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Allelic combinations of promoter and exon 2 in DQB1 in dogs and wolves
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
2008 (English)In: Journal of Molecular Evolution, ISSN 0022-2844, Vol. 67, no 1, 76-84 p.Article in journal (Refereed) Published
Abstract [en]

Polymorphism of PBRs of the major histocompatibility complex (MHC) genes is well recognized, but the polymorphism also extends to proximal promoter regions. Examining DQB1 variability in dogs and wolves, we identified 7 promoter variants and 13 exon 2 alleles among 89 dogs, including a previously unknown DQB1 exon 2 allele, and 8 promoter variants and 9 exon 2 alleles among 85 wolves. As expected from previous studies and from a close chromosomal location, strong linkage disequilibrium was demonstrated in both wolves and dogs by having significantly fewer promoter/exon 2 combinations than expected from simulations of randomized data sets. Interestingly, we noticed weaker haplotypic associations in dogs than in wolves. Dogs had twice as many promoter/exon 2 combinations as wolves and an almost 2-fold difference in the number of exon 2 alleles per promoter variant. This difference was not caused by an admixture of breeds in our group of dogs because the high ratio of observed to expected number of haplotypes persisted within a single dog breed, the German Shepherd. Ewens-Watterson tests indicated that both the promoter and exon 2 are under the balancing selection, and both regions appear to be more recently derived in the dog than in the wolf. Hence, although reasons for the differences are unknown, they may relate to altered selection pressure on patterns of expression. Deviations from normal MHC expression patterns have been associated with autoimmune diseases, which occur frequently in several dog breeds. Further knowledge about these deviations may help us understand the source of such diseases.

Place, publisher, year, edition, pages
2008. Vol. 67, no 1, 76-84 p.
Keyword [en]
dog, DLA, DQB1, MHC, promoter, linkage disequilibrium, wolf
National Category
Biological Sciences
URN: urn:nbn:se:uu:diva-109175DOI: 10.1007/s00239-008-9126-0ISI: 000258088000008OAI: oai:DiVA.org:uu-109175DiVA: diva2:249059
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2010-04-07Bibliographically approved
In thesis
1. Evolution of MHC Genes and MHC Gene Expression
Open this publication in new window or tab >>Evolution of MHC Genes and MHC Gene Expression
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Polymorphism in coding regions and regions controlling gene expression is the major determinant of adaptive differences in natural populations. Genes of the major histocompatibility complex (MHC) possess a high level of genetic variation, which is maintained by selection over long coalescence times. MHC genes encode antigen-presenting molecules in the adaptive immune system, which protects the host from infectious diseases. However, MHC molecules may also present self-peptides and for most autoimmune diseases there is a genetic factor associated with the MHC.

MHC genes have been used to learn about the interplay of selection and historical population events. In domestic dogs and their progenitor, the wolf, I explored factors associated with domestication and breed formation and their influence not only on MHC coding regions but also on the haplotypic structure of the class II region. Polymorphism and strong selection was demonstrated in the proximal promoters of MHC genes in dogs and wolves. Hence, genetic variation associated with MHC gene expression may have at least equal importance for a well functioning immune system. Associations between promoter sequences and particular coding alleles suggested allele-specific expression patterns. SNP haplotypes of the MHC class II region revealed ancestral as well as convergent haplotypes, in which combinations of alleles are kept by selection. Interestingly, weaker allelic associations were found between different genes and between coding regions and promoters in dogs compared to wolves. Potentially, this could cause insufficient defense against infections and predispose dogs to autoimmune diseases. For example, I identified a site in the promoter region that showed a consistent difference between haplotypes conferring susceptibility and protection to diabetes in dogs, which should be investigated further.

Furthermore, I investigated how selection and demographic changes associated with glacial and inter-glacial periods have affected MHC variation in European hedgehogs and extended the prevailing knowledge concerning their population history.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 69 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 736
major histocompatibilty complex, dog leukocyte antigen, balancing selection, linkage disequilibrium, promoter, diabetes mellitus, Canis familiaris, Canis lupus, Erinaceus europaeus, Erinaceus concolor
National Category
Research subject
Biology with specialization in Evolutionary Genetics
urn:nbn:se:uu:diva-122011 (URN)978-91-554-7792-9 (ISBN)
Public defence
2010-05-21, Evolutionsbiologiskt centrum, Zootissalen, Villavägen 9, Uppsala, 09:00 (English)
Available from: 2010-04-29 Created: 2010-04-05 Last updated: 2010-04-29Bibliographically approved

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