Sequence of four new HLA‐Cw alleles: a possible role of interallelic recombination

Abstract

In order to extend our current understanding of HLA-C polymorphism, four new alleles have been cloned and sequenced: Cw*1801 in a donor of mixed origin, Cw*02024 in a Senegalese individual, Cw*1205 and Cw*1604 in European Caucasoid blood donors. HLA-Cw*1801, which most likely results from an interallelic recombination between Cw*0704 and 0401 alleles, was not associated with B*8101, but with either B*4403 or B18. The Cw*02024 allele differs from Cw*02022 by a silent mutation in exon 3. Both Cw*1801 and Cw*02024 appear to be rather frequent in populations of African origin but have not yet been detected in Caucasoids. HLA-Cw*1604 differs from Cw*1601 by two nucleotides at codon 156 leading to a Gln to Trp substitution. This new Cw16 subtype was subsequently identified in three additional unrelated families, all of South-European origin, and presented an unusual association with B*4402 in all cases. HLA-Cw*1205 is a composite allele with the alpha1 domain of Cw*1602 and the alpha2 domain of Cw*1203. It appears to be rare, at least in European Caucasoids. Three of these four alleles may have resulted from gene conversion-like or interallelic recombination events.

Recognition of the three deduced probable HLA haplotypes that are associated with HLA-C∗16:04:01 (A∗33:03-B∗44:02-C∗16:04:01-DRB1∗11:04:01 and A∗24-B∗44:02-C∗16:04:01-DRB1∗11:04) and HLA-B∗15:109 (A∗11-B∗15:109-DRB1∗04) in Taiwanese unrelated hematopoietic stem cell donors

“…Taken all together, two HLA-A, HLA-B, HLA-C, and HLA-DRB1 haplotypes may be deduced and these are A*33:03-B*44:02-C*16:04:01-DRB1*11:04 and A*24-B*44:02-C*16:04:01-DRB1*11:04. Because the haplotype A*24-B*44:02-C*16:04:01-DRB1*11:04 was initially found in an Italian individual [7], we assume this C*16:04:01 associated HLA haplotype is a European and Oriental haplotype, whereas the haplotype A*33:03-B*44:02-C*16:04:01-DRB1*11:04 is an Asian haplotype. In addition, it is apparent that C*16:04:01 is in linkage with B*44:02 and DRB1*11:04, because all donors bearing C*16:04:01 also carry B*44:02 and DRB1*11:04 (Table 1).…”

“…C*16:04:01 was initially detected in a family from south Italy and subsequently found in three unrelated Mediterranean Caucasoid donors [7]. C*16:04: 01 could possibly result from a gene conversion-like recombination event involving C*16:01 as recipient and any one of the Trp 156-positive alleles (C*02, C*06 and C*12) as donor [7].…”

“…C*16:04:01 was initially detected in a family from south Italy and subsequently found in three unrelated Mediterranean Caucasoid donors [7]. C*16:04: 01 could possibly result from a gene conversion-like recombination event involving C*16:01 as recipient and any one of the Trp 156-positive alleles (C*02, C*06 and C*12) as donor [7]. We deduced two most probable C*16:04:01 associated HLA haplotypes from our unrelated bone marrow donors, one of which, (A*24-B*44:02-C*16:04:01-DRB1*11:04), is a European and Asian haplotype, and was also identified in an Italian individual as reported by Grundschober et al [7].…”

Associations of HLA-C Alleles With Multinodular Goiters

“…This allele can only be detected by molecular biological tech- niques, and some of its subtypes have been described in recent years. 43 This justifies the few articles in which it has been described, but among the few associations described for this allele are those that link it with Behçet disease, 44 acquired immunodeficiency syndrome, 45 and melanoma. 46,47 Therefore, further studies of goiter could be of wider interest.…”

Outcome of unrelated bone marrow donor searches in 174 children resulting in 45 patients transplanted in the HLA-matched and -mismatched situation

“…Rare alleles found in the retrospective study were sequenced after cloning by using either manual sequencing or automated fluorescence methods. [22][23][24] All alleles from class I and class II which have been published in the nomenclature for factors of the HLA system were studied. 25 The mixed lymphocyte culture (MLC) was carried out for each patient/donor pair and used as a tool for donor selection.…”