HETEROGENEITY IN RATES OF RECOMBINATION IN THE 6-MB REGION TELOMERIC TO THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX

Analysis of 784 informative meioses in the CEPH pedigrees revealed a t otal of 22 recombination events having occurred in the 6-Mb region bet ween D6S265 (70 kb centromeric of HLA-A) and D6S276. These 22 breakpoi nts were localized with respect to anonymous polymorphic markers, lead ing to a detailed genetic map of the region telomeric to the human maj or histocompatibility complex. A nonrandom pattern of recombination wa s observed throughout this region: the low recombination rate of 0.19% within the 4-Mb interval centromeric to the HLA class I-like candidat e gene for hemochromatosis indeed contrasts with the approximate 1% ra te observed within the most telomeric two megabases. This reduced rate of recombination may be due to selective constraints depending on env ironmental factors related to immunity and iron status or to structura l variations hampering proper meiotic pairing of homologous sequences. Population data from other human genome segments are now needed to de termine whether linkage disequilibrium extending over 4 Mb is unique t o this region. (C) 1997 Academic Press.