scholarly journals Identification of the Novel HLA-A*11:335 Allele, a Rare Interlocus Recombination Involving HLA-A*11:01:01:01 and HLA-H*02:07/14/18 Alleles With Nanopore Sequencing, in a Volunteer From the China Marrow Donor Program

2021 ◽  
Author(s):  
Li-Qun Zhang ◽  
Erik Rozemuller ◽  
Dan Wang ◽  
Xiang-Jun Liu ◽  
Jian-Ping Cai
Keyword(s):  
Hla Typing ◽  
Nanopore Sequencing ◽  
The Novel ◽  
Specific Primer ◽  
Hematopoietic Stem ◽  
Classical Class ◽  
Histocompatibility Complex ◽  
Mhc Polymorphism ◽  
Primer Sequence ◽  
Generation Sequencing

Abstract Background: The major histocompatibility complex in humans includes three classical class I loci (A, B and C), which are important biomarkers for transplant 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. Results: In the sample, the genotypes of HLA-A, B, C, DRB1 and DQB1 were firstly phased with 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 and HLA-H*02:07/14/18 alleles; this was mainly achieved by nanopore sequencing. Conclusions: The identification of the interlocus recombination indicated that nanopore sequencing may be the most precise method for HLA typing. Interlocus recombination has been identified as one of the mechanisms involved in the generation of novel HLA alleles.

P013 Role of next generation sequencing in HLA typing of hematopoietic stem cell transplant patients: Two case reports

2019 ◽  
Vol 80 ◽  
pp. 63
Author(s):  
Tiffany R. Baker ◽  
Susana O. Infante ◽  
Eric D. Garabiles ◽  
Rodrigo O. Santiago ◽  
Yuri L. Robinson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Case Reports ◽  
Hla Typing ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Transplant Patients ◽  
Generation Sequencing

scholarly journals HLA diversity in the Russian population assessed by next generation sequencing

2021 ◽  
Vol 23 (3) ◽  
pp. 509-522
Author(s):  
E. G. Khamaganova ◽  
E. A. Leonov ◽  
A. R. Abdrakhimova ◽  
S. P. Khizhinskiy ◽  
T. V. Gaponova ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Association Studies ◽  
Reference Sample ◽  
Allelic Diversity ◽  
Russian Population ◽  
Hla Typing ◽  
Next Generation ◽  
Hematopoietic Stem ◽  
Hla Alleles ◽  
Generation Sequencing

Next generation sequencing is used to determine full-length sequences of HLA genes at the 4-field (allelic) resolution. The study was aimed at determining frequency and diversity of HLA alleles in a cohort of blood donors from the Registry of the National Research Center for Hematology who design ated themselves as Russians (including some not routinely typed variations in HLA gene regions). The studied population consisted of 1510 donors. HLA typing was performed by next generation sequencing. Libraries were performed with AllType NGS Amplification Kits (One Lambda, USA) and sequenced using MiSeq (Illumina, USA). Data analysis used the TypeStream Visual Software V2.0.0.68 (One Lambda, USA) and IPD-IMGT/HLA database 3.40.0.1. Arlequin 3.5 software was used for estimation of allele and haplotype frequencies, deviation from Hardy-Weinberg equilibrium. 82 HLA-A, 156 HLA-В and 85 HLA-С alleles were identified with four-field resolution. 45 HLA-DRB1 and 18 HLA-DQB1 alleles were identified with 2-3-field resolution. Considerable HLA diversity was found among the donors self-designated as Russians: the population had large numbers of distinct alleles at each HLA gene, high percentage of alleles (25-32% of HLA class I) were revealed only once. Sufficient numbers of new alleles were registered which are absent in the IPD-IMGT/HLA database. Considerable allelic diversity in Russian population is due to low-incidence alleles. Despite this diversity, the majority of HLA alleles detected at each locus were common. Significant HLA diversity of the donors was connected with a large number of alleles with rare occurrence. The novel alleles identified in our study differed from the known alleles by single nucleotide substitutions. The most common alleles at the four-field level were as follows: A*02:01:01:01 (27.1%), C*07:02:01:03 (13.1%), A*03:01:01:01 (13.0%), B*07:02:01:01 (13.0%), A*01:01:01:01 (11.6%) and C*07:01:01:01/16 (10.4%). The HLA alleles, which are common for Russian populations, are not always common or well-documented alleles in present catalogues. The data obtained in this study may be used as a reference sample for estimation of HLA allele frequencies in Russian population, for proper frequency evaluation of specific alleles when searching donors for allogeneic hematopoietic stem cell transplantation, as well as for association studies between HLA alleles and different diseases, and for research in population genetics.

scholarly journals Ancient interlocus exon exchange in the history of the HLA-A locus.

