engleski

4th field resolution typing is critical for defining the HLA haplotype structure

The development of next-generation sequencing (NGS)for HLA typing has already had an impact on the scope and precision of HLA research. The distinctive allelic and haplotypic diversity found at the 4thfield reveals a high level of heterozygosity and specific haplotypic associations that were not apparent at the 2ndfield. In this study, allelic resolution HLA typing was obtained for 644 individuals from Croatia. The analysis was done for most common HLA-B~C and DRB1~DQB1 associations in order to examine whether specific haplotypes are formed depending on the 4thfield typing result. Allele HLA-B*08:01 revealed two predominant haplotypes: HLA-B*08:01:01:01~C*07:01:01:01 in 92 cases (100%) and B*08:01:01:02~C*07:02:01:01 in 6 cases (85.71%). For the allele HLA-B*44:02, three specific haplotypes are observed: HLA- B*44:02:01:01~C*05:01:01:01 (44/58 ; 75.86%), B*44:02:01:01~C*16:04:01:01 (14/58 ; 24.14%)and B*44:02:01:03~C*07:04:01:01 (5/5 ; 100%). Allele HLA-B*18:01:01:02 forms haplotypes with HLA-C*07:01:01:01 (45/76 ; 59.21%) and C*12:03:01:01 (25/76 ; 32.89%) while HLA- B*18:01:01:01 comes in a haplotype with C*05:01:01:01 (5/5 ; 100%). Alleles HLA-B*27:02 and B*27:05 most commonly form haplotypes with allele HLA-C*02:02, but this study showed that allele HLA-B*27:02:01:01 forms haplotype with HLA- C*02:02:02:03(15/15 ; 100%) while HLA-B*27:05:02:01 comes mostly with HLA-C*02:02:02:01 (39/54 ; 72.22%). For the HLA-DRB1~DQB1 associations the most remarkable example was seen for HLA- DRB1*13:02 which forms haplotype with either HLA- DQB1*06:04 or DQB1*06:09 but at 4thfield level haplotypes are HLA- DRB1*13:02:01:02~DQB1*06:04:01:01 (45/45 ; 100%) and HLA-DRB1*13:02:01:01~DQB1*06:09:01:01 (13/15 ; 86.67%). There-fore, this level of resolution obtained by NGS allows studying in detail the HLA diversity and may contribute as a useful reference source for future population studies, HLA-disease association studies and for improving donor recruitment strategies of bone marrow registries.

HLA, NGS, haplotypes

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