Unravelling the architecture of major histocompatibility complex class II haplotypes in rhesus macaques
- Nanine de Groot1,
- Marit van der Wiel1,
- Ngoc Giang Le1,
- Natasja G. de Groot1,
- Jesse Bruijnesteijn1,3 and
- Ronald E. Bontrop1,2,3
- 1Department of Comparative Genetics and Refinement, BPRC, 2288 GJ Rijswijk, the Netherlands;
- 2Department of Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands
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↵3 These authors share last authorship.
Abstract
The regions in the genome that encode components of the immune system are often featured by polymorphism, copy number variation, and segmental duplications. There is a need to thoroughly characterize these complex regions to gain insight into the impact of genomic diversity on health and disease. Here we resolve the organization of complete major histocompatibility complex (MHC) class II regions in rhesus macaques by using a long-read sequencing strategy (Oxford Nanopore Technologies) in concert with adaptive sampling. In particular, the expansion and contraction of the primate DRB-region appear to be a dynamic process that involves the rearrangement of different cassettes of paralogous genes. These chromosomal recombination events are propagated by a conserved pseudogene, DRB6, which features the integration of two retroviral elements. In contrast, the DRA locus appears to be protected from rearrangements, which may be owing to the presence of an adjacently located truncated gene segment, DRB9. With our sequencing strategy, the annotation, evolutionary conservation, and potential function of pseudogenes can be reassessed, an aspect that was neglected by most genome studies in primates. Furthermore, our approach facilitates the characterization and refinement of an animal model essential to study human biology and disease.
Footnotes
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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 https://www.genome.org/cgi/doi/10.1101/gr.278968.124.
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Freely available online through the Genome Research Open Access option.
- Received January 22, 2024.
- Accepted May 28, 2024.
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/.
