COMPLEX GENE CONVERSION EVENTS IN GERMLINE MUTATION AT HUMAN MINISATELLITES

Mutation at the human minisatellites MS32, MS205 and MS31A has been in vestigated by characterizing mutant alleles in pedigrees and in the ca se of MS32 by direct analysis of mutant molecules in single sperm. Mos t mutations at all three loci are polar, involving the preferential ga in of a few repeat units at one end of the tandem repeat array. Incomi ng repeats can be derived from the same allele or the homologous chrom osome, though they are frequently rearranged during mutation. Lack of exchange of flanking markers suggests the involvement of complex conve rsion-like events in the generation of mutant alleles. At MS32, high f requency mutation processes in sperm appear to be largely germline spe cific and to occur at a constant rate irrespective of allele size. Tog ether with mutational polarity, this implies that germline instability is controlled by elements outside the tandem repeat array.