| 11. |
- Oddsson, Asmundur, et al.
(författare)
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Deficit of homozygosity among 1.52 million individuals and genetic causes of recessive lethality
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. To explore genetic causes of recessive lethality, we searched for sequence variants with deficit of homozygosity among 1.52 million individuals from six European populations. In this study, we identified 25 genes harboring protein-altering sequence variants with a strong deficit of homozygosity (10% or less of predicted homozygotes). Sequence variants in 12 of the genes cause Mendelian disease under a recessive mode of inheritance, two under a dominant mode, but variants in the remaining 11 have not been reported to cause disease. Sequence variants with a strong deficit of homozygosity are over-represented among genes essential for growth of human cell lines and genes orthologous to mouse genes known to affect viability. The function of these genes gives insight into the genetics of intrauterine lethality. We also identified 1077 genes with homozygous predicted loss-of-function genotypes not previously described, bringing the total set of genes completely knocked out in humans to 4785.
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| 12. |
- Pattaro, Cristian, et al.
(författare)
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Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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| 13. |
- Piltti, Juha, 1982-, et al.
(författare)
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Proteomics of chondrocytes with special reference to phosphorylation changes of proteins in stretched human chondrosarcoma cells.
- 2008
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Ingår i: Biorheology. - : IOS Press. - 0006-355X .- 1878-5034. ; 45:3-4, s. 323-335
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Tidskriftsartikel (refereegranskat)abstract
- For proteomic analysis, cartilage molecular composition is a challenging mixture of highly glycosylated proteoglycans and triple-helical collagens, which constitute the major part of cartilage macromolecules. Selective separation of these molecules from the minor components is generally needed before mass spectrometry-based identification of lower-abundancy proteins is possible. The cell density of cartilage is also very low, therefore, cell cultures offer an easier approach to study cellular responses of chondrocytic cells, e.g., to mechanical stimuli. In this study, we investigated the phosphorylation events in human chondrosarcoma cells during cellular stretching. Human chondrosarcoma cells were stretched to 8% strain at a frequency of 1 Hz. One set of experiments included cellular stretching which lasted 2 hours, and the other one included experiments of 2 hours daily treatment for up to 3 days. Two-dimensional polyacrylamide gel electrophoresis combined with chromatographic phosphoprotein pre-enrichment and electrospray ionization mass spectrometry-based protein identification was used to reveal changes of phosphoproteins in cells exposed to cyclic stretching. We discovered that 2 hours cyclic stretching increased the phosphorylation of moesin, elongation factor eEF1D and leprecan, while the phosphorylation of elongation factor eEF1B decreased after cellular stretching. Western blot analyses with phospho-specific antibodies suggested that stretching induces phosphorylation of ERK of the MAP kinase pathway, but did not induce phosphorylation of phosphatidylinositol 3-kinase. In conclusion, the proteomic approach revealed that cellular stretching induced specific phosphorylation changes in chondrosarcoma cells.
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| 14. |
- Roslin, Tomas, et al.
(författare)
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A molecular-based identification resource for the arthropods of Finland
- 2022
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 22:2, s. 803-822
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Tidskriftsartikel (refereegranskat)abstract
- To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.
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| 15. |
- Somani, M. C., et al.
(författare)
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Influence of composition and prior deformation on phase transformation temperatures and hardness in direct quenching using physical simulation
- 2015
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Ingår i: Materials Performance and Characterization. - : ASTM International. - 2379-1365 .- 2165-3992. ; 4:3, s. 341-364
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Tidskriftsartikel (refereegranskat)abstract
- For conventional reheated and quenched (RQ) steels, the level of alloying necessary to achieve a given hardenability and hardness can be estimated from calculated Jominy curves or ideal critical diameters (DI) given in ASTM A255-10(2014). However, for thermomechanically rolled direct quenched (DQ) steels, little data are available. In this study, the accuracy of the ASTM approach was estimated by designing an experiment to study the main effects of seven alloying elements (C, Mn, Cr, Ni, Mo, Nb, and V) at two levels with eight boron steels based on an eight-run resolution III partial factorial designed experiment. Continuous cooling transformation (CCT) diagrams covering cooling rates of 1.5°C/s-48°C/s were determined using Gleeble simulations with or without controlled deformation below Tnr. The effects of deformation below Tnr and the alloying elements were clearly revealed. In general, low temperature straining of the austenite led to higher levels of hardness than quenching from unstrained austenite. The start of the bainite transformation Ar3 (bainite) was modelled as a function of chemical composition and cooling rate. The data in the CCT diagrams were used to derive equivalent ideal critical diameters (DIB) for strained and unstrained prior austenite. The hardenability index DIB calculated from experimental Jominy curves generally agreed well with those of CCT data for unstrained austenite. In order to apply the ASTM A255 approach to the calculation of DIB, boron factors (BF) for steels with alloy factors (AFs) greater than 26 were estimated by extrapolating the ASTM data. However, this approach did not give satisfactory predictions for either strained or unstrained austenite. Preliminary analysis indicated that Cr, Mo, and V might be less effective at increasing hardenability than implied from their AFs. New formulae were given to allow estimations of the hardness to be expected in connection with direct quenching.
