University of Oulu

Niskanen, A.K., Kennedy, L.J., Lohi, H. et al. No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci. Canine Genet Epidemiol 3, 9 (2016).

No evidence of prenatal diversifying selection at locus or supertype levels in the dog MHC class II loci

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Author: Niskanen, Alina K.1,2; Kennedy, Lorna J.3; Lohi, Hannes4,5;
Organizations: 1Department of Genetics and Physiology, University of Oulu
2Present address: Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology
3Centre for Integrated Genomic Medical Research, University of Manchester
4Department of Veterinary Biosciences, Research Programs Unit, Molecular Neurology, University of Helsinki
5Folkhälsan Institute of Genetics, Biomedicum Helsinki
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.8 MB)
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Language: English
Published: Springer Nature, 2016
Publish Date: 2016-12-15


Background: Despite decades of studying, the mechanisms maintaining high diversity in the genes of the Major Histocompatibility Complex (MHC) are still puzzling scientists. In addition to pathogen recognition and other functions, MHC molecules may act prenatally in mate choice and in maternal-foetal interactions. These interactions are potential selective mechanisms that increase genetic diversity in the MHC. During pregnancy, immune response has a dual role: the foetus represents foreign tissue compared to mother, but histo-incompatibility is required for successful pregnancy. We have studied the prenatal selection in MHC class II loci (DLA-DQA1, DLA-DQB1 and DLA-DRB1) in domestic dogs by comparing the observed and expected offspring genotype proportions in 110 dog families. Several potential selection targets were addressed, including the peptide-binding site, the MHC locus, three-locus haplotype and supertype levels. For the supertype analysis, the first canine supertype classification was created based on in silico analysis of peptide-binding amino-acid polymorphism.

Results: In most loci and levels, no deviation from the expected genotype frequencies was observed. However, one peptide-binding site in DLA-DRB1 had an excess of heterozygotes among the offspring. In addition, if the father shared a DLA-DRB1 allele with the mother, that allele was inherited by the offspring more frequently than expected, suggesting the selective advantage of a histo-compatible foetus, in contrast to our expectations.

Conclusions: We conclude that there is some evidence of post-copulatory selection at nucleotide site level in the MHC loci of pet dogs. But due to no indication of selection at locus, three-locus, or supertype levels, we estimated that the prenatal selection coefficient is less than 0.3 in domestic dogs and very likely other factors are more important in maintaining the genetic diversity in MHC loci.

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Series: Canine genetics and epidemiology
ISSN: 2052-6687
ISSN-E: 2052-6687
ISSN-L: 2052-6687
Volume: 3
Article number: 9 (2016)
DOI: 10.1186/s40575-016-0038-9
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
Copyright information: © Niskanen et al. 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.