Characterization of the novel <i>HLA‐DRB1*03:147</i> allele by sequencing‐based typing

Ralazamahaleo, Mamy; Elsermans, Vincent; Top, Isabelle; Guidicelli, Gwendaline; Visentin, Jonathan

doi:10.1111/tan.13419

Cited by 6 publications

(2 citation statements)

References 2 publications

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“…The "Mismatch in exon" warning was observed for 43 (0.7%) alleles, representing 1.9% of all warnings (43/2324). Following sequence review, 11 of these were considered probably new, of which nine were confirmed by re-typing and were referenced, [37][38][39][40][41][42][43][44][45] and two had already been described in the IPD-IMGT/HLA database. The other 32 exon mismatches were not considered new alleles because of homopolymers (15/43), high background (1/43), low read depth (9/43), or phasing anomalies (7/43) ( Table 1).…”

Section: F I G U R E 1 Description Of Thementioning

confidence: 99%

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

Cargou

Ralazamahaleo

Blouin

et al. 2019

HLA

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HLA genotyping by next‐generation sequencing is now widely performed. We aimed at evaluating the performance of the One Lambda AllType kit using Thermo Fisher Scientific reagents on the Ion S5 XL platform. Reads were analyzed using the TypeStream Visual software. We performed 15 runs between April and September 2018 to type DNA at the HLA‐A/B/C/DRB1/3/4/5/DQA1/DQB1/DPA1/DPB1 loci from 340 samples and 15 positive controls. We observed only seven (0.1%) critical mistakes among the 6009 alleles typed, corresponding to two allele dropouts, one false heterozygous typing assignment, and four phasing abnormalities. Among the 1793 presumably new alleles detected by the analysis software, 11 displayed exon mismatches, of which nine were confirmed as new alleles and two had been described previously. Intron mismatches were observed among the remaining presumably new alleles, of which 371 were considered as probably new, and 1411 were rejected for at least one sequence feature such as homopolymers (n = 1206), nucleotide doublet repeats (n = 26), low read depth (<200 reads, n = 93), high background (>20%, n = 79), or phasing abnormalities (n = 7). A comparison of the AllType results with those obtained using other methods at the second‐field resolution level showed 99.5% (1497/1504) concordance for the HLA‐A/B/C/DRB1/DQB1/DPB1 loci. Similar agreement was observed between the HLA‐C or HLA‐DRB3/4/5 results and common linkage disequilibrium, with 96.6% (657/680) and 97.2% (530/545) concordance, respectively. Therefore, the AllType kit used with the Ion S5 XL platform displayed satisfactory performance for HLA typing in current clinical practice.

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Section: F I G U R E 1 Description Of Thementioning

confidence: 99%

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

Cargou

Ralazamahaleo

Blouin

et al. 2019

HLA

Self Cite

143

139

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“…The particular allele that was found to explain the association signal in the HLA region (HLA-DRB1*03:147 [92], has only recently been reported and so there is limited information about functionality. Associations of this allele with other GWAS loci should be interpreted with caution given the high LD across the region.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

Packer

Shrine

Hall

et al. 2022

Preprint

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Background Chronic sputum production impacts on quality of life and is a feature of many respiratory diseases. Identification of the genetic variants associated with chronic sputum production in a disease agnostic sample could improve understanding of its causes and identify new molecular targets for treatment. Methods We conducted a genome-wide association study (GWAS) of chronic sputum production in UK Biobank. Signals meeting genome-wide significance (P<5x10-8) were fine-mapped and putative causal genes identified by gene expression analysis. GWAS of respiratory traits were interrogated to identify whether the signals were driven by existing respiratory disease amongst the cases and variants were further investigated for wider pleiotropic effects using phenome-wide association studies (PheWAS). Findings From a GWAS of 9,714 cases and 48,471 controls, we identified six novel genome-wide significant signals for chronic sputum production including the Human Leukocyte Antigen (HLA) locus, chromosome 11 mucin locus (containing MUC2, MUC5AC and MUC5B) and the FUT2 locus. The mucin locus signal had previously been reported for association with moderate-to-severe asthma. The HLA signal was fine-mapped to an amino-acid change of threonine to arginine (frequency 36.8%) in HLA-DRB1 (HLA-DRB1*03:147). The signal near FUT2 was associated with expression of several genes including FUT2, for which the direction of effect was tissue dependent. Our PheWAS identified a wide range of associations. Interpretation Novel signals at the FUT2 and mucin loci highlight mucin flucosylation as a driver of chronic sputum production even in the absence of diagnosed respiratory disease and provide genetic support for this pathway as a target for therapeutic intervention.

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HLA class II peptide-binding-region analysis reveals funneling of polymorphism in action

et al. 2021

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Characterization of the novel HLA‐DRB103:147* allele by sequencing‐based typing

Abstract: HLA‐DRB103:147 differs from HLA‐DRB103:01:01:01 by one nucleotide substitution at codon 233 in exon 5.

Cited by 6 publications

References 2 publications

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

HLA class II peptide-binding-region analysis reveals funneling of polymorphism in action

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Characterization of the novel HLA‐DRB1*03:147 allele by sequencing‐based typing

Abstract: HLA‐DRB1*03:147 differs from HLA‐DRB1*03:01:01:01 by one nucleotide substitution at codon 233 in exon 5.

Cited by 6 publications

References 2 publications

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

Evaluation of the AllType kit for HLA typing using the Ion Torrent S5 XL platform

Genome-wide association study of chronic sputum production implicates loci involved in mucus production and infection

HLA class II peptide-binding-region analysis reveals funneling of polymorphism in action

Contact Info

Product

Resources

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Characterization of the novel HLA‐DRB103:147* allele by sequencing‐based typing

Abstract: HLA‐DRB103:147 differs from HLA‐DRB103:01:01:01 by one nucleotide substitution at codon 233 in exon 5.