| 1. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 2. |
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| 3. |
- Silva, C. N. S., et al.
(author)
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Insights into the genetic architecture of morphological traits in two passerine bird species
- 2017
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In: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 119:3, s. 197-205
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Journal article (peer-reviewed)abstract
- Knowledge about the underlying genetic architecture of phenotypic traits is needed to understand and predict evolutionary dynamics. The number of causal loci, magnitude of the effects and location in the genome are, however, still largely unknown. Here, we use genome-wide single-nucleotide polymorphism (SNP) data from two large-scale data sets on house sparrows and collared flycatchers to examine the genetic architecture of different morphological traits (tarsus length, wing length, body mass, bill depth, bill length, total and visible badge size and white wing patches). Genomic heritabilities were estimated using relatedness calculated from SNPs. The proportion of variance captured by the SNPs (SNP-based heritability) was lower in house sparrows compared with collared flycatchers, as expected given marker density (6348 SNPs in house sparrows versus 38 689 SNPs in collared flycatchers). Indeed, after downsampling to similar SNP density and sample size, this estimate was no longer markedly different between species. Chromosome-partitioning analyses demonstrated that the proportion of variance explained by each chromosome was significantly positively related to the chromosome size for some traits and, generally, that larger chromosomes tended to explain proportionally more variation than smaller chromosomes. Finally, we found two genome-wide significant associations with very small-effect sizes. One SNP on chromosome 20 was associated with bill length in house sparrows and explained 1.2% of phenotypic variation (V-P), and one SNP on chromosome 4 was associated with tarsus length in collared flycatchers (3% of V-P). Although we cannot exclude the possibility of undetected large-effect loci, our results indicate a polygenic basis for morphological traits.
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| 4. |
- Bushuev, A. V., et al.
(author)
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Quantitative genetics of basal metabolic rate and body mass in free-living pied flycatchers
- 2012
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In: Journal of Zoology. - : Wiley. - 0952-8369 .- 1469-7998. ; 288:4, s. 245-251
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Journal article (peer-reviewed)abstract
- Despite basal metabolic rate (BMR) being one of the most commonly measured physiological traits and an important indicator of competitive ability, very little is known about its genetic basis and relation to other physiological traits. Here, we present the first attempt to estimate the multivariate basis of BMR using a natural population of pied flycatcher Ficedula hypoleuca breeding in the Tomsk Region, Western Siberia. We show relatively high and significant heritability of whole-organism BMR, mass-specific BMR and mass-independent BMR (h 2 = 0.43, 0.55 and 0.52, respectively), which indicates the potential of these energetic traits to respond to direct selection. In contrast to some previous reports, we found that the genetic correlations between body mass and all three measures of BMR were not significantly different from zero. Independent evolution of body mass and BMR in this species should therefore be possible. Following a previous report, we also estimated the genetic correlations between the different BMR measures and show they are all close to unity, suggesting that they are, from a genetic point of view, a similar trait. Our results are in contrast with previous studies measuring the genetic basis of metabolic rates using aviary-bred birds and highlight the importance of considering BMR in a natural setting.
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| 5. |
- Dahl, Mette, et al.
(author)
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Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma : a study of younger patients from the MCL2 and MCL3 clinical trials
- 2022
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In: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 36:1, s. 177-188
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Journal article (peer-reviewed)abstract
- Mantle cell lymphoma (MCL) is characterized by marked differences in outcome, emphasizing the need for strong prognostic biomarkers. Here, we explore expression patterns and prognostic relevance of circular RNAs (circRNAs), a group of endogenous non-coding RNA molecules, in MCL. We profiled the circRNA expression landscape using RNA-sequencing and explored the prognostic potential of 40 abundant circRNAs in samples from the Nordic MCL2 and MCL3 clinical trials, using NanoString nCounter Technology. We report a circRNA-based signature (circSCORE) developed in the training cohort MCL2 that is highly predictive of time to progression (TTP) and lymphoma-specific survival (LSS). The dismal outcome observed in the large proportion of patients assigned to the circSCORE high-risk group was confirmed in the independent validation cohort MCL3, both in terms of TTP (HR 3.0; P = 0.0004) and LSS (HR 3.6; P = 0.001). In Cox multiple regression analysis incorporating MIPI, Ki67 index, blastoid morphology and presence of TP53 mutations, circSCORE retained prognostic significance for TTP (HR 3.2; P = 0.01) and LSS (HR 4.6; P = 0.01). In conclusion, circRNAs are promising prognostic biomarkers in MCL and circSCORE improves identification of high-risk disease among younger patients treated with cytarabine-containing chemoimmunotherapy and autologous stem cell transplant.
