Extensive nucleotide variability within a 370 kb sequence from the centralregion of the major histocompatibility complex

The recent availability of the genomic sequence spanning the central and te lomeric end of the major histocompatibility complex (MHC) has allowed a det ailed study of its organisation, gene content and level of nucleotide varia bility. Previous analyses of nucleotide variability in the MHC have focused on the coding regions of the human leukocyte antigen (HLA) Class I and II genes. Non-coding nucleotide variability has been considered a by-product o f exonic diversity. However, with the advent of genomic sequencing, the ext ent of non-coding nucleotide variability within the MHC has just begun to b e appreciated. In this study, we compared different human haplotypes in 370 kb of sequence in the central region of the MHC to show the following: 1. unusually high levels of non-coding nucleotide variability, up to 80 tim es greater than elsewhere in the genome; 2. non-coding nucleotide variability greater than 1% at nucleotide sites di stant to the Class I genes; 3. nucleotide variability greater than 1% maintained over regions containin g highly linked loci; and 4. distinct troughs and peaks in the level of nucleotide variability. We will discuss these observations in relation to a possible role of nucleo tide variability in the organisation of the MHC. (C) 1999 Elsevier Science B.V. All rights reserved.