| 1. |
- Guichard, Etienne, et al.
(författare)
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Impact of non-LTR retrotransposons in the differentiation and evolution of anatomically modern humans
- 2018
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Ingår i: Mobile DNA. - : BMC. - 1759-8753. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transposable elements are biologically important components of eukaryote genomes. In particular, non-LTR retrotransposons (N-LTRrs) played a key role in shaping the human genome throughout evolution. In this study, we compared retrotransposon insertions differentially present in the genomes of Anatomically Modern Humans, Neanderthals, Denisovans and Chimpanzees, in order to assess the possible impact of retrotransposition in the differentiation of the human lineage. Results: We first identified species-specific N-LTRrs and established their distribution in present day human populations. These analyses shortlisted a group of N-LTRr insertions that were found exclusively in Anatomically Modern Humans. These insertions are associated with an increase in the number of transcriptional/splicing variants of those genes they inserted in. The analysis of the functionality of genes containing human-specific N-LTRr insertions reflects changes that occurred during human evolution. In particular, the expression of genes containing the most recent N-LTRr insertions is enriched in the brain, especially in undifferentiated neurons, and these genes associate in networks related to neuron maturation and migration. Additionally, we identified candidate N-LTRr insertions that have likely produced new functional variants exclusive to modern humans, whose genomic loci show traces of positive selection. Conclusions: Our results strongly suggest that N-LTRr impacted our differentiation as a species, most likely inducing an increase in neural complexity, and have been a constant source of genomic variability all throughout the evolution of the human lineage.
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| 2. |
- Ricci, Cristian, et al.
(författare)
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Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke : EPIC-CVD case-cohort study
- 2018
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Ingår i: The BMJ. - : BMJ PUBLISHING GROUP. - 1756-1833 .- 0959-8138. ; 361
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. DESIGN Multicentre case-cohort study. SETTING A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. PARTICIPANTS 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. MAIN OUTCOME MEASURES Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). RESULTS There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/ day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. CONCLUSIONS Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
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| 3. |
- Ricci, Marco, et al.
(författare)
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Transposable Elements Activity is Positively Related to Rate of Speciation in Mammals
- 2018
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Ingår i: Journal of Molecular Evolution. - : Springer. - 0022-2844 .- 1432-1432. ; 86:5, s. 303-310
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Tidskriftsartikel (refereegranskat)abstract
- Transposable elements (TEs) play an essential role in shaping eukaryotic genomes and generating variability. Speciation and TE activity bursts could be strongly related in mammals, in which simple gradualistic models of differentiation do not account for the currently observed species variability. In order to test this hypothesis, we designed two parameters: the Density of insertion (DI) and the Relative rate of speciation (RRS). DI is the ratio between the number of TE insertions in a genome and its size, whereas the RRS is a conditional parameter designed to identify potential speciation bursts. Thus, by analyzing TE insertions in mammals, we defined the genomes as "hot" (high DI) and "cold" (low DI). Then, comparing TE activity among 29 taxonomical families of the whole Mammalia class, 16 intra-order pairs of mammalian species, and four superorders of Eutheria, we showed that taxa with high rates of speciation are associated with "hot" genomes, whereas taxa with low ones are associated with "cold" genomes. These results suggest a remarkable correlation between TE activity and speciation, also being consistent with patterns describing variable rates of differentiation and accounting for the different time frames of the speciation bursts.
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