| 1. |
- Mathioudaki, Argyri, Ph.D student, 1986-, et al.
(författare)
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The sex-stratified genetic architecture of ankylosing spondylitis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sexual dimorphism is an emerging feature of ankylosing spondylitis (AS), a chronic rheumatic condition affecting upto three times more men than women. Using 691 individuals from a Swedish case-control cohort, we revealed thatsex biases are also a hallmark of AS genetic predisposition, and that this multifactorial disease is in part driven byboth rare and common variants. We identified SNPs via the targeted re-sequencing of 7 270 coding and non-codingloci, and assessed novel patterns of association with both single marker and aggregate loci SKAT tests. The malespecific RUNX3 locus (including rs7414934, OR=2.58, p=1.7x10-5) and female specific MICB SKAT locus (27variants, p=1.2x10-6; rs3828903, OR=4.62, p=6.2x10-13) exceeded discovery thresholds. Multiple risk variants fromeach locus were shown to be functionally active in immune (Jurkat), skin (HaCat) and bone (SaOS-2) cell lines.Differential patterns of genetic predisposition may point to alternative disease mechanisms in male and femalepatients. Genetic and functional analyses demonstrated that risk alleles should not be considered in isolation and thatassociated variants would likely affect gene regulation across multiple tissues. This work illustrates the need toconsider the contribution of sex to the genetics of AS and the duality that individual loci may play in the key clinical outcomes of disease.
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| 2. |
- Artman, Henrik, 1968-, et al.
(författare)
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Effektiv miljötillsyn : slutrapport
- 2013
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Målsättningen har varit att ta fram ny kunskap inom miljötillsynen och därigenom uppnå en effektivare miljötillsyn samt att få in nya vetenskapliga perspektiv på miljötillsyn.I rapporten studeras metoder för inspektioner och det kommunikativa samspelet mellan inspektören och företrädare för den verksamhet som inspekteras, hur den institutionella ramen för inspektionsprocessen fungerar samt visar på möjligheter att mäta effekterna av inspektioner och tillsyn.Naturvårdsverket kommer att ha resultatet som ett kunskapsunderlag i fortsatt arbete med tillsynsvägledning och utveckling av hur tillsyn och tillsynsvägledning kan följas upp och utvärderas.
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| 3. |
- Axelsson, Erik, et al.
(författare)
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The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels
- 2021
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:9
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Tidskriftsartikel (refereegranskat)abstract
- Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.
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| 4. |
- Bianchi, Matteo, et al.
(författare)
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Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs
- 2020
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Ingår i: BMC Genomics. - : BMC. - 1471-2164. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed.Results: By employing genome-wide association followed by fine-mapping (top variant p-value=5.7x10(-6)), integrated with whole-genome resequencing and copy number variation analysis, we detected a similar to 8.9 kbp deletion strongly associated (p-value=0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail.Conclusions: Our results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.
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| 5. |
- Boschini, Anne, et al.
(författare)
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Gender and altruism in a random sample
- 2018
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Ingår i: Journal of Behavioral and Experimental Economics. - : Elsevier BV. - 2214-8043 .- 2214-8051. ; 77, s. 72-77
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Tidskriftsartikel (refereegranskat)abstract
- We study gender differences in altruism in a large random sample of the Swedish population using a standard dictator game. Beside a baseline treatment we implement a priming treatment where participants are reminded of their gender, and two treatments with known male and female counterpart respectively. We find suggestive evidence that women are more altruistic than men only in the priming treatment. A post-hoc analysis using data on interviewer gender to explore gender context effects indicates that priming affects behavior only in mixedgender contexts.
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| 6. |
- Boschini, Anne, et al.
