| 1. |
- Baranowska Körberg, Izabella, et al.
(författare)
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A Simple Repeat Polymorphism in the MITF-M Promoter Is a Key Regulator of White Spotting in Dogs
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e104363-
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Tidskriftsartikel (refereegranskat)abstract
- The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia-associated transcription factor) gene. The phenotypic effects of the four S alleles range from solid colour (S) to extreme white spotting (s(w)). We have investigated four candidate mutations associated with the s(w) allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.
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| 2. |
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| 3. |
- Berggren Bremdal, Karin, 1978-
(författare)
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Evolution of MHC Genes and MHC Gene Expression
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 4. |
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| 5. |
- Berggren, Karin T., et al.
(författare)
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Allelic combinations of promoter and exon 2 in DQB1 in dogs and wolves
- 2008
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Ingår i: Journal of Molecular Evolution. - : Springer Science and Business Media LLC. - 0022-2844 .- 1432-1432. ; 67:1, s. 76-84
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Berggren, Karin T, et al.
(författare)
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MHC promoter polymorphism in grey wolves and domestic dogs.
- 2005
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Ingår i: Immunogenetics. - 0093-7711. ; 57:3-4, s. 267-72
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Tidskriftsartikel (refereegranskat)abstract
- A functional immune system requires a tight control over major histocompatibility complex (MHC) gene transcription, as the abnormal MHC expression patterns of severe immunodeficiency and autoimmune diseases demonstrate. Although the regulation of MHC expression has been well documented in humans and mice, little is known in other species. In this study, we detail the level of polymorphism in wolf and dog MHC gene promoters. The promoter regions of the DRB, DQA and DQB locus were sequenced in 90 wolves and 90 dogs. The level of polymorphism was high in the DQB promoters, with variation found within functionally relevant regions, including binding sites for transcription factors. Clear associations between DQB promoters and exon 2 alleles were noted in wolves, indicating strong linkage disequilibrium in this region. Low levels of polymorphism were found within the DRB and DQA promoter regions. However, a variable site was identified within the T box, a TNF-alpha response element, of the DQA promoter. Furthermore, we identified a previously unrecognised 18-base-pair deletion within exon 1 of the DQB locus.
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| 7. |
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| 8. |
- Harder, Robin, et al.
(författare)
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Egestabase – An online evidence platform to discover and explore options to recover plant nutrients from human excreta and domestic wastewater for reuse in agriculture
- 2024
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Ingår i: MethodsX. - : Elsevier B.V.. - 1258-780X .- 2215-0161. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Restoring nutrient circularity across scales is important for ecosystem integrity as well as nutrient and food security. As such, research and development of technologies to recover plant nutrients from various organic residues has intensified. Yet, this emerging field is diverse and difficult to navigate, especially for newcomers. As an increasing number of actors search for circular solutions to nutrient management, there is a need to simplify access to the latest knowledge. Since the majority of nutrients entering urban areas end up in human excreta, we have chosen to focus on human excreta and domestic wastewater. Through systematic mapping with stakeholder engagement, we compiled and consolidated available evidence from research and practice. In this paper, we present ‘Egestabase’ – a carefully curated open-access online evidence platform that presents this evidence base in a systematic and accessible manner. We hope that this online evidence platform helps a variety of actors to navigate evidence on circular nutrient solutions for human excreta and domestic wastewater with ease and keep track of new findings.
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| 9. |
- Macura, Biljana, et al.
(författare)
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Technologies for recovery and reuse of plant nutrients from human excreta and domestic wastewater : a protocol for a systematic map and living evidence platform
- 2021
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Ingår i: Environmental Evidence. - : BioMed Central Ltd. - 2047-2382. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Research and development on the recovery and reuse of nutrients found in human excreta and domestic wastewater has intensified over the past years, continuously producing new knowledge and technologies. However, research impact and knowledge transfer are limited. In particular, uptake and upscaling of new and innovative solutions in practice remain a key challenge. Achieving a more circular use of nutrients thus goes beyond technological innovation and will benefit from a synthesis of existing research being readily available to various stakeholders in the field. The aim of the systematic map and online evidence platform described in this protocol is threefold. First, to collate and summarise scientific research on technologies that facilitate the recovery and reuse of plant nutrients and organic matter found in human excreta and domestic and municipal wastewater. Second, to present this evidence in a way that can be easily navigated by stakeholders. Third, to report on new relevant research evidence to stakeholders as it becomes available. Methods: Firstly, we will produce a baseline systematic map, which will consist of an extension of two previous related syntheses. In a next stage, with help of machine learning and other automation technologies, the baseline systematic map will be transformed into ‘living mode’ that allows for a continually updated evidence platform. The baseline systematic map searches will be performed in 4 bibliographic sources and Google Scholar. All searches will be performed in English. Coding and meta-data extraction will include bibliographic information, locations as well as the recovery and reuse pathways. The living mode will mostly rely on automation technologies in EPPI-Reviewer and the Microsoft Academic database. The new records will be automatically identified and ranked in terms of eligibility. Records above a certain ‘cut-off’ threshold will be manually screened for eligibility. The threshold will be devised based on the empirically informed machine learning model. The evidence from the baseline systematic map and living mode will be embedded in an online evidence platform that in an interactive manner allows stakeholders to visualise and explore the systematic map findings, including knowledge gaps and clusters. © 2021, The Author(s).
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| 10. |
- Seddon, Jennifer, et al.
(författare)
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Evolutionary history of DLA class II haplotypes in canine diabetes mellitus through single nucleotide polymorphism genotyping
- 2010
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Ingår i: Tissue Antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 75:3, s. 218-226
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Tidskriftsartikel (refereegranskat)abstract
- Strong linkage disequilibrium (LD) is a characteristic of the major histocompatibility complex (MHC) region, as well as the genome in general in dogs as a consequence of demographic changes with domestication. Disease association studies of MHC haplotypes may be affected by high LD and the resultant shared genetic backgrounds of haplotypes giving associations with linked but non-causative mutations, and also by convergent haplotypes, in which combinations of alleles have arisen independently. This study provides preliminary tools for dog leukocyte antigen (DLA) class II haplotype analysis with 102 single nucleotide polymorphisms (SNPs) identified in 14.6 kb and genotyping of 20 of these SNPs to tag haplotypes in 60 dogs with diabetes mellitus and in 49 non-diabetic dogs. The pattern of LD and analysis of SNP patterns indicated combinations of exon 2 alleles have arisen through both recombination and convergence. For exon 2 haplotypes associated with susceptibility or protection from diabetes mellitus, a region of fixed differences in SNPs across the DQ region was observed, suggesting a region outside exon 2 may be implicated in disease association. Four new DQB1 promoter alleles restricted to diabetic dogs were identified, as well as a substitution difference in the X1 box of the DQB1 promoter that will potentially modify the effect of the protective haplotypes within diabetic dogs
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