: BRCA1, CCDC200 , and U2 snRNAs

BRCA1 occurs on one of two major haplotypes in populations of European and Asian ancestry that show signs of selection and functional differences. Near-maximal linkage disequilibrium associated with these haplotypes extends for more than 300 kilobases from RND2 to RNU2 . There is greater haplotypic diversity in populations from Africa, with the majority haplotype in Europe and Asia a minority haplotype in Africa. Recombination across this region is very rare or absent, both within Africa and outside of Africa, with haplotypes inherited as ‘alleles’ of a supergene. The polymorphism appears to be maintained by some form of balancing selection. We analyzed the repeat structure of the RND2–RNU2 supergene using the CHM13 telomere-to-telomere genome assembly. The most notable feature is the highly regular array of 6.1-kb RNU2 repeats. Immediately adjacent to the RNU2 array are retroviral sequences that may play a role in the concerted evolution of the repeats. Other structure-forming sequences from the RND2– RNU2 region are predicted to be sources of replicative stress and may interfere with meiotic chromosome synapsis.