ALLELIC AND INTERLOCUS COMPARISON OF THE PERB11 MULTIGENE FAMILY IN THE MHC

The major histocompatibility complex (MHC) contains at least a hundred genes over 4 megabases of DNA. Within the MHC there are several new m ultigene families which have been recently described. PERB11 is a mult igene family which occurs over the class I and central region of the M HC. Two members of the family have been shown to be functional and sha re domains with members of the supergene family including HLA class I, FcRn, and Zn-alpha 2-glycoprotein molecules. The two functional membe rs are contained within an area of the MHC which has been associated w ith increased susceptibility to autoimmune diseases such as insulin-de pendent diabetes mellitus and also rapid progression to AIDS following HIV-1 infection. Intralocus and interlocus differences between PERB11 .1 and PERB11.2 include: (1) several nucleotide substitutions leading to amino acid changes; (2) presence and absence of potential glycosyla tion sites; (3) insertions and deletions leading to a frame shift resu lting in diversity at the amino acid level and an early termination si gnal. There are ten different alleles of PERB11.1 including one allele which contains a frame shift in the transmembrane region causing a pu tative truncated molecule lacking the cytoplasmic tail. The significan ce of this polymorphism in disease associations is under investigation . The most divergent domain is the transmembrane region when PERB11.1 and PERB11.2 are compared. The results suggest that these two molecule s may have different functions.