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TITLE: THE STRUCTURE OF INTRON 1 DEMONSTRATES STRONG LINEAGE SPECIFICITY IN HLA–DQB1 ALLELES

Holger–Andreas Elsner,¹ Sabine Kriens,¹ Rainer Blasczyk.<sup>1

1</sup>Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany

For many HLA–DQB1 alleles coding sequences still need to be completed, and almost no sequence data about non–coding regions exist. In this study we have sequenced intron 1 of 30 haplotypes from samples of various ethnic groups, representing 16 alleles. Phylogenetic relationships, and synonymous and nonsynonymous nucleotide substitution rates &pgr; were computed of intron 1 and the adjacent exons 1 and 2, respectively. The dendrograms showed clear lineage specificity in all three parts of the gene. This finding may be explained by the low CpG content in intron 1 (2.8%) and exon 1 (3.7%) which may reduce the probability of long interlineage recombination events in these parts of the gene. In the segments of exon 2 encoding the presumed antigen recognition site, the non–synonymous nucleotide substitution rate &pgr;_a exceeds the synonymous nucleotide substitution rate &pgr;_s, which thus demonstrates overdominant or balancing selection. The data obtained in our study for the first time provide additional evidence in support of this conjecture since &pgr;_s of exon 1 (0.07787) and exon 2 (0.08688) exceed &pgr; of intron 1 (0.06033), thus indicating intronic homogenization due to interallelic recombination and subsequent genetic drift. %Apart from further phylogenetic studies about HLA–DQB1 diversity, the sequence data obtained in our study may prove valuable for the development of a haplotype–specific sequencing strategy for exon 2, and for the explanation of recombination events in newly described HLA–DQB1 alleles.