"THE VIRTUAL SEQUENCE": HLA TYPING INDEPENDENT FROM TECHNOLOGY AND INCREASING NUMBERS OF ALLELES.
          Erik H.Rozemuller, Marcel G.J.Tilanus. Department of Pathology, University Hospital Utrecht, Utrecht, the Netherlands.
          HLA typing results ultimately will become outdated. Typing results may be unambiguously identified based on technology and on the numbers of alleles recognized at the time of typing. Nevertheless they may become ambiguous with the recognition of new alleles. In addition, changes in current or new technology result in more and more dispersed information, which hampers comparison and merging of data. Moreover, matching procedures are tested based on epitope, or amino-acid (mis)matching. Ideally, high-resolution HLA typing is required. However, data in registries are not always suitable for these approaches. We propose the Virtual Sequence (VISE) as a description of all HLA data determined by a variety of techniques. Serological data can be compiled based on the specificity of antisera, or epitopes recognized. Information obtained by any PCR bases techniques (i.e. SSOP, SSP, SBT, or combinations) is compiled in one format; the VISE describes which nucleotides have been proven to be present, or absent. In addition, the proven cis or trans configuration of nucleotides is described. Family data can be included to describe the linkage between alleles of different loci. The VISE is the basis for all further analyses. The level of typing resolution can be defined based on the combined data represented in VISE. Ambiguities can be resolved; allele assignment is performed with the most updated allele libraries, using all sequence information gathered in past by any technique. Newly recognized ambiguities are resolved by adding new information. To study haplotypes, typing results, combined with intron and promoter data, and polymorphism of other genes in the MHC region are compiled. Matching procedures can be tested and used, which are not only based on serological group equivalents, but also on other criteria, such as shared, or excluded motifs/amino-acids, and expression.