Assembly and analysis of 100 full MHC haplotypes from the Danish population
- Jacob M. Jensen1,
- Palle Villesen1,2,
- Rune M. Friborg1,
- The Danish Pan-Genome Consortium5,
- Thomas Mailund1,
- Søren Besenbacher1,3 and
- Mikkel H. Schierup1,4
- 1Bioinformatics Research Centre, Aarhus University, 8000 Aarhus C., Denmark;
- 2Department of Clinical Medicine, Aarhus University, 8200 Aarhus N., Denmark;
- 3Department of Molecular Medicine, Aarhus University Hospital, Skejby, 8200 Aarhus N., Denmark;
- 4Department of Bioscience, Aarhus University, 8000 Aarhus C., Denmark
- 6Bioinformatics Centre, Department of Biology, University of Copenhagen, 2200 Copenhagen N, Denmark
- 7Bioinformatics Research Centre, Aarhus University, 8000 Aarhus C, Denmark
- 8iSEQ, Centre for Integrative Sequencing, Aarhus University, 8000 Aarhus C, Denmark
- 9DTU Bioinformatics, Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet, 2800 Kongens Lyngby, Denmark
- 10BGI-Europe, Ole Maaløes Vej 3, 2200 Copenhagen N, Denmark
- 11Department of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark
- 12Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, 2100 Copenhagen Ø, Denmark
- 13Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark
- 14The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, 8000 Aarhus, Denmark
- 15BGI-Shenzhen, Shenzhen 518083, China
- 16School of Bioscience and Biotechnology, South China University of Technology, Guangzhou 510006, China
- 17Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, 2100 Copenhagen Ø, Denmark
- 18Department of Psychology, University of Oslo, 0317 Oslo, Norway
- 19NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, 5021, Norway
- 20Dr. E. Martens Research Group of Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, 5021, Norway
- 21Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden
- 22Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA
- 23Department of Clinical Epidemiology (formerly Institute of Preventive Medicine), Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, 2000 Frederiksberg, Denmark
- 24Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
- 25Department of Cellular and Molecular Medicine, University of Copenhagen, 2200 Copenhagen N, Denmark
- 26Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark
- 27Department of Bioscience, Aarhus University, 8000 Aarhus C, Denmark
Abstract
Genes in the major histocompatibility complex (MHC, also known as HLA) play a critical role in the immune response and variation within the extended 4-Mb region shows association with major risks of many diseases. Yet, deciphering the underlying causes of these associations is difficult because the MHC is the most polymorphic region of the genome with a complex linkage disequilibrium structure. Here, we reconstruct full MHC haplotypes from de novo assembled trios without relying on a reference genome and perform evolutionary analyses. We report 100 full MHC haplotypes and call a large set of structural variants in the regions for future use in imputation with GWAS data. We also present the first complete analysis of the recombination landscape in the entire region and show how balancing selection at classical genes have linked effects on the frequency of variants throughout the region.
Footnotes
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↵5 A full list of Consortium members and their affiliations is available at the end of the text.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.218891.116.
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Freely available online through the Genome Research Open Access option.
- Received November 25, 2016.
- Accepted July 21, 2017.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