Genetics ◽  
1989 ◽  
Vol 122 (3) ◽  
pp. 681-686 ◽  
Author(s):  
A L Hughes ◽  
M Nei
Keyword(s):  
Major Histocompatibility Complex ◽  
Present Finding ◽  
Evolutionary Process ◽  
Class I ◽  
Hybrid Gene ◽  
Classical Class ◽  
Histocompatibility Complex ◽  
History Of ◽  
Mhc Polymorphism ◽  
Nonclassical Class

Abstract The major histocompatibility complex (MHC) in humans and chimpanzees includes three classical class I loci, A, B and C, which encode glycoproteins expressed on the surface of all nucleated cells. There are also several nonclassical class I loci including E, which have more limited expression. By analyzing published sequences, we have shown that in exons 4 and 5, A locus alleles from both humans and chimpanzees are much more similar to E than to B or C alleles, whereas in exons 2 and 3 alleles from all three classical class I loci are much more similar to each other than any one is to E. We propose that some 20 million years ago, interlocus recombination led to the formation of a hybrid gene in which exons 2 and 3 were derived from the original A locus and exons 4 and 5 were derived from the E locus. The fact that such an ancient event can still be detected suggests that interlocus recombination is rare in the MHC and does not significantly contribute to MHC polymorphism, which is known to be extremely high. The present finding, however, supports Gilbert's idea that exons in a gene may occasionally be replaced by those from another gene in the evolutionary process.

Characterization of the novel HLA‐C *07:944 allele by next‐generation sequencing

HLA ◽  
2021 ◽  
Author(s):  
Maria Loginova ◽  
Olga Makhova ◽  
Daria Smirnova ◽  
Igor Paramonov ◽  
Maksim Zarubin
Keyword(s):  
Next Generation Sequencing ◽  
The Novel ◽  
Next Generation ◽  
Generation Sequencing

scholarly journals Myelodysplastic Syndromes in the Postgenomic Era and Future Perspectives for Precision Medicine

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3296
Author(s):  
Ioannis Chanias ◽  
Kristina Stojkov ◽  
Gregor Stehle ◽  
Michael Daskalakis ◽  
Helena Simeunovic ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Myelodysplastic Syndromes ◽  
Clonal Evolution ◽  
Driver Mutations ◽  
Future Perspectives ◽  
Hematopoietic Stem ◽  
Secondary Acute Myeloid Leukemia ◽  
Stem And Progenitor Cells ◽  
Unfit Patients ◽  
Generation Sequencing

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal disorders caused by sequential accumulation of somatic driver mutations in hematopoietic stem and progenitor cells (HSPCs). MDS is characterized by ineffective hematopoiesis with cytopenia, dysplasia, inflammation, and a variable risk of transformation into secondary acute myeloid leukemia. The advent of next-generation sequencing has revolutionized our understanding of the genetic basis of the disease. Nevertheless, the biology of clonal evolution remains poorly understood, and the stochastic genetic drift with sequential accumulation of genetic hits in HSPCs is individual, highly dynamic and hardly predictable. These continuously moving genetic targets pose substantial challenges for the implementation of precision medicine, which aims to maximize efficacy with minimal toxicity of treatments. In the current postgenomic era, allogeneic hematopoietic stem cell transplantation remains the only curative option for younger and fit MDS patients. For all unfit patients, regeneration of HSPCs stays out of reach and all available therapies remain palliative, which will eventually lead to refractoriness and progression. In this review, we summarize the recent advances in our understanding of MDS pathophysiology and its impact on diagnosis, risk-assessment and disease monitoring. Moreover, we present ongoing clinical trials with targeting compounds and highlight future perspectives for precision medicine.

Characterization of the novel HLA‐B *51:296 allele by next‐generation sequencing

HLA ◽  
2020 ◽  
Author(s):  
Steve Genebrier ◽  
Vincent Elsermans ◽  
Emeric Texeraud ◽  
Gerald Bertrand ◽  
Virginie Renac
Keyword(s):  
Next Generation Sequencing ◽  
The Novel ◽  
Next Generation ◽  
Generation Sequencing
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