A PRECISE MEIOTIC MAP IN THE CLASS-I REGION OF THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX

Human families in which recombinant meiotic event(s) are known to have occurred are powerful tools with which to analyze more precisely the structures of defined genomic regions, especially unstable areas. Such families allow the determination of the haplotypes of each member and , taking into account the recombinant event, it is possible to localiz e very precisely the point of crossover. Using families in which cross overs between the genes HLA-A and -B have occurred, we have constructe d a meiotic map localizing the meiotic breakpoint events with respect to both anonymous markers and the principal genes of the region. Such mapping, which depends on the direct analysis of genomic DNA, is essen tial for fine structural analysis and is a powerful means of verificat ion of the order and the localization of markers: physical mapping alo ne, using yeast artificial chromosomes, presents some uncertainties du e to the numerous chimeras and inversions that can be produced. The es tablishment of this map will allow us to determine efficiently the pre cise location for new markers already localized to the map region. Thr ee microsatellites (D6S265, D6S276, and D6S306), localized in the HLA region by linkage analysis, have been precisely located with respect t o the points of recombination in the class I region. The sites of meio tic recombination in the MHC class I region seem to be not randomly di stributed but in the majority of cases occurred between HLA-C and the microsatellite D6S265. This study also shows two cases of abnormal seg regation of alleles. We discuss how these mutations correspond to a sp ontaneous mutation event at the somatic or germinal level. (C) 1995 Ac ademic Press, Inc.