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Sequencing studies were performed in three previously described microsatellite and minisatellite markers located within the HLA-DQ region, DQCAR, DQCARII and G51152. Multiple nucleotide substitutions that did not change size polymorphisms were observed in all three markers. In all loci, the number of core repeats did not correlate with neighboring DQ allele sequence motifs while single nucleotide changes within or flanking the microsatellite sequence did. This result indicates higher mutation rates for microsatellite expansions/contractions than for nucleotide substitutions in these loci. Further analysis indicated an almost complete phylogenetic correspondence between DQCAR single nucleotide polymorphisms (SNPs) and DQB1 sequences on one side (1.0-1.5 kb apart) and a complete relationship between DQCARII and DQA1 sequences on the other (4.5 kb apart). In contrast, G51152 sequences did not correspond perfectly with DQB1 allelic sequences, thus suggesting the existence of several ancestral crossovers between this marker and DQB1 (20-25 kb). Sequencing microsatellites might be useful in disease mapping studies by increasing marker informativeness and by helping in the interpretation of association study results. It is also proposed that SNPs within the flanking region of CA repeats could be used to develop biallelic markers from already available mapped microsatellite markers.
View details for Web of Science ID 000074956100002
View details for PubMedID 9714469