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| 16. |
- Strausz, Satu, et al.
(författare)
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Genetic analysis of obstructive sleep apnoea discovers a strong association with cardiometabolic health
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:5, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- There is currently limited understanding of the genetic aetiology of obstructive sleep apnoea (OSA). We aimed to identify genetic loci associated with OSA risk, and to test if OSA and its comorbidities share a common genetic background. We conducted the first large-scale genome-wide association study of OSA using the FinnGen study (217 955 individuals) with 16 761 OSA patients identified using nationwide health registries. We estimated 0.08 (95% CI 0.06.0.11) heritability and identified five loci associated with OSA (p<5.0×10-8): rs4837016 near GAPVD1 (GTPase activating protein and VPS9 domains 1), rs10928560 near CXCR4 (C-X-C motif chemokine receptor type 4), rs185932673 near CAMK1D (calcium/calmodulindependent protein kinase ID) and rs9937053 near FTO (fat mass and obesity-associated protein; a variant previously associated with body mass index (BMI)). In a BMI-adjusted analysis, an association was observed for rs10507084 near RMST/NEDD1 (rhabdomyosarcoma 2 associated transcript/NEDD1 γ-tubulin ring complex targeting factor). We found high genetic correlations between OSA and BMI (rg=0.72 (95% CI 0.62-0.83)), and with comorbidities including hypertension, type 2 diabetes, coronary heart disease, stroke, depression, hypothyroidism, asthma and inflammatory rheumatic disease (rg>0.30). The polygenic risk score for BMI showed 1.98-fold increased OSA risk between the highest and the lowest quintile, and Mendelian randomisation supported a causal relationship between BMI and OSA. Our findings support the causal link between obesity and OSA, and the joint genetic basis between OSA and comorbidities.
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| 17. |
- Woolway, R. Iestyn, et al.
(författare)
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Geographic and temporal variations in turbulent heat loss from lakes : A global analysis across 45 lakes
- 2018
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Ingår i: Limnology and Oceanography. - : WILEY. - 0024-3590 .- 1939-5590. ; 63:6, s. 2436-2449
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Tidskriftsartikel (refereegranskat)abstract
- Heat fluxes at the lake surface play an integral part in determining the energy budget and thermal structure in lakes, including regulating how lakes respond to climate change. We explore patterns in turbulent heat fluxes, which vary across temporal and spatial scales, using in situ high-frequency monitoring data from 45 globally distributed lakes. Our analysis demonstrates that some of the lakes studied follow a marked seasonal cycle in their turbulent surface fluxes and that turbulent heat loss is highest in larger lakes and those situated at low latitude. The Bowen ratio, which is the ratio of mean sensible to mean latent heat fluxes, is smaller at low latitudes and, in turn, the relative contribution of evaporative to total turbulent heat loss increases toward the tropics. Latent heat transfer ranged from similar to 60% to > 90% of total turbulent heat loss in the examined lakes. The Bowen ratio ranged from 0.04 to 0.69 and correlated significantly with latitude. The relative contributions to total turbulent heat loss therefore differ among lakes, and these contributions are influenced greatly by lake location. Our findings have implications for understanding the role of lakes in the climate system, effects on the lake water balance, and temperature-dependent processes in lakes.
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| 18. |
- Zhou, Wei, et al.
(författare)
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Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
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Ingår i: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
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