The phylogenies of introns 4-7 demonstrate an inconsistent pattern between human leukocyte antigen-C group topologies.

In this study, we have sequenced introns 4-7 in 31 human leukocyte antigen-C (HLA-C) alleles representing all allelic groups. Intron sequences show a patchwork pattern of polymorphism. Bootstrap support for phylogenetic lineages and for differentiation between groups is limited due to the high homology of intron sequences, where the substitution of a single nucleotide may lead to the assignment to different clusters. The intron data suggest the idea of a Cw*06/Cw*12 family, which is closely related to a hypothetical Cw*05/Cw*08 family. Moreover, a third family consisting of Cw*01/Cw*04/Cw*18 may exist. The intron data compiled in our study may be the basis for further sequencing studies. The detection of three novel alleles (Cw*0401new, Cw*140201new, and Cw*1701new) suggests that the HLA-C polymorphism might have been strongly underestimated to date.