Defining KIR and HLA Class I Genotypes at Highest Resolution via High-Throughput Sequencing
| Autor: | Jill A. Hollenbach, Steven Norberg, Jorge R. Oksenberg, Mostafa Ronaghi, Emily E. Wroblewski, Wesley M. Marin, Paul Norman, Jacques Chiaroni, James A. Traherne, Jyothi Jayaraman, Neda Nemat-Gorgani, Lisbeth A. Guethlein, Peter Parham, Raja Rajalingam, Elham Ashouri, John Trowsdale |
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| Přispěvatelé: | Department of Physics, Chemistry and Biology [Linköping] (IFM), Linköping University (LIU), Howard Hughes Medical Institute (HHMI), Dept Pathol, Div Immunol, University of Cambridge [UK] (CAM), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Department of Neurology [San Francisco], University of California [San Francisco] (UCSF), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), Trowsdale, John [0000-0002-0150-5698], Traherne, James [0000-0002-6003-8559], Apollo - University of Cambridge Repository |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Gene Dosage Genes MHC Class I Medical and Health Sciences MHC Class I 0302 clinical medicine Receptors KIR Receptors 2.1 Biological and endogenous factors Genetics(clinical) Aetiology Genetics (clinical) ComputingMilieux_MISCELLANEOUS Genetics & Heredity Genetics Genome gene content diversity High-Throughput Nucleotide Sequencing hemic and immune systems [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology Biological Sciences KIR 3. Good health HIV/AIDS Biotechnology Human Genotype chemical and pharmacologic phenomena HLA-C Antigens Human leukocyte antigen Biology Article DNA sequencing 03 medical and health sciences Genetic otorhinolaryngologic diseases HLA-B Antigens Humans Polymorphism 1000 Genomes Project Genotyping Alleles Polymorphism Genetic HLA-A Antigens Genome Human Human Genome Haplotype HLA class I immunity Transplantation 030104 developmental biology Genes Haplotypes Human genome highly polymorphic 030215 immunology |
| Zdroj: | American Journal of Human Genetics American Journal of Human Genetics, Elsevier (Cell Press), 2016, 99 (2), ⟨10.1016/j.ajhg.2016.06.023⟩ American Journal of Human Genetics, 2016, 99 (2), ⟨10.1016/j.ajhg.2016.06.023⟩ American journal of human genetics, vol 99, iss 2 Norman, PJ; Hollenbach, JA; Nemat-Gorgani, N; Marin, WM; Norberg, SJ; Ashouri, E; et al.(2016). Defining KIR and HLA Class I Genotypes at Highest Resolution via High-Throughput Sequencing. AMERICAN JOURNAL OF HUMAN GENETICS, 99(2), 375-391. doi: 10.1016/j.ajhg.2016.06.023. UC San Francisco: Retrieved from: http://www.escholarship.org/uc/item/8fk154vs |
| ISSN: | 0002-9297 1537-6605 |
| DOI: | 10.1016/j.ajhg.2016.06.023 |
| Popis: | The physiological functions of natural killer (NK) cells in human immunity and reproduction depend upon diverse interactions between killer cell immunoglobulin-like receptors (KIRs) and their HLA class I ligands: HLA-A, HLA-B, and HLA-C. The genomic regions containing the KIR and HLA class I genes are unlinked, structurally complex, and highly polymorphic. They are also strongly associated with a wide spectrum of diseases, including infections, autoimmune disorders, cancers, and pregnancy disorders, as well as the efficacy of transplantation and other immunotherapies. To facilitate study of these extraordinary genes, we developed a method that captures, sequences, and analyzes the 13 KIR genes and HLA-A, HLA-B, and HLA-C from genomic DNA. We also devised a bioinformatics pipeline that attributes sequencing reads to specific KIR genes, determines copy number by read depth, and calls high-resolution genotypes for each KIR gene. We validated this method by using DNA from well-characterized cell lines, comparing it to established methods of HLA and KIR genotyping, and determining KIR genotypes from 1000 Genomes sequence data. This identified 116 previously uncharacterized KIR alleles, which were all demonstrated to be authentic by sequencing from source DNA via standard methods. Analysis of just two KIR genes showed that 22% of the 1000 Genomes individuals have a previously uncharacterized allele or a structural variant. The method we describe is suited to the large-scale analyses that are needed for characterizing human populations and defining the precise HLA and KIR factors associated with disease. The methods are applicable to other highly polymorphic genes. |
| Databáze: | OpenAIRE |
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