EVOLUTIONARY RELATION BETWEEN HLA-B INTRON SEQUENCES AND MITOCHONDRIAL DNA IN THE AUSTRALIAN ABORIGINAL POPULATION.
S. A. Scheltinga, C. F. Vogelaar, E. H. Rozemuller and M. G. J. Tilanus (Dept. of Pathology, University Hospital Utrecht, Utrecht, the Netherlands).


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Recent studies have shown that HLA-B alleles arise from a common ancestor, because the intron sequences are highly conserved. HLA-B is the most polymorphic gene of the MHC class I loci and it is shown that not only the exons, but also the introns may be involved in the generation of HLA-B alleles. MtDNA (mitochondrial DNA) is a useful marker in evolutionary studies. MtDNA has a 5-10 times higher mutation rate than the nuclear genes, is maternally inherited and no recombination takes place. Our interest is to correlate mtDNA mutations with HLA-B intron polymorphism. This gives us the opportunity to identify clusters of HLA-B alleles based upon their evolutionary relationships. This will give a higher chance for finding a donor for transplantation, especially in populations which have restricted rare HLA haplotypes. HLA-B typing is performed by SBT (Sequencing Based Typing) from 39 Aboriginal Australians of the Yuendumu tribe from the Central Desert. Of this samples also a 380 bp region of the D (displacement)-loop of mtDNA is obtained by SBT. Of both HLA-B intron sequences and the mtDNA phylogenetic trees are designed and results in clusters. The 39 samples represented 7 different HLA-B alleles and 16 different mtDNA sequences. Within the first hypervariable segment of mtDNA the D-loop, most individuals showed homoplasmy (one kind of mtDNA with a homopolymeric tract of cytosines interrupted by one thymidine at pos. 16189). 11 Individuals showed length heteroplasmy (The T -> C transition at this position results in a variant which produces a characteristic blurred sequence in nucleotides beyond the C-tract). The mutations in length heteroplasmy were resolved by using an internal sequence primer. One sample showed heteroplasmy of a polymorphism.