| 1. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
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Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 2. |
- Kuderna, Lukas F. K., et al.
(författare)
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A global catalog of whole-genome diversity from 233 primate species
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
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Tidskriftsartikel (refereegranskat)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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| 3. |
- Kuderna, Lukas F. K., et al.
(författare)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 4. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 5. |
- Torkzad, Michael R., et al.
(författare)
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The Clinical Perspective on Value of 3D, Thin Slice T2-Weighted Images in 3T Pelvic MRI for Tumors
- 2012
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Ingår i: Current Medical Imaging Reviews. - : Bentham Science Publishers Ltd.. - 1573-4056. ; 8:2, s. 76-81(6)
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Tidskriftsartikel (refereegranskat)abstract
- Pelvic imaging is undergoing rapid changes due to increased use of 3-Tesla (3T) magnetic resonance imaging (3T MRI). One of the advantages of 3T could be the possibility for thin section 3-dimensional (3D) imaging which could improve accuracy and at the same time reduce the need for multi-planar imaging needed for conventional T2 imaging (TSE). In the following text we review the advantages of 3D thin section imaging for assessment of pelvic tumors.
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| 6. |
- Abdelmagid, N., et al.
(författare)
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The Calcitonin Receptor Gene Is a Candidate for Regulation of Susceptibility to Herpes simplex Type 1 Neuronal Infection Leading to Encephalitis in Rat
- 2012
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Ingår i: Plos Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Herpes simplex encephalitis (HSE) is a fatal infection of the central nervous system (CNS) predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s) regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL), Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5) governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr) as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.
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| 7. |
- Akselsson, Roland, et al.
(författare)
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Multidisciplinary Research on Integration of Human Factors and Production Concepts such as TQM - A Participatory Discussion Session
- 1999
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Ingår i: Proceedings of the Conference on TQM and Human Factors. - 9172195207 ; 2, s. 439-448
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Konferensbidrag (refereegranskat)abstract
- A discussion session where the conference participants are invited to participate is planned. One topic for the session is to discuss experiences of multidisciplinary research on integration of human factors and different production concepts applied in change processes within Swedish companies. An important question that the discussion will focus on is: How to get high quality in multidisciplinary research? Another topic is to discuss how people from different disciplines in the companies interact with each other and with the researchers. Researchers from the centre Change@Work at Lund University in Sweden will present some of their experiences from several years of multidisciplinary research in companies. As a background the research questions within Change@Work are presented below. Discussions during the workshop will be performed according to methods used by the researchers in their research in the companies. All discussion will be documented and later sent to all workshop participants.
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| 8. |
- Al Nimer, Faiez, et al.
(författare)
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Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination
- 2016
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Ingår i: Neurology. - 2332-7812. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. Methods: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study comparing patients with MS (n = 147) with controls (n = 50) and patients with relapsing-remitting MS (n = 75) with patients with progressive MS (n = 72); (2) in CSF and brain tissue microdialysates from a case series of 7 patients with progressive MS; and (3) in CSF at baseline and 60 weeks after natalizumab treatment in a cohort study of 17 patients with progressive MS. Correlation to neurofilament light, a marker of neuroaxonal injury, was tested. The effect of LCN2 on myelination and neurodegeneration was studied in a rat in vitro neuroglial cell coculture model. Results: Intrathecal production of LCN2 was increased predominantly in patients with progressive MS (p < 0.005 vs relapsing-remitting MS) and displayed a positive correlation to neurofilament light (p = 0.005). Levels of LCN2 in brain microdialysates were severalfold higher than in the CSF, suggesting local production in progressive MS. Treatment with natalizumab in progressive MS reduced LCN2 levels an average of 13% (p < 0.0001). LCN2 was found to inhibit remyelination in a dose-dependent manner in vitro. Conclusions: LCN2 production is predominantly increased in progressive MS. Although this moderate increase does not support the use of LCN2 as a biomarker, the correlation to neurofilament light and the inhibitory effect on remyelination suggest that LCN2 might contribute to neurodegeneration through myelination-dependent pathways.
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| 9. |
- Ambrosi, Aurelie, et al.
(författare)
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Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern
- 2012
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Ingår i: Annals of the Rheumatic Diseases. - London : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 71:3, s. 334-340
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Tidskriftsartikel (refereegranskat)abstract
- Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.
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