is found primarily in the African American population. Most of the 28 DRB1*03 alleles (22 out of 28, 79 percent) were not observed in the testing, suggesting that they will be found in less than 1 percent of the population.

The frequencies of HLA haplotypes found in individuals differ among ethnic/racial groups. Some haplotypes are common to several populations; others may be predominantly confined to one particular population group. Most of the theoretical haplotypes are rarely observed. The most common haplotype in whites (A1,B8,DR3) is the second most frequent haplotype in African Americans and the third most frequent haplotype in Latinos, but it is the 54th most frequent haplotype in Asian Americans (52). It is likely that not all potential haplotypes will be found. When large databases of HLA typed individuals are analyzed, only a small percent of potential HLA phenotypes are found. Using serologic assignments from the National Marrow Donor Program, of the predicted 19,536,660 HLA-A, -B, -DR phenotypes, only 1.6 percent were observed (52).

Information of the frequencies of specific alleles and haplotypes (defined at allele level) in specific populations is limited (72). Populations have been studied through the International Histocompatibility Workshops, but the typing methods and resolution of testing have been inadequate to detect the full extent of HLA diversity (38, 42). Lack of allele level data seriously impacts our ability to predict the probability of finding an allele matched donor for patients and our ability to determine the most effective size for a registry or bank (44, 45).

Understanding common haplotypes or allele associations is useful for predicting which alleles are most likely to be present in donors who have only low resolution typing information and no family data to define haplotypes. For this reason, information on the ethnic background of the volunteer donors is often provided in registries and umbilical cord blood banks.

TISSUE TYPING

Clinical Testing and Quality Control

Testing to identify HLA allelic differences among individuals is classified as a high complexity assay by Clinical Laboratory Improvement Amendments (CLIA) guidelines (http://www.fda.gov/cdrh/CLIA/categorization.html). The complexity arises from the need to detect multiple loci, the similarity among loci and alleles, the complex nature of the polymorphism (multiple polymorphic motifs shared among alleles define an allele), and the continuing discovery of new alleles. HLA testing is routinely carried out by laboratories using either commercial and/or “home-made” reagents.

The American Society for Histocompatibility and Immunogenetics (ASHI), the European Federation for Immunogenetics (EFI) and other orga-



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