Characterization of the HLA-C*07:01:01G allele group in European and African-American cohorts.

The HLA-C07:01:01G allele group consists of three nonsynonymous alleles, C07:01:01, C07:06 and C07:18, plus C07:01:02, which is synonymous to C07:01:01. All of these alleles have identical exons 2, 3 and 4, but differ in exons 5 or 6. Therefore routine sequence-based typing (SBT) of exons 2 and 3 is unable to resolve these subtypes, resulting in ambiguous typing results in population and disease cohort studies. In the present study, we fully characterized C07:01:01G subtypes in European and African Americans and examined their relative frequency distributions. In European Americans C07:01:01G is predominantly represented by C07:01:01 (94.4%), whereas C07:01:02 (1.1%) and C07:18 (4.5%) were detected relatively infrequently. In African Americans C07:18 (42.4%) showed a high frequency similar to that of C07:01:01 (44.7%) whereas C07:06 was detected at a low frequency (4.7%). C07:06 was found exclusively on B44:03 carrying haplotypes in both ethnic groups, but C07:18 showed multiple linkage relationships with HLA-B. These results demonstrate that C07:01:01G as defined by routine SBT is a heterogeneous group of alleles, especially among individuals of African origin. If C*07:01:01G subtypes prove to bear divergent functional significance, it would be necessary to include these subtypes in routine HLA-C typing for clinical transplantation and disease association studies.