The Complex Mutation Pattern of a Microsatellite

DQCAR is a (CA) n microsatellite located in the HLA class II region and tightly linked to HLA–DQB1 . Previous studies showed a strikingly low level of size variation in DQCAR alleles within an extensive subfamily of HLA–DQ subtypes ( DQ1 ). DQCAR alleles in non- DQ1 subtypes showed a higher degree of size polymorphism. In this study sequence analysis demonstrates that DQ1 - associated DQCAR alleles have a single C → A nucleotide substitution interupting the CA repeat array. Frequent CA → GA mutations are also observed in DQ1 -associated microsatellites with identical allele sizes. In contrast, DQCAR alleles associated with non- DQ1 haplotypes display a perfect CA repeat sequence and the variation in allele size is attributable only to differences in the number of CA repeats. Our results imply that several mutational mechanisms are involved in the generation of allelic diversity within the same microsatellite locus. The possibility of different mutation rates in the same locus should to be taken into account when using these markers in evolutionary and disease studies. [The sequence data described in this paper have been submitted to the GenBank data library under accession nos. U96944 – U96962 and S87165 .]