Recombination within the human MHC

Recombination (crossing over) in the human MHC is thought to have played a role in generation of novel alleles at various HLA loci. It is also responsible for the diversity observed at the haplotype level, although the functional consequences of this activity are not clear. Historic and family studies of recombination have provided estimations of recombination fractions across the MHC and identified potential hotspots for recombination in the class II region. Other characteristics of recombination in the human MHC such as haplotype specificity in recombination frequency and localized sequence motifs involved in recombination have been considered, but have been difficult to address given the constraints of human population studies. Single-sperm typing holds promise in overcoming some of the limitations inherent in the study of recombination in human populations. Both family-based and sperm typing analyses of recombination, along with our knowledge of linkage disequilibrium patterns in the MHC, may provide novel information regarding the evolution of HLA haplotypes that will be difficult to obtain by other means.