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- Lee, James J, et al.
(författare)
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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
- 2018
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121
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Tidskriftsartikel (refereegranskat)abstract
- Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
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| 5. |
- Gazdagh, Gabriella, et al.
(författare)
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Extending the phenotypes associated with TRIO gene variants in a cohort of 25 patients and review of the literature
- 2023
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Ingår i: American Journal of Medical Genetics. Part A. - : Wiley-Blackwell. - 1552-4825 .- 1552-4833. ; 191:7, s. 1722-1740
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Forskningsöversikt (refereegranskat)abstract
- The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature. Here, we report an additional 25, previously unreported individuals who possess heterozygous TRIO variants and we review the literature. In addition, functional studies were performed on the c.4394A > G (N1465S) and c.6244-2A > G TRIO variants to provide evidence for their pathogenicity. Variants reported by the current study include missense variants, truncating nonsense variants, and an intragenic deletion. Clinical features were previously described and included developmental delay, learning difficulties, microcephaly, macrocephaly, seizures, behavioral issues (aggression, stereotypies), skeletal problems including short, tapering fingers and scoliosis, dental problems (overcrowding/delayed eruption), and variable facial features. Here, we report clinical features that have not been described previously, including specific structural brain malformations such as abnormalities of the corpus callosum and ventriculomegaly, additional psychological and dental issues along with a more recognizable facial gestalt linked to the specific domains of the TRIO gene and the effect of the variant upon the function of the encoded protein. This current study further strengthens the genotype-to-phenotype correlation that was previously established and extends the range of phenotypes to include structural brain abnormalities, additional skeletal, dental, and psychiatric issues.
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| 6. |
- Hoffmann, R., et al.
(författare)
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Implications of Glacial Melt-Related Processes on the Potential Primary Production of a Microphytobenthic Community in Potter Cove (Antarctica)
- 2019
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 6:October
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Tidskriftsartikel (refereegranskat)abstract
- The Antarctic Peninsula experiences a fast retreat of glaciers, which results in an increased release of particles and sedimentation and, thus, a decrease in the available photosynthetic active radiation (PAR, 400-700 nm) for benthic primary production. In this study, we investigated how changes in the general sedimentation and shading patterns affect the primary production by benthic microalgae, the microphytobenthos. In order to determine potential net primary production and respiration of the microphytobenthic community, sediment cores from locations exposed to different sedimentation rates and shading were exposed to PAR of 0-70 mu.mol photons m(-2)s(-1). Total oxygen exchange rates and microphytobenthic diatom community structure, density, and biomass were determined. Our study revealed that while the microphytobenthic diatom density and composition remained similar, the net primary production of the microphytobenthos decreased with increasing sedimentation and shading. By comparing our experimental results with in situ measured PAR intensities, we furthermore identified microphytobenthic primary production as an important carbon source within Potter Cove's benthic ecosystem. We propose that the microphytobenthic contribution to the total primary production may drop drastically due to Antarctic glacial retreat and related sedimentation and shading, with yet unknown consequences for the benthic heterotrophic community, its structure, and diversity.
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- Roleda, Michael Y., et al.
(författare)
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Photosynthetic performance, DNA damage and repair in gametes of the endemic Antarctic brown alga Ascoseira mirabilis exposed to ultraviolet radiation
- 2007
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Ingår i: Austral Ecology. - : Wiley. - 1442-9985 .- 1442-9993. ; 32:8, s. 917-926
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Tidskriftsartikel (refereegranskat)abstract
- Stress physiology on the reproductive cells of Antarctic macroalgae remained unstudied. Ascoseira mirabilis is endemic to the Antarctic region, an isolated ecosystem exposed to extreme environmental conditions. Moreover, stratospheric ozone depletion leads to increasing ultraviolet radiation (280-400 nm) at the earth's surface, thus it is necessary to investigate the capacity of reproductive cells to cope with different UV irradiances. This study is aimed to investigate the impact of exposure to different spectral irradiance on the photosynthetic performance, DNA damage and gamete morphology of the A. mirabilis. Gametangia, gametes and zygotes of the upper sublittoral brown alga A. mirabilis were exposed to photosynthetically active radiation (PAR = P; 400-700 nm), P + UV-A radiation (UV-A, 320-400 nm) and P + UV-A + UV-B radiation (UV-B, 280-320 nm). Rapid photosynthesis versus irradiance curves of freshly released propagules were measured. Photosynthetic efficiencies and DNA damage (in terms of cyclobutane pyrimidine dimers) were determined after 1, 2, 4 and 8 h exposure as well as after 2 days of recovery in dim white light. Saturation irradiance (I-k) in freshly released propagules was 52 mu mol photons m(-2) s(-1). Exposure for 1 h under 22 mu mol photons m(-2) s(-1) of PAR significantly reduced the optimum quantum yield (F-v/F-m), suggesting that propagules are low light adapted. Furthermore, UVR significantly contributed to the photoinhibition of photosynthesis. Increasing dose as a function of exposure time additionally exacerbated the effects of different light treatments. The amount of DNA damage increased with the UV-B dose but an efficient repair mechanism was observed in gametes pre-exposed to a dose lower than 5.8 x 10(3) J m(-2) of UV-B. The results of this study demonstrate the negative impact of UV-B radiation. However, gametes of A. mirabilis are capable of photosynthetic recovery and DNA repair when the stress factor is removed. This capacity was observed to be dependent on the fitness of the parental sporophyte.
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| 9. |
- Roleda, Michael Y., et al.
(författare)
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Susceptibility of spores of different ploidy levels from Antarctic Gigartina skottsbergii (Gigartinales, Rhodophyta) to ultraviolet radiation
- 2008
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Ingår i: Phycologia. - 0031-8884. ; 47:4, s. 361-370
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Tidskriftsartikel (refereegranskat)abstract
- Haploid tetraspores and diploid carpospores from Antarctic Gigartina skottsbergii were exposed in the laboratory to photosynthetically active radiation (400-700 nm = P), P + ultraviolet (UV)-A radiation (320-700 nm = PA) and P + UV-A + UV-B radiation (280-700 nm = PAB). Photosynthetic performance, DNA damage and repair, spore mortality, and an initial characterization of the UV-absorbing mycosporine-like amino acids (MAAs) were studied. Rapid photosynthesis vs irradiance (E) curves of freshly released spores showed that both tetraspores and carpospores were low-light adapted (E-k = 44 +/- 2 and 54 +/- 2 mu mol photons m(-2) s(-1), respectively). The light-harvesting and photosynthetic conversion efficiencies were similar (alpha = 0.13), whereas photosynthetic capacity in terms of optimum quantum yield (F-v/F-m) and relative electron transport rate (rETR(max)) were significantly higher in carpospores. Photoinhibition and recovery of photosynthesis were not significantly different between spore ploidy but were significantly affected by radiation and exposure time treatments. Accumulation of DNA damage was UV-B dose dependent and significantly higher in tetraspores than in carpospores. After 2 days postcultivation, DNA lesions were completely repaired in spores exposed to UV-B dose less than 1.2 X 10(4) J m(-2). The dynamic recovery of photosynthetic capacity as well as effective DNA repair mechanism contributed to the relatively low spore mortality (4-14%). A substantial amount of UV-screening MAAs shinorine and palythine were observed for the first time in spores of Gigartinales. This study on stress and physiological characterization of seaweed propagules is important to understand recruitment dynamics and life history phase dominance in the field.
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