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| 6. |
- Eskelund, Christian W., et al.
(author)
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15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2) : prolonged remissions without survival plateau
- 2016
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 175:3, s. 410-418
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Journal article (peer-reviewed)abstract
- In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen, developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 114years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 127 and 85years, respectively. The MCL International Prognostic Index (MIPI), biological MIPI, including Ki67 expression (MIPI-B) and the MIPI-B including mIR-18b expression (MIPI-B-miR), in particular, significantly divided patients into distinct risk groups. Despite very long response durations of the low and intermediate risk groups, we observed a continuous pattern of relapse and the survival curves never reached a plateau. In conclusion, despite half of the patients being still alive and 40% in first remission after more than 12years, we still see an excess disease-related mortality, even among patients experiencing long remissions. Even though we consider the Nordic regimen as a very good choice of regimen, we recommend inclusion in prospective studies to explore the benefit of novel agents in the frontline treatment of MCL.
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| 7. |
- Eskelund, Christian Winther, et al.
(author)
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Clonal hematopoiesis evolves from pretreatment clones and stabilizes after end of chemotherapy in patients with MCL
- 2020
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 135:22, s. 2000-2004
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Journal article (other academic/artistic)abstract
- Eskelund et al examined clonal hematopoiesis (CH) in a cohort of patients with mantle cell lymphoma (MCL) treated with first-line chemotherapy and autologous stem cell transplantation. In young, good-risk MCL patients, CH after first-line therapy arises almost entirely from preexisting clones, stabilizes after a period of expansion posttransplantation, and does not negatively impact survival.
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| 8. |
- Eskelund, Christian W., et al.
(author)
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TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy
- 2017
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 130:17, s. 1903-1910
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Journal article (peer-reviewed)abstract
- Despite recent advances in lymphoma treatment, mantle cell lymphoma (MCL) remains incurable, and we are still unable to identify patients who will not benefit from the current standard of care. Here, we explore the prognostic value of recurrent genetic aberrations in diagnostic bone marrow (BM) specimens from 183 younger patients with MCL from the Nordic MCL2 and MCL3 trials, which represent current standard-of-care regimens. In the univariate model, mutations of TP53 (11%) and NOTCH1 (4%), and deletions of TP53 (16%) andCDKN2A(20%),weresignificantly associatedwithinferioroutcomes(togetherwithMIPI, MIPI-c, blastoidmorphology, and Ki67 > 30%); however, inmultivariate analyses, only TP53 mutations (HR, 6.2; P <.0001) retained prognostic impact for overall survival (OS), whereas TP53 mutations (HR, 6.9; P <.0001) andMIPI-c high-risk (HR, 2.6; P5.003) had independent prognostic impact on time to relapse. TP53-mutated cases had a dismal outcome, with a median OS of 1.8 years, and 50% relapsed at 1.0 years, compared to a median OS of 12.7 years for TP53-unmutated cases (P <.0001). TP53 mutations were significantly associated with Ki67 > 30%, blastoid morphology, MIPI high-risk, and inferior responses to both induction- and high-dose chemotherapy. In conclusion, we show that TP53mutations identify a phenotypically distinct and highly aggressive form of MCL with poor or no response to regimens including cytarabine, rituximab, and autologous stem-cell transplant (ASCT). We suggest patients with MCL should be stratified according to TP53 status, and that patients with TP53 mutations should be considered for experimental frontline trials exploring novel agents.
