| 1. |
- Wilbe, Maria, et al.
(författare)
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DLA Class II Alleles Are Associated with Risk for Canine Symmetrical Lupoid Onychodystropy (SLO)
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:8, s. e12332-
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Tidskriftsartikel (refereegranskat)abstract
- Symmetrical lupoid onychodystrophy (SLO) is an immune-mediated disease in dogs affecting the claws with a suggested autoimmune aethiology. Sequence-based genotyping of the polymorphic exon 2 from DLA-DRB1, -DQA1, and -DQB1 class II loci were performed in a total of 98 SLO Gordon setter cases and 98 healthy controls. A risk haplotype (DRB1*01801/DQA1*00101/DQB1*00802) was present in 53% of cases and 34% of controls and conferred an elevated risk of developing SLO with an odds ratio (OR) of 2.1. When dogs homozygous for the risk haplotype were compared to all dogs not carrying the haplotype the OR was 5.4. However, a stronger protective haplotype (DRB1*02001/DQA1*00401/DQB1*01303, OR = 0.03, 1/OR = 33) was present in 16.8% of controls, but only in a single case (0.5%). The effect of the protective haplotype was clearly stronger than the risk haplotype, since 11.2% of the controls were heterozygous for the risk and protective haplotypes, whereas this combination was absent from cases. When the dogs with the protective haplotype were excluded, an OR of 2.5 was obtained when dogs homozygous for the risk haplotype were compared to those heterozygous for the risk haplotype, suggesting a co-dominant effect of the risk haplotype. In smaller sample sizes of the bearded collie and giant schnauzer breeds we found the same or similar haplotypes, sharing the same DQA1 allele, over-represented among the cases suggesting that the risk is associated primarily with DLA-DQ. We obtained conclusive results that DLA class II is significantly associated with risk of developing SLO in Gordon setters, thus supporting that SLO is an immune-mediated disease. Further studies of SLO in dogs may provide important insight into immune privilege of the nail apparatus and also knowledge about a number of inflammatory disorders of the nail apparatus like lichen planus, psoriasis, alopecia areata and onycholysis.
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| 2. |
- Yusnizar, Yulnawati, et al.
(författare)
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Microphthalmia-associated transcription factor mutations are associated with white-spotted coat color in swamp buffalo
- 2015
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Ingår i: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 46:6, s. 676-682
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Tidskriftsartikel (refereegranskat)abstract
- A candidate gene analysis of the microphthalmia-associated transcription factor (MITF) gene was used in an attempt to identify the genetic basis for a white-spotted coat color phenotype in the Asian swamp buffalo (Bubalus bubalis carabanensis). Ninety-three buffaloes32 solid, 38 spotted and 23 white individualswere Sanger-sequenced for all MITF exons as well as highly conserved intronic and flanking regions. MITFcDNA representing skin and iris tissue from six spotted, nine solid and one white buffaloes was also Sanger-sequenced to confirm detected mutations. Two independent loss-of-function mutations, a premature stop codon (c.328C>T, p.Arg110*) and a donor splice-site mutation (c.840+2T>A, p.Glu281_Leu282Ins8), both of which cause white-spotted coat color in swamp buffaloes, were identified. The nonsense mutation leads to a premature stop codon in exon 3, and likely removal of the resulting mRNA via nonsense-mediated decay pathway, whereas the donor splice-site mutation leads to aberrant splicing of exon 8 that encodes part of a highly conserved region of MITF. The resulting insertion of eight amino acid residues is expected to perturb the leucine zipper part in the basic helix-loop-helix leucine zipper (bHLH-Zip) domain and will most likely influence dimerization and DNA binding capacity. Electrophoretic mobility shift assay was performed using mutant and wild-type MITF proteins and showed that the mutant MITF protein resulting from the splice-site mutation decreased invitro DNA binding capacity compared to wild-type MITF. White-spotted buffalo bulls are sacrificed in funeral ceremonies in Tana Toraja, Indonesia, because they are considered holy, and our results show that genetic variation causes a tie to the cultural use of these buffaloes.
