Naslov
Next-generation sequencing reveals and validates HLA polymorphism among Croatians

Autori
Maskalan, Marija ; Grubić, Zorana ; Štingl Janković, Katarina ; Burek Kamenarić, Marija ; Jukić, Lucija ; Žunec, Renata

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
EFI Abstracts Oral and Posters / - : John Wiley & Sons, 2023, 328-428

Skup
Joint 36th European Immunogenetics and Histocompatibility Conference

Mjesto i datum
Nantes, Francuska, 26.04.2023. - 29.04.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
NGS, HLA, polymorphism, Croatians

Sažetak
Implementation of next generation sequencing (NGS) in routine clinical HLA laboratory typing brings numerous information but also challenges in data analysis. First 1268 samples, typed in our Tissue Typing Centre at University Hospital Centre Zagreb, with NGSgo-MX6-1 (GenDx) for HLA-A, B, C, DRB1, DQB1 and DPB1 loci revealed 19 novel HLA alleles. Among them, 9 (47.4%) were single amino acid substitution variants when compared to the most similar allele (HLA-A*01:200, A*02:836, A*02:1079, B*08:251, B*18:169, B*40:517, C*04:477, C*05:276 and DPB1*1146:01). Four alleles (HLA- B*15:18:08, B*18:37:02, B*27:02:06 and C*12:03:80) had silent substitution with no change in amino acid sequence and remaining six alleles (31.6%) showed only intronic mismatches to their most similar allele (HLA-A*03:01:01:112, A*11:01:01:44, A*11:01:01:83, B*07:02:01:107, B*08:01:01:67 and C*05:46:01:02). Most of the novel alleles were found at the HLA class I loci since the used tests cover the entire HLA-A, B and C genes. Class II loci are covered for exons 2 and 3 for HLA-DRB1 and DQB1, and exons 2-5 for HLA-DPB1. Besides these novel alleles, additional 102 alleles were observed only once. Looking at their status in the CIWD catalogue (version 3.0.0.), compiled from more than 8 million individuals, 46 alleles were common (≥1 in 10 000), 13 were intermediate (≥1 in 100 000), 16 were well-documented (≥5 occurrences) and 27 alleles were rare (not-CIWD). This diversity emphasizes the importance of continued research for identifying and publishing these alleles, not only to improve donor/recipient matching in hematopoietic stem cell transplantation program, but also to allow us to study in detail the HLA population diversity and mechanisms in which different demographic events and selective pressures have shaped HLA profiles of various populations.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Kliničke medicinske znanosti

POVEZANOST RADA