HLAIb worldwide genetic diversity: New HLA-H alleles and haplotype structure description

Paganini, Julien; Abi-Rached, Laurent; Gouret, Philippe; Pontarotti, Pierre; Chiaroni, Jacques; Cristofaro, Julie Di

doi:10.1016/j.molimm.2019.04.017

Cited by 15 publications

(26 citation statements)

References 64 publications

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“…In comparison, the two most common E*01:03 alleles ( E*01:03:02:01 and E*01:03:01:01 ) have a combined frequency of 87.5% and a total of 12 E*01:03 alleles were observed (Figure 1). Interestingly the third most frequent HLA‐E protein variant observed was E*01:06 (1.7%) (Figure 1), this allele had only been submitted once to the IPD‐IMGT/HLA Database and previous studies have detected it at lower frequencies of 0.6‐0.8% 5‐7,36,37 . The higher frequency of E*01:06 observed here is likely due to our full‐gene coverage, allowing detection of the E*01:06 defining SNP 1857C>T in exon 4, whereas previous studies were largely restricted to sequencing exons 2 and 3.…”

Section: Figurementioning

confidence: 58%

Single molecule real‐time DNA sequencing of the full HLA‐E gene for 212 reference cell lines

Lucas

Hayhurst

Turner

et al. 2020

HLA

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We have developed a genotyping assay that produces fully phased, unambiguous HLA-E genotyping using Pacific Biosciences' single molecule real-time DNA sequencing. In total 212 cell lines were genotyped, including the panel of 107 established at the 10th International Histocompatibility Workshop. Our results matched the previously known HLA-E genotype in 94 (44.3%) cell lines, in all cases either improving or equalling previous genotyping resolution. Three (1.4%) cells had discrepant HLA-E genotyping data and 115 (54.2%) had no previous HLA-E data. The HLA-E genotypes for four (1.9%) cell lines resulted in a change of zygosity by identifying two distinct haplotypes. We discovered eight novel HLA-E alleles, extended the known reference sequence of seven and confirmed the existence of a further 10.

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Section: Figurementioning

confidence: 58%

Single molecule real‐time DNA sequencing of the full HLA‐E gene for 212 reference cell lines

Lucas

Hayhurst

Turner

et al. 2020

HLA

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“…RNA sequencing data were analyzed using PolyPheMe software specially designed for HLA NGS data analysis (Xegen, France) for which accuracy was assessed at 99.3% (10,32,33). This software is based on a specific strategy to avoid bias raised by the use of a unique genome as a reference for HLA NGS data mapping (34)(35)(36).…”

Section: Hla-h Transcriptional Expression In Cell Line From the 1000 mentioning

confidence: 99%

“…Then, all reads assigned to HLA class I were filtered out for their specificity for HLA Ia (A, B, C), Ib (E, F, G), and pseudogenes that showed the highest homology with HLA-H. Lastly, remaining reads were selected for their specificity for HLA-H using all exon sequences. The analysis was based on the 25 HLA-H alleles described in the IPD-IMGT/HLA database 3.37.0 (30), including the new alleles described in (10).…”

Section: Hla-h Transcriptional Expression In Cell Line From the 1000 mentioning

confidence: 99%

“…In a previous study, we identified 13 novel HLA-H alleles, which showed unexpected genetic diversity, with a total of 25 second-field alleles (10). Among these, H * 02:07 and H * 02:14 potentially encode complete transmembrane HLA proteins; while the H * 02:14 allelic frequency was very low, H * 02:07 displayed global worldwide frequencies of 8.6% that reached 19.6% in East Asian populations (10).…”

Section: Introductionmentioning

confidence: 96%

“…HLA-H was defined as a non-functional gene because of its deletion from chromosomes carrying HLA-A * 23/ * 24 alleles (6)(7)(8)(9)(10)(11), but also because its amino acid sequence predicted a potentially non-functional truncated protein.…”

Section: Introductionmentioning

confidence: 99%

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HLA-H: Transcriptional Activity and HLA-E Mobilization

et al. 2020

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Little attention is paid to pseudogenes from the highly polymorphic HLA genetic region. The pseudogene HLA-H is defined as a non-functional gene because it is deleted at different frequencies in humans and because it encodes a potentially non-functional truncated protein. However, different studies have shown HLA-H transcriptional activity. We formerly identified 13 novel HLA-H alleles, including the H * 02:07 allele, which reaches 19.6% in East Asian populations and encodes a full-length HLA protein. The aims of this study were to explore the expression and possible function of the HLA-H molecule. HLA-H may act as a transmembrane molecule and/or indirectly via its signal peptide by mobilizing HLA-E to the cell surface. We analyzed HLA-H RNA expression in Peripheral Blood Mononuclear Cells (PBMC), Human Bronchial Epithelial Cells (HBEC), and available RNA sequencing data from lymphoblastoid cell lines, and we looked to see whether HLA-E was mobilized at the cell surface by the HLA-H signal peptide. Our data confirmed that HLA-H is transcribed at similar levels to HLA-G. We characterized a hemizygous effect in HLA-H expression, and expression differed according to HLA-H alleles; most interestingly, the HLA-H * 02:07 allele had the highest level of mRNA expression. We showed that HLA-H signal peptide incubation mobilized HLA-E molecules at the cell surface of T-Lymphocytes, monocytes, B-Lymphocytes, and primary epithelial cells. Our results suggest that HLA-H may be functional but raises many biological issues that need to be addressed.

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The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma

Ormandjieva

Yordanov²,

Stoyanov

et al. 2023

Mol Biol Rep

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Background:Laryngeal cancer is one of the most common head and neck malignancies worldwide.Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. LSCC originates from the epidermal keratinocytes and is characterized by impaired keratinization. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chainrelated MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chainrelated MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC.Materials and methods:In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 68 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx).Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. Results:The HLA disease association tests revealed a statistically signi cant predisposing association of HLA-F*01:01:02 (P=0.0103, OR=24.0194) with LSCC, while HLA-F*01:01:01 (P=8.21e-04, OR=0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically signi cant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P=0.0054, haplotype score=-2.7801). Conclusion:Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of development of LSCC.

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HLAIb worldwide genetic diversity: New HLA-H alleles and haplotype structure description

Cited by 15 publications

References 64 publications

Single molecule real‐time DNA sequencing of the full HLA‐E gene for 212 reference cell lines

Single molecule real‐time DNA sequencing of the full HLA‐E gene for 212 reference cell lines

HLA-H: Transcriptional Activity and HLA-E Mobilization

The role of non-classical and chain-related human leukocyte antigen polymorphisms in laryngeal squamous cell carcinoma

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