A RADIATION HYBRID MAP OF BTA23 - IDENTIFICATION OF A CHROMOSOMAL REARRANGEMENT LEADING TO SEPARATION OF THE CATTLE MHC CLASS-II SUBREGIONS

Bovine chromosome 23 (BTA23) contains the bovine major histocompatibil ity complex (MHC) and is thus of particular interest because of the ro le of MHC genes in immunity. Previous studies have shown cattle MHC cl ass II genes to be subdivided into two distinct subregions separated b y a variable genetic distance of 15-30 cm, To elucidate the genetic ev ents that resulted in the present organization of the class II and oth er MHC genes, a framework radiation hybrid (RH) map of BTA23 was devel oped by testing DNA samples from a 5000 rad whole genome RH panel. Twe nty-six markers were screened with an average retention frequency of 0 .27, ranging from 0.14 to 0.42, Total length of the chromosome was 220 cR(5000), with 4.1 cR(5000)/cM when compared to linkage data. Gene or ders for the markers common to both the RW framework map and the conse nsus framework linkage map are identical. Large centiray intervals, D2 3523-D23S7, DYA-D23S24 and CYP21-D23S31, were observed compared to lin kage distances. These data may indicate a much larger physical distanc e or suppression of recombination in the interval separating the class II subregions and also within the class I region than previously esti mated. Comparison of 13 Type I genes conserved between BTA23 and the h uman homolog HSA6p suggests the occurrence of an inversion encompassin g the centromeric half of the bovine chromosome, thus explaining the l arge distance between the bovine class IIa and IIb clusters. These res ults exemplify the power of RH mapping in solving problems in comparat ive genomics and evolution. Furthermore, noncongruence of the genetic and physical RH map distances indicates that caution must be observed in using either resource alone in searching for candidate genes contro lling traits of economic importance. (C) 1998 Academic Press.