A human supergene: BRCA1, CCDC200, and U2 snRNAs

Abstract

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.