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  Construction and benchmarking of a multi-ethnic reference panel for the imputation of HLA class I and II alleles

Degenhardt, F., Wendorff, M., Wittig, M., Ellinghaus, E., Datta, L. W., Schembri, J., et al. (2018). Construction and benchmarking of a multi-ethnic reference panel for the imputation of HLA class I and II alleles. Human Molecular Genetics, 00(00): ddy443. doi:10.1093/hmg/ddy443.

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Datensatz-Permalink: http://hdl.handle.net/21.11116/0000-0002-C8D7-A Versions-Permalink: http://hdl.handle.net/21.11116/0000-0002-CA65-9
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 Urheber:
Degenhardt, Frauke, Autor
Wendorff, Mareike, Autor
Wittig, Michael, Autor
Ellinghaus, Eva, Autor
Datta, Lisa W., Autor
Schembri, John, Autor
Ng, Siew C., Autor
Rosati, Elisa, Autor
Hübenthal, Matthias, Autor
Ellinghaus, David, Autor
Jung, Eun S., Autor
Lieb, Wolfgang, Autor
Abedian, Shifteh, Autor
Malekzadeh, Reza, Autor
Cheon, Jae H., Autor
Ellul, Pierre, Autor
Sood, Ajit, Autor
Midha, Vandana, Autor
Bk, Thelma, Autor
Wong, Sunny H., Autor
Schreiber, Stefan, AutorYamazaki, Keiko, AutorKubo, Michiaki, AutorBoucher, Gabrielle, AutorRioux, John, AutorLenz, Tobias L.1, Autor              Brant, Steven R., AutorFranke, Andre, Autor mehr..
Affiliations:
1Emmy Noether Research Group Evolutionary Immunogenomics, Department Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2068286              

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 Zusammenfassung: Genotype imputation of the human leukocyte antigen (HLA) region is a cost-effective means to infer classical HLA alleles from inexpensive and dense SNP array data. In the research setting, imputation helps avoid costs for wet lab-based HLA typing and thus renders association analyses of the HLA in large cohorts feasible. Yet, most HLA imputation reference panels target Caucasian ethnicities and multi-ethnic panels are scarce. We compiled a high-quality multi-ethnic reference panel based on genotypes measured with lllumina’s Immunochip genotyping array and HLA types established using a high-resolution next generation sequencing approach. Our reference panel includes more than 1,300 samples from Germany, Malta, China, India, Iran, Japan and Korea and samples of African American ancestry for all classical HLA class I and II alleles including HLA-DRB3/4/5. Applying extensive cross-validation, we benchmarked the imputation using the HLA imputation tool HIBAG, our multi-ethnic reference and an independent, previously published data set compiled of subpopulations of the 1000 Genomes project. We achieved average imputation accuracies higher than 0.924 for the commonly studied HLA-A, -B, -C, -DQB1 and -DRB1 genes across all ethnicities. We investigated allele-specific imputation challenges in regard to geographic origin of the samples using sensitivity and specificity measurements as well as allele frequencies and identified HLA alleles that are challenging to impute for each of the populations separately. In conclusion, our new multi-ethnic reference data set allows for high resolution HLA imputation of genotypes at all classical HLA class I and II genes including the HLA-DRB3/4/5 loci based on diverse ancestry populations.

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Sprache(n): eng - Englisch
 Datum: 2018-12-262018
 Publikationsstatus: Im Druck veröffentlicht
 Seiten: -
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: DOI: 10.1093/hmg/ddy443
BibTex Citekey: doi:10.1093/hmg/ddy443
 Art des Abschluß: -

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Titel: Human Molecular Genetics
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: Oxford, England : IRL Press
Seiten: 52 Band / Heft: 00 (00) Artikelnummer: ddy443 Start- / Endseite: - Identifikator: ISSN: 0964-6906
CoNE: https://pure.mpg.de/cone/journals/resource/954925581153