High‐Resolution (4th‐Field) NGS ‐Based HLA Allele and Haplotype Frequencies in a Western Central Anatolian Turkish Population
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2026
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| _version_ | 1867002629742133249 |
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| author | Emel Yantır |
| author_facet | Emel Yantır Emel Yantır |
| collection | Wiley Open Access |
| contents | High‐Resolution (4th‐Field) NGS ‐Based HLA Allele and Haplotype Frequencies in a Western Central Anatolian Turkish Population Emel Yantır HLA ABSTRACT This study presents the first 4th‐field high resolution HLA allele and multi‐locus haplotype frequencies from a regional cohort in Western Central Anatolia, including Eskişehir and its surrounding provinces, providing new insights into Turkiye's genetic diversity. Next‐generation sequencing (NGS) was used to genotype 138 unrelated healthy individuals for six HLA loci: ‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1. MIA FORA NGS FLEX platform was used for genotyping and population genetic analyses were primarily conducted using the HLA‐net GENE[RATE] pipeline, with PyPop applied for complementary analyses. Fifty‐four HLA‐A, 96 HLA‐B, 62 HLA‐C, 74 DRB1, 45 DQB1 and 33 DPB1 alleles were found at the 4th‐field level. A*24:02:01:01 (15.5%), B*51:01:01:01 (6.9%), C*06:02:01:01 (8.7%), DRB1*11:04:01:01 (10.8%), DQB1*03:01:01:02 (18.5%) and DPB1*04:01:01:01 (17.7%) were the most common alleles. The study also identified several rare alleles and haplotypes. This finding highlights the significance of 4th‐field resolution in revealing fine‐scale diversity. Haplotype analyses observed population‐specific combinations with strong linkage disequilibrium, especially between DRB1 and DQB1 (D′ = 0.9702). All reported multi‐locus haplotypes were validated through significant pairwise LD (standardised residual > 2) between neighbouring loci. For instance, the LD‐supported haplotype A*01:01:01:01 ~ B*08:01:01 ~ DRB1*03:01:01:01 (1.45%) . When compared to lower‐field (2nd‐field) data, a considerable amount of sub‐allelic diversity was obscured. These results underline the significance of high‐resolution HLA genotyping for clinical and population‐based applications, as well as Türkiye's distinct immunogenetic structure as a genetic bridge connecting Europe, Asia and the Middle East. 10.1111/tan.70613 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/tan.70613 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_tan_70613 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | High‐Resolution (4th‐Field) NGS ‐Based HLA Allele and Haplotype Frequencies in a Western Central Anatolian Turkish Population Emel Yantır HLA High‐Resolution (4th‐Field) NGS ‐Based HLA Allele and Haplotype Frequencies in a Western Central Anatolian Turkish Population Emel Yantır HLA ABSTRACT This study presents the first 4th‐field high resolution HLA allele and multi‐locus haplotype frequencies from a regional cohort in Western Central Anatolia, including Eskişehir and its surrounding provinces, providing new insights into Turkiye's genetic diversity. Next‐generation sequencing (NGS) was used to genotype 138 unrelated healthy individuals for six HLA loci: ‐A, ‐B, ‐C, ‐DRB1, ‐DQB1 and ‐DPB1. MIA FORA NGS FLEX platform was used for genotyping and population genetic analyses were primarily conducted using the HLA‐net GENE[RATE] pipeline, with PyPop applied for complementary analyses. Fifty‐four HLA‐A, 96 HLA‐B, 62 HLA‐C, 74 DRB1, 45 DQB1 and 33 DPB1 alleles were found at the 4th‐field level. A*24:02:01:01 (15.5%), B*51:01:01:01 (6.9%), C*06:02:01:01 (8.7%), DRB1*11:04:01:01 (10.8%), DQB1*03:01:01:02 (18.5%) and DPB1*04:01:01:01 (17.7%) were the most common alleles. The study also identified several rare alleles and haplotypes. This finding highlights the significance of 4th‐field resolution in revealing fine‐scale diversity. Haplotype analyses observed population‐specific combinations with strong linkage disequilibrium, especially between DRB1 and DQB1 (D′ = 0.9702). All reported multi‐locus haplotypes were validated through significant pairwise LD (standardised residual > 2) between neighbouring loci. For instance, the LD‐supported haplotype A*01:01:01:01 ~ B*08:01:01 ~ DRB1*03:01:01:01 (1.45%) . When compared to lower‐field (2nd‐field) data, a considerable amount of sub‐allelic diversity was obscured. These results underline the significance of high‐resolution HLA genotyping for clinical and population‐based applications, as well as Türkiye's distinct immunogenetic structure as a genetic bridge connecting Europe, Asia and the Middle East. 10.1111/tan.70613 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | High‐Resolution (4th‐Field) NGS ‐Based HLA Allele and Haplotype Frequencies in a Western Central Anatolian Turkish Population |
| topic | HLA |
| url | https://onlinelibrary.wiley.com/doi/10.1111/tan.70613 |