| 1. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 3. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 4. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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| 5. |
- Johansson, Åke, et al.
(författare)
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A geochronological review of magmatism along the external margin of Columbia and in the Grenville-age orogens forming the core of Rodinia
- 2022
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Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268 .- 1872-7433. ; 371, s. 1-43
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Tidskriftsartikel (refereegranskat)abstract
- A total of 4344 magmatic U-Pb ages in the range 2300 to 800 Ma have been compiled from the Great Proterozoic Accretionary Orogen along the margin of the Columbia / Nuna supercontinent and from the subsequent Grenvillian collisional orogens forming the core of Rodinia. The age data are derived from Laurentia (North America and Greenland, n = 1212), Baltica (NE Europe, n = 1922), Amazonia (central South America, n = 625), Kalahari (southern Africa and Dronning Maud Land in East Antarctica, n = 386), and western Australia (n = 199). Laurentia, Baltica, and Amazonia (and possibly other cratons) most likely formed a ca. 10 000-km-long external active continental margin of Columbia from its assembly at ca. 1800 Ma until its dispersal at ca. 1260 Ma, after which all cratons studied were involved in the Rodinia-forming Grenvillian orogeny. However, the magmatic record is not smooth and even but highly irregular, with marked peaks and troughs, both for individual cratons and the combined data set. Magmatic peaks typically range in duration from a few tens of million years up to around hundred million years, with intervening troughs of comparable length. Some magmatic peaks are observed on multiple cratons, either by coincidence or because of paleogeographic proximity and common tectonic setting, while others are not. The best overall correlation, 0.617, is observed between Baltica and Amazonia, consistent with (but not definitive proof of) their being close neighbours in a SAMBA-like configuration at least in Columbia, and perhaps having shared the same peri-Columbian subduction system for a considerable time. Correlation factors between Laurentia and Baltica, or Laurentia and Amazonia, are below 0.14. Comparison between the Grenville Province in northeastern Laurentia and the Sveconorwegian Province in southwestern Fennoscandia (Baltica) shows some striking similarities, especially in the Mesoproterozoic, but also exhibits differences in the timing of events, especially during the final Grenville-Sveconorwegian collision, when the Sveconorwegian evolution seems to lag behind by some tens of million years. Between the other cratons, the evolution before and during the final Grenvillian collision is also largely diachronous. After 900 Ma, magmatic activity had ceased in all areas investigated, attesting to the position of most of them within the stable interior of Rodinia.
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| 6. |
- Ribeiro, Angela M., et al.
(författare)
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31 degrees South : The physiology of adaptation to arid conditions in a passerine bird
- 2019
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 28:16, s. 3709-3721
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Tidskriftsartikel (refereegranskat)abstract
- Arid environments provide ideal ground for investigating the mechanisms of adaptive evolution. High temperatures and low water availability are relentless stressors for many endotherms, including birds; yet birds persist in deserts. While physiological adaptation probably involves metabolic phenotypes, the underlying mechanisms (plasticity, genetics) are largely uncharacterized. To explore this, we took an intraspecific approach that focused on a species that is resident over a mesic to arid gradient, the Karoo scrub-robin (Cercotrichas coryphaeus). Specifically, we integrated environmental (climatic and primary productivity), physiological (metabolic rates: a measure of energy expenditure), genotypic (genetic variation underlying the machinery of energy production) and microbiome (involved in processing food from where energy is retrieved) data, to infer the mechanism of physiological adaptation. We that found the variation in energetic physiology phenotypes and gut microbiome composition are associated with environmental features as well as with variation in genes underlying energy metabolic pathways. Specifically, we identified a small list of candidate adaptive genes, some of them with known ties to relevant physiology phenotypes. Together our results suggest that selective pressures on energetic physiology mediated by genes related to energy homeostasis and possibly microbiota composition may facilitate adaptation to local conditions and provide an explanation to the high avian intraspecific divergence observed in harsh environments.
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| 7. |
- Savitski, Dzmitry, et al.
(författare)
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Advanced Control Functions Of Decoupled Electro-Hydraulic Brake System
- 2016
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Ingår i: 2016 IEEE 14TH INTERNATIONAL WORKSHOP ON ADVANCED MOTION CONTROL (AMC). - : IEEE. - 9781479984640 ; , s. 310-317
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Konferensbidrag (refereegranskat)abstract
- The paper presents results of analytical and experimental investigations on advanced control functions of decoupled electro-hydraulic brake system. These functions address continuous wheel slip control, variation of the brake pedal feel, and brake judder compensation. The performed study demonstrates that the electro-hydraulic brake system has improved performance by relevant criteria of safety and driving comfort both for conventional and electric vehicles.
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