Dataset Information

Characterization of a novel HLA-A11:335 allele resulting from a rare interlocus recombination involving HLA-A11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

ABSTRACT: The major histocompatibility complex (MHC) in humans includes three classical class I loci (A, B, and C), which are important biomarkers for the transplantation of organs and hematopoietic stem cells. In the MHC, polymorphism is known to be extremely high while interlocus recombination is rare. We report a rare interlocus recombination between HLA-A and HLA-H, which was analyzed using next generation sequencing and nanopore sequencing. In the sample, the genotypes of HLA-A, B, C, DRB1, and DQB1 were firstly determined using the methods of sequence-specific primer, sequence-specific oligonucleotide, Sanger's sequencing, and NGS; however, HLA-A could not be phased. Nanopore sequencing was finally utilized to distinguish the sequence of the novel allele. Finally, the novel HLA-A*11:335 allele was identified as an interlocus recombination involving HLA-A*11:01:01:01/126 and HLA-H*02:07/14/18 alleles; this was mainly achieved by nanopore sequencing. The identification of the interlocus recombination indicated that nanopore sequencing can be helpful in the characterization of novel alleles with complex rearrangements. Interlocus recombination has been identified as one of the mechanisms involved in the generation of novel HLA alleles.

SUBMITTER: Zhang LQ

PROVIDER: S-EPMC8925214 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Characterization of a novel HLA-A11:335 allele resulting from a rare interlocus recombination involving HLA-A11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

Zhang Li-Qun LQ Rozemuller Erik E Wang Dan D Liu Xiang-Jun XJ Cai Jian-Ping JP

BMC medical genomics 20220316 1

<h4>Background</h4>The major histocompatibility complex (MHC) in humans includes three classical class I loci (A, B, and C), which are important biomarkers for the transplantation of organs and hematopoietic stem cells. In the MHC, polymorphism is known to be extremely high while interlocus recombination is rare. We report a rare interlocus recombination between HLA-A and HLA-H, which was analyzed using next generation sequencing and nanopore sequencing.<h4>Methods</h4>In the sample, the genotyp ...[more]

PMID: 35296321

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction model for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February-August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27-3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24-3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50-7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01-1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31-6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A*11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article that describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.

Dataset Information

Characterization of a novel HLA-A11:335 allele resulting from a rare interlocus recombination involving HLA-A11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

Publications

Characterization of a novel HLA-A11:335 allele resulting from a rare interlocus recombination involving HLA-A11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

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Dataset Information

Characterization of a novel HLA-A*11:335 allele resulting from a rare interlocus recombination involving HLA-A*11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

Publications

Characterization of a novel HLA-A*11:335 allele resulting from a rare interlocus recombination involving HLA-A*11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Characterization of a novel HLA-A11:335 allele resulting from a rare interlocus recombination involving HLA-A11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.

Characterization of a novel HLA-A11:335 allele resulting from a rare interlocus recombination involving HLA-A11:01:01:01/126 and HLA-H*02:07/14/18 alleles with nanopore sequencing, in a volunteer from the China Marrow Donor Program.