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J Immunol. 2018 Mar 1;200(5):1692-1701. doi: 10.4049/jimmunol.1701480. Epub 2018 Jan 22.

Human and Rhesus Macaque KIR Haplotypes Defined by Their Transcriptomes.

Author information

1
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands.
2
Department of Immunogenetics, Sanquin, 1066 CX Amsterdam, the Netherlands.
3
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; and.
4
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, the Netherlands; bontrop@bprc.nl.
5
Department of Theoretical Biology and Bioinformatics, Utrecht University, 3584 CH Utrecht, the Netherlands.

Abstract

The killer-cell Ig-like receptors (KIRs) play a central role in the immune recognition in infection, pregnancy, and transplantation through their interactions with MHC class I molecules. KIR genes display abundant copy number variation as well as high levels of polymorphism. As a result, it is challenging to characterize this structurally dynamic region. KIR haplotypes have been analyzed in different species using conventional characterization methods, such as Sanger sequencing and Roche/454 pyrosequencing. However, these methods are time-consuming and often failed to define complete haplotypes, or do not reach allele-level resolution. In addition, most analyses were performed on genomic DNA, and thus were lacking substantial information about transcription and its corresponding modifications. In this paper, we present a single-molecule real-time sequencing approach, using Pacific Biosciences Sequel platform to characterize the KIR transcriptomes in human and rhesus macaque (Macaca mulatta) families. This high-resolution approach allowed the identification of novel Mamu-KIR alleles, the extension of reported allele sequences, and the determination of human and macaque KIR haplotypes. In addition, multiple recombinant KIR genes were discovered, all located on contracted haplotypes, which were likely the result of chromosomal rearrangements. The relatively high number of contracted haplotypes discovered might be indicative of selection on small KIR repertoires and/or novel fusion gene products. This next-generation method provides an improved high-resolution characterization of the KIR cluster in humans and macaques, which eventually may aid in a better understanding and interpretation of KIR allele-associated diseases, as well as the immune response in transplantation and reproduction.

PMID:
29358278
DOI:
10.4049/jimmunol.1701480
[Indexed for MEDLINE]
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