Complete sequences of six major histocompatibility complex haplotypes, including all the major MHC class II structures.

Autor: Houwaart T; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Scholz S; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Pollock NR; Department of Biomedical Informatics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA.; Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA., Palmer WH; Department of Biomedical Informatics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA.; Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA., Kichula KM; Department of Biomedical Informatics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA.; Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA., Strelow D; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Le DB; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Belick D; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Hülse L; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Lautwein T; Biologisch-Medizinisches-Forschungszentrum (BMFZ), Genomics & Transcriptomics Laboratory, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Wachtmeister T; Biologisch-Medizinisches-Forschungszentrum (BMFZ), Genomics & Transcriptomics Laboratory, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Wollenweber TE; Biologisch-Medizinisches-Forschungszentrum (BMFZ), Genomics & Transcriptomics Laboratory, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Henrich B; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Köhrer K; Biologisch-Medizinisches-Forschungszentrum (BMFZ), Genomics & Transcriptomics Laboratory, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Parham P; Department of Structural Biology, and Department of Microbiology and Immunology, Stanford University, Stanford, California, USA., Guethlein LA; Department of Structural Biology, and Department of Microbiology and Immunology, Stanford University, Stanford, California, USA., Norman PJ; Department of Biomedical Informatics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA.; Department of Immunology and Microbiology, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA., Dilthey AT; Institute of Medical Microbiology and Hospital Hygiene, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Jazyk: angličtina
Zdroj: HLA [HLA] 2023 Jul; Vol. 102 (1), pp. 28-43. Date of Electronic Publication: 2023 Mar 18.
DOI: 10.1111/tan.15020
Abstrakt: Accurate and comprehensive immunogenetic reference panels are key to the successful implementation of population-scale immunogenomics. The 5Mbp Major Histocompatibility Complex (MHC) is the most polymorphic region of the human genome and associated with multiple immune-mediated diseases, transplant matching and therapy responses. Analysis of MHC genetic variation is severely complicated by complex patterns of sequence variation, linkage disequilibrium and a lack of fully resolved MHC reference haplotypes, increasing the risk of spurious findings on analyzing this medically important region. Integrating Illumina, ultra-long Nanopore, and PacBio HiFi sequencing as well as bespoke bioinformatics, we completed five of the alternative MHC reference haplotypes of the current (GRCh38/hg38) build of the human reference genome and added one other. The six assembled MHC haplotypes encompass the DR1 and DR4 haplotype structures in addition to the previously completed DR2 and DR3, as well as six distinct classes of the structurally variable C4 region. Analysis of the assembled haplotypes showed that MHC class II sequence structures, including repeat element positions, are generally conserved within the DR haplotype supergroups, and that sequence diversity peaks in three regions around HLA-A, HLA-B+C, and the HLA class II genes. Demonstrating the potential for improved short-read analysis, the number of proper read pairs recruited to the MHC was found to be increased by 0.06%-0.49% in a 1000 Genomes Project read remapping experiment with seven diverse samples. Furthermore, the assembled haplotypes can serve as references for the community and provide the basis of a structurally accurate genotyping graph of the complete MHC region.
(© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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