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.

HLA-D typing with homozygous cells identified in an American indigenous isolate. II. Family studies and D/DR relationship.

Twelve American Indian nuclear families with 2-5 siblings have been HLA-D typed using mixed lymphocyte cultures and clusters of homozygous typing cells (HTC) of Caucasoid origin to detect DW1-DW7 and typing cells of American Indian origin to detect LD5A, LD15A and LD15B antigens. Results obtained demonstrate complete absence of DW1-DW7 in these families and illustrate the inheritance and segregation of LD5A, LD15A and LD15B. DR typing results obtained with the 8th International Histocompatibility Workshop genetic set of antisera indicate inheritance in coupling of DR2 with LD5A, of DR6.2 (DR3+6, MT1 negative, MT2 positive) with LD15A, and of DRW8 with LD15B. The existence of MLC activating antigen(s) different to DW4, yet associated to DRW4 in this population is postulated. The D/DR relationship present in this American Indian isolate demonstrate once more that DR2 can be inherited in combination with an HLA-D antigen different to DW2, and that LD15A HTC define a second sub-cluster of the broad DW6 specificity group, which is inherited with DRW6.2 and BW62 antigens in the Warao population.

HLA--D typing with homozygous cells identified in an American indigenous isolate. I. Population studies.

Lymphocytes from six individuals homozygous for their HLA--A, --B, --C and --D loci belonging to an American indigenous group, the Warao, have been used as typing cells to detect HLA--D determinants in 121 donors from the same indigenous isolate and in 71 donors of mixed ethnic origin living in Venezuela. Two determinants responsible for strong proliferation in mixed lymphocyte cultures have thus been identified. Four HLA--A2, B5 cells (r values between 0l72 and 0.57) identify a determinant provisionally called LD5a showing a gene frequency of 0.30 among the Warao and of 0.09 among the population of mixed ethnic origin. The nearest B locus antigen to this new specificity among the Warao is HLA--B5 (r value = 0.20). A second determinant identified by two HLA--A2, B15 sisters (r values of 0.71) shows a gene frequency of 0.15 among the Warao and of 0.03 among the mixed population. The latter is related to Dw8 as shown by results of the VI and VII Histocompatibility Workshops, and is weakly associated (r value of 0.28) to HLA--B15 among the American indigenous population tested.

LD homozygous cells in the Warao population: a possible new allele at the LD1 locus within the main histocompatibility region in man.

A Venezuelan isolate indigenous population, the Warao, with a very large proportion of HL-A identical unrelated subjects non-reacting in MLC, has been considered a good potential source of LD homozygous cells. Cultures with lymphocytes from the members of several selected Warao families were performed with this aim and results obtained from three families are reported. In two of the families the parents share haplotype 2,5 and two of the siblings are SD double homozygous 2,5; in the third family, the common haplotype was 2,W15 and two of the siblings are also double homozygous 2,W15. Mixed lymphocyte cultures within the families have revealed that the SD homozygous children do not stimulate the cells from either parent thus being LD homozygous as well. Negative bilateral stimulation between 2,5 LD homozygous cells indicates that the LD1 allele carried by these individual's lymphocytes is the same; the negative MLC response of the 2,W15 LD homozygous cells to the 2,5 cells used as stimulators suggest either that their LD determinant is identical or the LD W15 allele is included in the LD5. As the Warao show a very large proportion of MLC identical individuals and a very high incidence of HL-A5 and W15, it is postulated that the LD allele(s) here described will be found in high frequency in this population.