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| 3. |
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| 4. |
- Ahlgren, Kerstin, M., et al.
(författare)
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Type I Interferon signature in Nova Scotia duck tolling retriever dogs with steroid responsive meningitis-arteritis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are prone to develop a disease complex in some aspects resembling human systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells (PBMCs) from human SLE patients have an increased mRNA expression type I interferon (IFN) regulated genes. However, it is unknown whether diseased dogs also display the typical type I IFN signature. Methods: To test canine sera for their capacity to induce type I IFN response Mardin-Darby canine kidney (MDCK) cells were cultured with sera from healthy dogs (n=25), immune-mediated rheumatic disease (IMRD) dogs with anti-nuclear antibodies (ANA+) (n=30) or dogs with steroid responsive meningitis-arteritis (SRMA) (n=25). mRNA expression of the genes MX1, IFIT1 and CXCL10 was measured by quantitative Real Time PCR. Results: A highly significant (p=0.0009) increase in mRNA expression of the type I IFN responsive gene MX1 was detected in cells stimulated by sera from dogs with SRMA, but not from IMRD ANA+ dogs. Expression of IFIT1 was twice as high in cells stimulated by sera from dogs with SRMA compared to both healthy dogs and ANA+ dogs. The mean expression of CXCL10 was nearly ten times higher in cells stimulated by sera from SRMA dogs than by ANA+ dogs and four times higher compared to cells stimulated by control dogs. Conclusion: Presence of type I IFN in sera from diseased NSDTR dogs was found in this study. This implies that this canine model can be used for identification of pathways of importance for autoimmune disorders in humans and for testing of novel therapeutic approaches. Our results can also be a step on the way towards personalized drugs in these dogs.
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| 5. |
- Barrdahl, Maria, et al.
(författare)
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Tågresenärens upplevelse av landskapet : en studie av järnvägssträckan Höör-Osby
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Vägar och järnvägar har en väsentlig betydelse för människors tillgänglighet och möjlighet att uppleva landskap. Dagligen färdas tusentals människor med tåg och upplever landskap på ett eller annat sätt när de färdas från en plats till en annan. Resenären blir en betraktare av det yttre landskapet och landskapet utanför blir en bild, en scen i rörelse. Beroende på hastighet är bilden tydligare, mer detaljrik eller ibland snabbt och flyktigt förbi. Med hjälp av digitala analyser i GIS (Geografiska informationssystem), identifieras natur- och kulturvärden längs med järnvägen. De digitala analyserna ger ett underlag för en diskussion kring den utvecklingspotential som finns för landskapet kring järnvägen och hur man med skötselåtgärder, kan skapa en mer tilltalande landskapsbild för tågresenären. Detta är en tänkbar arbetsmetod och ett undersökande för hur man kan arbeta med insatser kring skötselgatan för att medvetet lyfta fram värdefulla utblickar, byggnader, landskapsvyer, landmärken etc. för att ge tågresenären en vackrare och mer upplevelserik tågresa.
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| 6. |
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| 7. |
- Farias, Fabiana H. G., et al.
(författare)
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A rare regulatory variant in the MEF2D gene affects gene regulation and splicing and is associated with a SLE sub-phenotype in Swedish cohorts
- 2019
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 27, s. 432-441
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disorder with heterogeneous clinical presentation and complex etiology involving the interplay between genetic, epigenetic, environmental and hormonal factors. Many common SNPs identified by genome wide-association studies (GWAS) explain only a small part of the disease heritability suggesting the contribution from rare genetic variants, undetectable in GWAS, and complex epistatic interactions. Using targeted re-sequencing of coding and conserved regulatory regions within and around 215 candidate genes selected on the basis of their known role in autoimmunity and genes associated with canine immune-mediated diseases, we identified a rare regulatory variant rs200395694:G > T located in intron 4 of the MEF2D gene encoding the myocyte-specific enhancer factor 2D transcription factor and associated with SLE in Swedish cohorts (504 SLE patients and 839 healthy controls, p = 0.014, CI = 1.1-10). Fisher's exact test revealed an association between the genetic variant and a triad of disease manifestations including Raynaud, anti-U1-ribonucleoprotein (anti-RNP), and anti-Smith (anti-Sm) antibodies (p = 0.00037) among the patients. The DNA-binding activity of the allele was further studied by EMSA, reporter assays, and minigenes. The region has properties of an active cell-specific enhancer, differentially affected by the alleles of rs200395694:G > T. In addition, the risk allele exerts an inhibitory effect on the splicing of the alternative tissue-specific isoform, and thus may modify the target gene set regulated by this isoform. These findings emphasize the potential of dissecting traits of complex diseases and correlating them with rare risk alleles with strong biological effects.
