GENOMIC CHARACTERIZATION OF THE REGION BETWEEN HLA-B AND TNF - IMPLICATIONS FOR THE EVOLUTION OF MULTICOPY GENE FAMILIES

The major histocompatibility complex (MHC) contains genes which confer susceptibility to numerous diseases and must be important in primate evolution. In some instances, genes have been mapped to the region bet ween human histocompatibility leukocyte antigen (HLA)-B and tumor necr osis factor (TNF) but precise localization has proven difficult especi ally since this region is subject to insertions, deletions, and duplic ations. Utilizing computer similarity searches and coding prediction p rograms, we have identified several potential coding sequences between HLA-B and TNF. Three of these sequences, PERB11.2, PERB15, and PERB18 , are similar to members of multicopy gene families that are located i n other regions of the MHC. The identification of numerous fragmented and intact retroelements (L1, Alu, LTR, and THE sequences) flanking th e PERB11 and PERB15 genes suggests that these retroelements are involv ed in the duplication process, The evaluation of candidate genes for d isease susceptibility within the MHC is complicated by their similarit y to other members of multicopy gene families, The determination of se quence differences within and between species provides a strategy with which to investigate the candidate genes between HLA-B and TNF.