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- Hakkaart, C, et al.
(författare)
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Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1061-
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09–1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.
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| 7. |
- Green, Leon, et al.
(författare)
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Ancestral Sperm Ecotypes Reveal Multiple Invasions of a Non-Native Fish in Northern Europe
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- For externally fertilising organisms in the aquatic environment, the abiotic fertilisation medium can be a strong selecting force. Among bony fishes, sperm are adapted to function in a narrow salinity range. A notable exception is the family Gobiidae, where several species reproduce across a wide salinity range. The family also contains several wide-spread invasive species. To better understand how these fishes tolerate such varying conditions, we measured sperm performance in relation to salinity from a freshwater and a brackish population within their ancestral Ponto-Caspian region of the round goby, Neogobius melanostomus. These two ancestral populations were then compared to nine additional invaded sites across northern Europe, both in terms of their sperm traits and by using genomic SNP markers. Our results show clear patterns of ancestral adaptations to freshwater and brackish salinities in their sperm performance. Population genomic analyses show that the ancestral ecotypes have generally established themselves in environments that fit their sperm adaptations. Sites close to ports with intense shipping show that both outbreeding and admixture can affect the sperm performance of a population in a given salinity. Rapid adaptation to local conditions is also supported at some sites. Historical and contemporary evolution in the traits of the round goby sperm cells is tightly linked to the population and seascape genomics as well as biogeographic processes in these invasive fishes. Since the risk of a population establishing in an area is related to the genotype by environment match, port connectivity and the ancestry of the round goby population can likely be useful for predicting the species spread.
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| 8. |
- Green, L, et al.
(författare)
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Data supporting: Invader at the edge - genomic origins and physiological differences of round gobies across a steep urban salinity gradient
- 2022
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Annan publikationabstract
- Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread and understanding them is important for management. In Scandinavia’s largest cargo port, the invasive round goby (Neogobius melanostomus), is established across a steep salinity gradient. We used 12 937 SNPs to identify the genetic origin and diversity of three sites along the salinity gradient and round goby from western, central and northern Baltic Sea, as well as north European rivers. Fish from two sites from the extreme ends of the gradient were also acclimated to freshwater and seawater, and tested for respiratory and osmoregulatory physiology. Fish from the high salinity environment in the outer port showed higher genetic diversity, and closer relatedness to the other regions, compared to fish from lower salinity upstream the river. Fish from the high salinity site also had higher maximum metabolic rate, fewer blood cells and lower blood Ca2+. Despite these genotypic and phenotypic differences, salinity acclimation affected fish from both sites in the same way: seawater increased the blood osmolality and Na+ levels, and freshwater increased the levels of the stress hormone cortisol. Our results show genotypic and phenotypic differences over short spatial scales across this steep salinity gradient. These patterns of the physiologically robust round goby are likely driven by multiple introductions into the high salinity site, and a process of sorting, likely based on behaviour or selection, along the gradient. Since this euryhaline fish risks spreading from this area, seascape genomics and phenotypic characterisation can inform management strategies even within an area as small as a coastal harbour inlet.
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| 9. |
- Green, Leon, et al.
(författare)
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Invader at the edge - Genomic origins and physiological differences of round gobies across a steep urban salinity gradient
- 2023
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Ingår i: Evolutionary Applications. - : Wiley. - 1752-4571. ; 16:2, s. 321-37
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Tidskriftsartikel (refereegranskat)abstract
- Species invasions are a global problem of increasing concern, especially in highly connected aquatic environments. Despite this, salinity conditions can pose physiological barriers to their spread, and understanding them is important for management. In Scandinavia's largest cargo port, the invasive round goby (Neogobius melanostomus) is established across a steep salinity gradient. We used 12,937 SNPs to identify the genetic origin and diversity of three sites along the salinity gradient and round goby from western, central and northern Baltic Sea, as well as north European rivers. Fish from two sites from the extreme ends of the gradient were also acclimated to freshwater and seawater, and tested for respiratory and osmoregulatory physiology. Fish from the high-salinity environment in the outer port showed higher genetic diversity, and closer relatedness to the other regions, compared to fish from lower salinity upstream the river. Fish from the high-salinity site also had higher maximum metabolic rate, fewer blood cells and lower blood Ca2+. Despite these genotypic and phenotypic differences, salinity acclimation affected fish from both sites in the same way: seawater increased the blood osmolality and Na+ levels, and freshwater increased the levels of the stress hormone cortisol. Our results show genotypic and phenotypic differences over short spatial scales across this steep salinity gradient. These patterns of the physiologically robust round goby are likely driven by multiple introductions into the high-salinity site, and a process of sorting, likely based on behaviour or selection, along the gradient. This euryhaline fish risks spreading from this area, and seascape genomics and phenotypic characterization can inform management strategies even within an area as small as a coastal harbour inlet.
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| 10. |
- Jansson, E., et al.
(författare)
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Genetic study reveals local differentiation persisting in the face of high connectivity and a genomic inversion likely linked with sexual antagonism in a common marine fish
- 2023
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Ingår i: Ices Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 8:4, s. 1103-12
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Tidskriftsartikel (refereegranskat)abstract
- Sustainable harvest of wild populations requires knowledge of the underlying population structure. The focus of this study is on goldsinny wrasse (Ctenolabrus rupestris), a small marine fish inhabiting coastal waters of the north-eastern Atlantic. This species is caught in large numbers to serve as cleaner fish in salmonid aquaculture. We genotyped 2073 goldsinny wrasse from 43 sites along the Scandinavian coastline with 143 SNPs. Seven of the SNPs were linked and likely reside within a large genomic inversion dominated by one haplotype. The heterokaryotype of the putative inversion displayed sex-specific growth patterns, potentially resolving sexual antagonism for this trait. The unlinked 134 SNPs showed modest isolation-by-distance with samples from the northernmost locations showing highest divergence, whereas sites farther south were much more interconnected. Genetic divergence (F-ST) was highly variable among sites within regions, suggesting a varying degree of connectivity and local divergence. We conclude that despite a high degree of gene-flow mediated through pelagic dispersal in early life stages, regional and some local population structure remains due to limited adult movement in addition to other unidentified factors. Consequently, the species might be more vulnerable to local disturbances than previously anticipated.
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