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| 8. |
- Fegraeus, Kim, et al.
(författare)
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An endothelial regulatory module links blood pressure regulation with elite athletic performance
- 2024
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 20:6
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Tidskriftsartikel (refereegranskat)abstract
- The control of transcription is crucial for homeostasis in mammals. A previous selective sweep analysis of horse racing performance revealed a 19.6 kb candidate regulatory region 50 kb downstream of the Endothelin3 (EDN3) gene. Here, the region was narrowed to a 5.5 kb span of 14 SNVs, with elite and sub-elite haplotypes analyzed for association to racing performance, blood pressure and plasma levels of EDN3 in Coldblooded trotters and Standardbreds. Comparative analysis of human HiCap data identified the span as an enhancer cluster active in endothelial cells, interacting with genes relevant to blood pressure regulation. Coldblooded trotters with the sub-elite haplotype had significantly higher blood pressure compared to horses with the elite performing haplotype during exercise. Alleles within the elite haplotype were part of the standing variation in pre-domestication horses, and have risen in frequency during the era of breed development and selection. These results advance our understanding of the molecular genetics of athletic performance and vascular traits in both horses and humans.
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| 9. |
- Halling Linder, Cecilia, et al.
(författare)
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Bone Alkaline Phosphatase and Tartrate-Resistant Acid Phosphatase: Potential Co-regulators of Bone Mineralization
- 2017
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Ingår i: Calcified Tissue International. - : SPRINGER. - 0171-967X .- 1432-0827. ; 101:1, s. 92-101
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylated osteopontin (OPN) inhibits hydroxyapatite crystal formation and growth, and bone alkaline phosphatase (BALP) promotes extracellular mineralization via the release of inorganic phosphate from the mineralization inhibitor inorganic pyrophosphate (PPi). Tartrate-resistant acid phosphatase (TRAP), produced by osteoclasts, osteoblasts, and osteocytes, exhibits potent phosphatase activity towards OPN; however, its potential capacity as a regulator of mineralization has not previously been addressed. We compared the efficiency of BALP and TRAP towards the endogenous substrates for BALP, i.e., PPi and pyridoxal 5-phosphate (PLP), and their impact on mineralization in vitro via dephosphorylation of bovine milk OPN. TRAP showed higher phosphatase activity towards phosphorylated OPN and PPi compared to BALP, whereas the activity of TRAP and BALP towards PLP was comparable. Bovine milk OPN could be completely dephosphorylated by TRAP, liberating all its 28 phosphates, whereas BALP dephosphorylated at most 10 phosphates. OPN, dephosphorylated by either BALP or TRAP, showed a partially or completely attenuated phosphorylation-dependent inhibitory capacity, respectively, compared to native OPN on the formation of mineralized nodules. Thus, there are phosphorylations in OPN important for inhibition of mineralization that are removed by TRAP but not by BALP. In conclusion, our data indicate that both BALP and TRAP can alleviate the inhibitory effect of OPN on mineralization, suggesting a potential role for TRAP in skeletal mineralization. Further studies are warranted to explore the possible physiological relevance of TRAP in bone mineralization.
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| 10. |
- Hamlin, Helene, et al.
(författare)
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Immunmedierade sjukdomar hos hund
- 2012
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Ingår i: Svensk Veterinärtidning. - 0346-2250. ; 64, s. 37-40
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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