LOCALIZATION OF NEW GENES AND MARKERS TO THE DISTAL PART OF THE HUMANMAJOR HISTOCOMPATIBILITY COMPLEX (MHC) REGION AND COMPARISON WITH THEMOUSE - NEW INSIGHTS INTO THE EVOLUTION OF MAMMALIAN GENOMES

We have refined and extended the map of the distal half of the human m ajor histocompatibility complex. The map is continuous from HLA-E to 1 000 kb telomeric of HLA-F and includes six new markers and genes. In a ddition, the corresponding sequences that were not previously mapped i n the mouse genome have been located. The human and the mouse organiza tions have therefore been compared. This comparison allows us to demon strate that the structure of the distal part of the MHC is similar in the two species. In addition, this comparison shows the presence of a breakpoint of synteny telomeric of the distal part of the H-2 region. Indeed, the region telomeric of HLA in human is found on a chromosome different from that carrying H-2 in mouse. The mapping analysis of par alogous genes (structurally related genes) around the breakpoint shows that the human organization probably represents the putative human/mo use ancestral one. This evolutionary breakpoint was precisely mapped i n human, and the surrounding region was cloned into yeast artificial c hromosomes. Finally, we show that the region found around the breakpoi nt was involved several times in chromosome recombinations in the mous e lineage, as it seems to correspond also to the t-complex distal inve rsion point. (C) 1995 Academic Press, Inc.