| 1. |
- Arendt, Maja Louise, et al.
(författare)
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Genome-Wide Association Study of Golden Retrievers Identifies Germ-Line Risk Factors Predisposing to Mast Cell Tumours
- 2015
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Canine mast cell tumours (CMCT) are one of the most common skin tumours in dogs with a major impact on canine health. Certain breeds have a higher risk of developing mast cell tumours, suggesting that underlying predisposing germ-line genetic factors play a role in the development of this disease. The genetic risk factors are largely unknown, although somatic mutations in the oncogene C-KIT have been detected in a proportion of CMCT, making CMCT a comparative model for mastocytosis in humans where C-KIT mutations are frequent. We have performed a genome wide association study in golden retrievers from two continents and identified separate regions in the genome associated with risk of CMCT in the two populations. Sequence capture of associated regions and subsequent fine mapping in a larger cohort of dogs identified a SNP associated with development of CMCT in the GNAI2 gene (p = 2.2x10(-16)), introducing an alternative splice form of this gene resulting in a truncated protein. In addition, disease associated haplotypes harbouring the hyaluronidase genes HYAL1, HYAL2 and HYAL3 on cfa20 and HYAL4, SPAM1 and HYALP1 on cfa14 were identified as separate risk factors in European and US golden retrievers, respectively, suggesting that turnover of hyaluronan plays an important role in the development of CMCT.
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| 2. |
- Biasoli, Deborah, et al.
(författare)
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A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers
- 2019
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Ingår i: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. Author summary The combination of various genetic and environmental risk factors makes the understanding of the molecular circuitry behind complex diseases, like cancer, a major challenge. The homogeneous nature of pedigree dog breed genomes makes these dogs ideal for the identification of both simple disease-causing genetic variants and genetic risk factors for complex diseases. Mast cell tumours are the most common type of canine skin cancer, and one of the most common cancers affecting dogs of most breeds. Several breeds, including Labrador Retrievers (which represent one of the most popular dog breeds), have an elevated risk of mast cell tumour development. Here, by using a methodological approach that combined different techniques, we identified a common inherited synonymous variant, that predisposes Labrador Retrievers to mast cell tumour development. Interestingly, we showed that this variant, despite its synonymous nature, appears to have an effect on translation dynamics as it is associated with reduced levels of DSCAM, a cell adhesion molecule. The results presented here reveal dysregulation of cell adhesion to be an important factor in mast cell tumour pathogenesis, and also highlight the important role that synonymous variants can play in complex diseases.
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| 3. |
- Hugelius, Karin, 1977-, et al.
(författare)
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The Power of Radio to Promote Health and Resilience in Natural Disasters : A Review
- 2019
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 16:14
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Forskningsöversikt (refereegranskat)abstract
- Humanitarian radio has been used in humanitarian aid efforts and after natural disasters over the last 15 years. However, the effects have barely been evaluated, and there are few scientific reports on the impact of radio as a disaster health response intervention. Therefore, this study aimed to provide an overview of the use and impact of humanitarian radio in natural disasters from a health perspective. A literature review of 13 scientific papers and grey literature resources was conducted. The results show that humanitarian radio could be used to promote both physical and psychosocial wellbeing by providing health-related information, advice and psychosocial support in natural disasters. Community resilience can be enhanced by the promotion of community engagement and can strengthen self-efficacy and community efficacy. Radio also has the potential to cost-effectively reach a large number of affected people in areas with severely damaged infrastructure. Radio could, therefore, contribute to health recovery and wellbeing from both individual and community perspectives. As such, health professionals; crises communication professionals, including radio journalists; and disaster-managing stakeholders should be prepared and trained to use humanitarian radio as an integrated part of the disaster health response in natural disasters.
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| 4. |
- Martikainen, Pekka, et al.
(författare)
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Living arrangements of older persons in 1987-2035 in Finland : trends by age, sex and educational attainment
- 2019
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Ingår i: Ageing & Society. - 0144-686X .- 1469-1779. ; 39:2, s. 358-380
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Tidskriftsartikel (refereegranskat)abstract
- Changes in household structure may have a major impact on the future wellbeing of older people. We evaluate changes in living arrangements of 65+ Finnish men and women from 1987 to 2011 and project living arrangements to 2035 by education level. We use an 11 per cent longitudinal sample of Finns drawn from the population registration data. We estimate proportions in various living arrangements and multi-state life table estimates of years lived in particular states. Projections are based on dynamic transition probability forecasts with constant and changing rates. We show that women more than men tend to live alone at older ages. These proportions are likely to start to decline slowly among women, particularly at 80+, but increase or stabilise among men. Apart from living with a marital or co-habiting partner, other living arrangements are growing increasingly rare. The number of basic educated older people is declining rapidly. Educational differences in living arrangements are modest among women, but among men living with a partner is more common among the higher educated. Future living arrangements of older people are strongly determined by past partnership behaviour and future changes in mortality. If life expectancy differences between men and women continue to converge, so will sex differences in the remaining years of life spent living with a partner.
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| 5. |
- Nicolas, Aude, et al.
(författare)
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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
- 2018
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Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
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Tidskriftsartikel (refereegranskat)abstract
- To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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