title: Resolution of HLA-B*44:02:01G, -DRB1*14:01:01G and -DQB1*03:01:01G reveals a high allelic variability among 12 European populations.
abstract: Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B*44:02:01G, DRB1*14:01:01G and DQB1*03:01:01G, was undertaken in 12 European populations. Ambiguities were resolved by polymerase chain reaction-sequence-specific amplification (PCR-SSP) or PCR-sequence-based typing (PCR-SBT) in a total of 5095 individuals. The results of the DRB1*14:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB1*14:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the B*44:02/44:27 ambiguity showed that B*44:27 had a high relative ratio in Slovenians (25.5%) and Bulgarians (37%) and low in French and Swiss (0.02-1%), and was not observed in Greeks and Italians. The highest relative ratio of DQB1*03:19 was found in Portuguese (11%), by contrast with low ratios (0-3%) in the other five populations. Analysis of the A, B, DRB1 phenotypes and family-derived haplotypes in 1719 and 403 individuals positive for either HLA-B*44:02G or DRB1*14:01G ambiguities, respectively, showed some preferential associations, such as A*26∼DRB1*14:01, B*35∼DRB1*14:01, B*38∼DRB1*14:01 and B*44:27∼DRB1*16. Because these ambiguities are located outside the peptide-binding site, they may not be recognized by alloreactive T-cells. However, because of strong linkage disequilibrium (LD), the DRB1*14:01 vs DRB1*14:54 and the B*44:02 vs B*44:27 mismatches are associated to DRB3-, and C-mismatches, respectively. These results are informative for algorithms searching unrelated hematopoietic stem cell donors. For B*44:27-positive patients, searches are expected to be more successful when requesting donors from Southeastern-European ancestry. Furthermore, the introduction of human leukocyte antigen (HLA)-typing strategies that allow resolving exon 4 (for class I) and exon 3 (for class II) polymorphisms can be expected to contribute significantly to population genetics studies.
authors.affiliation: Tissue Typing Center, Blood Transfusion Center of Slovenia, Ljubljana, Slovenia.
authors.forename: B
authors.initials: B
authors.lastname: Vidan-Jeras
authors.forename: S
authors.initials: S
authors.lastname: Buhler
authors.forename: V
authors.initials: V
authors.lastname: Dubois
authors.forename: Z
authors.initials: Z
authors.lastname: Grubic
authors.forename: M
authors.initials: M
authors.lastname: Ivanova
authors.forename: T
authors.initials: T
authors.lastname: Jaatinen
authors.forename: D
authors.initials: D
authors.lastname: Ligeiro
authors.forename: M-L
authors.initials: ML
authors.lastname: Lokki
authors.forename: C
authors.initials: C
authors.lastname: Papasteriades
authors.forename: F
authors.initials: F
authors.lastname: Poli
authors.forename: M
authors.initials: M
authors.lastname: Spyropoulou-Vlachou
authors.forename: A
authors.initials: A
authors.lastname: Tordai
authors.forename: M K
authors.initials: MK
authors.lastname: Viken
authors.forename: S
authors.initials: S
authors.lastname: Wenda
authors.forename: J M
authors.initials: JM
authors.lastname: Nunes
authors.forename: A
authors.initials: A
authors.lastname: Sanchez-Mazas
authors.forename: J-M
authors.initials: JM
authors.lastname: Tiercy
mesh_terms: D000483:Alleles; D046148:Donor Selection; D005060:Europe; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D015235:HLA-B Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D019520:Living Donors; D008297:Male
chemical_list: D015235:HLA-B Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen
keywords: B*44:02/44:27; DRB1*14:01/14:54; European populations; human leukocyte antigen ambiguities; human leukocyte antigen incompatibilities