Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report).

During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.

Sequence of a novel HLA-A2 allele in a haematopoietic stem cell donor of the international registry.

We report here the sequence of a new human leucocyte antigen-A2 allele, A*9251, identified in a volunteer haematopoietic stem cell donor of the international registry. A*9251 differs from A*02010101 by two nucleotides at codons 113-114, resulting in a single His>Asp substitution at codon 114.

Sequence of a new HLA-DR allele, DRB5*0106.

We report here the exon 2 sequence of a new HLA-DRB5 allele, DRB5*0106, that was identified in two volunteer bone marrow donors from the Swiss national registry. This new allele differs from DRB5*0101 by five amino acids at positions 67, 70, 71, 85 and 86. It is associated with DRB1*1501 and DQB1*0602. This unusual DRB1*1501-DRB5*0106 association increases the complexity of the DR2 group, although it appears to be very rare, at least in our population. HLA-DRB5*0106 can be readily detected upon DR generic oligotyping, provided the two probes that mark the major DRB5 subtypes, DRB5*0101 and DRB5*02, respectively, are included in the assay.

Sequence of HLA-DRB1*0818 in a bone marrow donor.

Exon 2 of a new HLA-DR8 subtype, DRB1*0818, was cloned and sequenced in a volunteer bone marrow donor. This new allele differs from DRB1*0805 by one single nucleotide in codon 67 resulting in an amino acid substitution from phenylalanine to isoleucine. Codon 67 dimorphism appears to be more frequent in DR8 and DR11 haplotypes. The HLA typing of the donor was A*0201/33 B*51/4403 Cw*0202/14 DRB1*0408/0818 DQB1*0302/0402. This new HLA-DR8 variant is very rare, at least in Caucasoids.