Unique HLA-DR/DQ associations revealed by family studies in Warao Amerindians. Haplotype and homozygosity frequencies

HLA-A, Cw, B and A, Cw, B, DR genotypes have been assigned, respectively, to 318 and 175 Warao Amerindians belonging to 73 sibships, who were tested with International Histocompatibility Workshop reagents. Only 33% of the theoretically possible three-loci and 7% of the possible four-loci haplotypes were found, with 10 and 6 of them accounting, respectively, for 75% of the total observed. This limited haplotype variability, expected in an inbred population, was not accompanied by either an increased or a decreased frequency of homozygous individuals, as demonstrated by population and family analysis. Inheritance of five HLA loci haplotypes in 20 families showed the expected distribution of parental haplotypes in sibling pairs. The study revealed DR2sh (DRw16), DR4 and DRw6 in association with DQw7, and DRw8 with DQw4, and significant positive linkage disequilibria between Bw62 CW1, B51 DRw16, B39 DR4, Bw62 DRw6, and DRw8 DQw4. The DR2-DQw7 and DRw6-DQw7 associations and the first three paired loci disequilibria mentioned are described for the first time in Amerindians and have not yet been found among Japanese, Negroid, or Caucasoid populations.