(författare)
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Gender, risk preference and willingness to compete in a random sample of the Swedish population
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Working paper.Experimental results from student or other non-representative convenience samples often suggest that men, on average, are more risk-taking and competitive than women. Here we explore whether these gender preference gaps also exist in a simple random sample of the Swedish adult population. Our design comprises four different treatments to systematically explore how the experimental context may impact gender gaps; a baseline treatment, a treatment where participants are primed with their own gender, and a treatment where the participants know the gender of their counterpart (man or woman). We look at willingness to compete in two domains: a math task and a verbal task. We find no gender differences in risk preferences or in willingness to compete in the verbal task in this random sample. There is some support for men being more competitive than women in the math task, in particular in the pooled sample. The effect size is however considerably smaller than what is typically found. We further find no consistent impact of treatment on (the absence of) the gender gap in preferences.
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| 7. |
- Boschini, Anne, et al.
(författare)
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Gender, risk preferences and willingness to compete in a random sample of the Swedish population
- 2018
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Experimental results from student or other non-representative convenience samples often suggest that men, on average, are more risk-taking and competitive than women. Here we explore whether these gender preference gaps also exist in a simple random sample of the Swedish adult population. Our design comprises four different treatments to systematically explore how the experimental context may impact gender gaps; a baseline treatment, a treatment where participants are primed with their own gender, and a treatment where the participants know the gender of their counterpart (man or woman). We look at willingness to compete in two domains: a math task and a verbal task. We find no gender differences in risk preferences or in willingness to compete in the verbal task in this random sample. There is some support for men being more competitive than women in the math task, in particular in the pooled sample. The effect size is however considerably smaller than what is typically found. We further find no consistent impact of treatment on (the absence of) the gender gap in preferences.
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| 8. |
- Boschini, Anne, et al.
(författare)
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Gender, risk preferences and willingness to compete in a random sample of the Swedish population
- 2019
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Ingår i: Journal of Behavioral and Experimental Economics. - : Elsevier BV. - 2214-8043 .- 2214-8051. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- Experimental results from student and other non-representative convenience samples often suggest that men, on average, are more risk taking and competitive than women. We explore whether these gender preference gaps also exist in incentivized tasks in a simple random sample of the Swedish adult population. Our design comprises four different conditions to systematically explore how the experimental context may impact gender gaps; a baseline condition, a condition where participants are primed with their own gender, and two conditions where the participants know the gender of their counterpart (man or woman). We further look at competitiveness in two domains: a math task and a verbal task. We find no gender gap in risk taking or competitiveness in the verbal task in this random sample. There is some support for men being more competitive than women in the math task in the pooled sample, but the effect size is small. We further find no consistent impact of the respective conditions on (the absence of) the gender gap in preferences.
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| 9. |
- Carlsson, Mattias, et al.
(författare)
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A Ham1p-Dependent Mechanism and Modulation of the Pyrimidine Biosynthetic Pathway can both Confer Resistance to 5-Fluorouracil in Yeast
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10, s. e52094-
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Tidskriftsartikel (refereegranskat)abstract
- 5-Fluorouracil (5-FU) is an anticancer drug and pyrimidine analogue. A problem in 5-FU therapy is acquired resistance to the drug. To find out more about the mechanisms of resistance, we screened a plasmid library in yeast for genes that confer 5-FU resistance when overexpressed. We cloned five genes: CPA1, CPA2, HMS1, YAE1 and YJL055W. CPA1 and CPA2 encode a carbamoyl phosphate synthase involved in arginine biosynthesis and HMS1 a helix-loop-helix transcription factor. Our results suggest that CPA1, CPA2, and HMS1 confer 5-FU resistance by stimulating pyrimidine biosynthesis. Thus, they are unable to confer 5-FU resistance in a ura2 mutant, and inhibit the uptake and incorporation into RNA of both uracil and 5-FU. In contrast, YAE1 and YJL055W confer 5-FU resistance in a ura2 mutant, and selectively inhibit incorporation into RNA of 5-FU but not uracil. YAE1 is the strongest resistance gene, but it partially depends on YJL055W for its function. This suggests that YAE1 and YJL055W function together in a novel mechanism for detoxification of 5-FU and other pyrimidine analogs. Yae1p belongs to a small protein family with only two members, which are conserved in all eukaryotes examined. One of the human homologs, TAOS1, is overexpressed in oral carcinomas.
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| 10. |
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