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| 9. |
- Fountain, Toby, et al.
(author)
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Inferring dispersal across a fragmented landscape using reconstructed families in the Glanville fritillary butterfly
- 2018
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In: Evolutionary Applications. - : Wiley. - 1752-4571. ; 11:3, s. 287-297
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Journal article (peer-reviewed)abstract
- Dispersal is important for determining both species ecological processes, such as population viability, and its evolutionary processes, like gene flow and local adaptation. Yet obtaining accurate estimates in the wild through direct observation can be challenging or even impossible, particularly over large spatial and temporal scales. Genotyping many individuals from wild populations can provide detailed inferences about dispersal. We therefore utilized genomewide marker data to estimate dispersal in the classic metapopulation of the Glanville fritillary butterfly (Melitaea cinxia L.), in the Åland Islands in SW Finland. This is an ideal system to test the effectiveness of this approach due to the wealth of information already available covering dispersal across small spatial and temporal scales, but lack of information at larger spatial and temporal scales. We sampled three larvae per larval family group from 3732 groups over a six-year period and genotyped for 272 SNPs across the genome. We used this empirical data set to reconstruct cases where full-sibs were detected in different local populations to infer female effective dispersal distance, that is, dispersal events directly contributing to gene flow. On average this was one kilometre, closely matching previous dispersal estimates made using direct observation. To evaluate our power to detect full-sib families, we performed forward simulations using an individual-based model constructed and parameterized for the Glanville fritillary metapopulation. Using these simulations, 100% of predicted full-sibs were correct and over 98% of all true full-sib pairs were detected. We therefore demonstrate that even in a highly dynamic system with a relatively small number of markers, we can accurately reconstruct full-sib families and for the first time make inferences on female effective dispersal. This highlights the utility of this approach in systems where it has previously been impossible to obtain accurate estimates of dispersal over both ecological and evolutionary scales.
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| 10. |
- Grepstad, J. K., et al.
(author)
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As capping of MBE-grown compound semiconductors; novel opportunities to interface science and device fabrication
- 1994
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In: Physica Scripta. - 0031-8949. ; 1994:T54, s. 216-225
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Journal article (peer-reviewed)abstract
- In situ condensation of an amorphous cap of the high vapour pressure element (i.e. As, Sb) has been found to provide effective protection of molecular beam epitaxy grown compound semiconductor surfaces against ambient contamination. Most work reported so far relates to arsenic-capped AlGaAs. Detailed investigation with surface sensitive structural (RHEED, LEED) and chemical (XPS) probes confirms that the protective cap is conveniently removed by annealing in ultrahigh vaccum environments at a temperature in excess of similar 350 °C. Clean AlxGa1-xAs(001) surfaces with different atomic reconstructions and corresponding (Al)Ga: As composition ratios are now routinely prepared by this technique, and thus offers an ideal testing ground for compound semiconductor surface and interface research. Reconstruction-dependent reactivity at metal/GaAs(001) interfaces is demonstrated, using surface sensitive synchrotron radiation photoelectron spectroscopy. Exploiting the protection offered by the As (Sb) cap for device fabrication purposes (e.g. in selective area epitaxy), demands a suitable method of pattern definition in the amorphous arsenic layer. The cap is shown to be chemically stable versus exposure to standard photolithographic processing chemicals, including photoresist, developer, and acetone (the photoresist solvent). However, the temperature required for thermal decapping is grossly inappropriate for photoresist curing. A novel technique of reactive decapping in a beam of hydrogen radicals (H‒) is shown to be effective at room temperature. This innovation makes pattern definition in the As cap compatible with standard photolithography, and test structures with similar 5 μm linewidth is demonstrated. Scanning electron micrographs unveil the presence of arsenic cap residues along the photoresist mask edges. Moreover, trace amounts of surface gallium oxide and carbon impurities were found with core-level photoelectron spectroscopy. The technique thus needs further refinement, before being useful in fabrication of compound semiconductor device structures.
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