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The number of alleles described for each of the indicated HLA loci is shown in the middle column. The number of expression variant alleles is indicated in adjacent columns. Data represent WHO listed alleles as of July 2004.52

The number of alleles described for each of the indicated HLA loci is shown in the middle column. The number of expression variant alleles is indicated in adjacent columns. Data represent WHO listed alleles as of July 2004.52

HLA-A, -B, -C, -DRB1) and tissue types. However, the practical numbers encountered are much smaller on two accounts. First, many of the described alleles occur at very low frequency in most or all populations. Thus, the majority of individuals in a population can be accounted for by a relatively limited number of alleles at the commonly typed loci.57 58 Second, alleles at different loci appear together more frequently than expected by chance due to linkage disequilibrium.6'59'60 As an example, HLA-A*0101,B*0801, Cw*0701,DRB1*0301,DQB1*0201 may represent ~5% of the haplotypes in Northern European populations despite an expectation of about 0.007% based on the product of the individual gene frequencies. Patients with common or linkage HLA haplotypes more often find well-matched donors in unrelated-donor registries than do those with uncommon associa-tions.61-63

The level of polymorphism of the HLA genes is not equally distributed among the coding exons. For class I HLA genes, exons 2 and 3 are more polymorphic than other exons. For class II genes, exon 2 is the most polymorphic exon. As noted earlier, these exons encode the protein domains that form the peptide binding structure and interface for the T-cell222627 and NK-cell receptors.43,44,64 Most of the highly polymorphic positions of these domains are involved in peptide-binding or TCR contact26 (Figure 93.5). It may be that matching for these residues is more important than others in reducing adverse transplant outcome, although data supporting this are lacking as of yet.

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