Conflicting phylogenetic signals in the SlX1/Y1 gene in Silene

<p>Abstract</p> <p>Background</p> <p>Increasing evidence from DNA sequence data has revealed that phylogenies based on different genes may drastically differ from each other. This may be due to either inter- or intralineage processes, or to methodological or stochastic errors. Here we investigate a spectacular case where two parts of the same gene (<it>SlX1</it>/<it>Y1</it>) show conflicting phylogenies within <it>Silene (Caryophyllaceae)</it>. <it>SlX1 </it>and <it>SlY1 </it>are sex-linked genes on the sex chromosomes of dioecious members of <it>Silene </it>sect. <it>Elisanthe</it>.</p> <p>Results</p> <p>We sequenced the homologues of the <it>SlX1</it>/<it>Y1 </it>genes in several <it>Sileneae </it>species. We demonstrate that different parts of the <it>SlX1/Y1 </it>region give different phylogenetic signals. The major discrepancy is that <it>Silene vulgaris </it>and <it>S</it>. sect. <it>Conoimorpha </it>(<it>S. conica </it>and relatives) exchange positions. To determine whether gene duplication followed by recombination (an intralineage process) may explain the phylogenetic conflict in the <it>Silene SlX1/Y1 </it>gene, we use a novel probabilistic, multiple primer-pair PCR approach. We did not find any evidence supporting gene duplication/loss as explanation to the phylogenetic conflict.</p> <p>Conclusion</p> <p>The phylogenetic conflict in the <it>Silene SlX1/Y1 </it>gene cannot be explained by paralogy or artefacts, such as <it>in vitro </it>recombination during PCR. The support for the conflict is strong enough to exclude methodological or stochastic errors as likely sources. Instead, the phylogenetic incongruence may have been caused by recombination of two divergent alleles following ancient interspecific hybridization or incomplete lineage sorting. These events probably took place several million years ago. This example clearly demonstrates that different parts of the genome may have different evolutionary histories and stresses the importance of using multiple genes in reconstruction of taxonomic relationships.</p

Rationale for a Swedish cohort consortium

We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.Peer reviewe

On Estimating Topology and Divergence Times in Phylogenetics

This PhD thesis consists of an introduction and five papers, dealing with statistical methods in phylogenetics. A phylogenetic tree describes the evolutionary relationships among species assuming that they share a common ancestor and that evolution takes place in a tree like manner. Our aim is to reconstruct the evolutionary relationships from aligned DNA sequences. In the first two papers we investigate two measures of confidence for likelihood based methods, bootstrap frequencies with Maximum Likelihood (ML) and Bayesian posterior probabilities. We show that an earlier claimed approximate equivalence between them holds under certain conditions, but not in the current implementations of the two methods. In the following two papers the divergence times of the internal nodes are considered. The ML estimate of the divergence time of the root is improved if longer sequences are analyzed or if more taxa are added. We show that the gain in precision is faster with longer sequences than with more taxa. We also show that the algorithm of the software package PATHd8 may give biased estimates if the global molecular clock is violated. A change of the algorithm to obtain unbiased estimates is therefore suggested. The last paper deals with non-informative priors when using the Bayesian approach in phylogenetics. The term is not uniquely defined in the literature. We adopt the idea of data translated likelihoods and derive the so called Jeffreys' prior for branch lengths using Jukes Cantor model of evolution

Improving Divergence Time Estimation in Phylogenetics: More Taxa vs. Longer Sequences

Maximum Likelihood (ML) is used as a standard method for estimating divergence times in phylogenetic trees. The method is consistent and hence the precision can be improved by analyzing longer sequences. In this paper we show that the precision can be improved also by including more taxa to the existing tree. It is a theoretical study, complemented with simulations, showing that the gain in precision is faster with increasing sequence length than with increasing number of taxa.We further compare the results of estimating divergence times using Maximum Likelihood with the much faster and less complex estimation method of Mean Path Length (MPL), which works with the evolution model of Jukes-Cantor (1969). It is shown that MPL is as good as ML in estimating divergence times of nodes that are located near the root in the tree, but ML is better in estimating the divergence times of nodes lower down.

Symptoms and ECG changes precede sudden cardiac death in hypertrophic cardiomyopathy : A nationwide study among the young in Sweden

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a major cause of sudden cardiac death (SCD) in the young. We aimed to characterize detailed family history, symptoms, hospital utilization and ECG changes before SCD. METHODS: We extracted all cases suffering SCD with HCM from the SUDDY cohort, which includes all cases of SCD between 2000-2010 in Sweden among individuals aged 0-35 years along with their controls. We gathered data from mandatory national registries, autopsy reports, medical records, ECGs (including military conscripts), and detailed family history from an interview-based questionnaire (with relatives, post-mortem). RESULTS: Thirty-eight cases (7 female), mean age 22 years, with HCM were identified. Among these, 71% presented with possible cardiac symptoms (chest pain [26%], syncope [22%], palpitations [37%]), before death; 69% received medical care (vs 21% in controls) within 180 days before death. The majority (68%) died during recreational activity (n = 14) or exercise/competitive sports (n = 12). Fifteen (39%) had a known cardiac disorder prior to death, with HCM being diagnosed pre-mortem in nine cases. 58% presented with abnormal ECG recordings pre-mortem, and 50% had a positive family history (1st-3rd generation) for heart disease. CONCLUSION: In this comprehensive, nationwide study of SCD due to HCM, 87% (33/38) of cases had one or more abnormality prior to death, including cardiac symptoms, a positive family history, known cardiac disease or ECG abnormalities. They sought medical care prior death, to a larger extent than controls. These findings suggest that cardiac screening should be expanded beyond competitive athletes to aid SCD prevention in the young population with HCM

Optimized diagnosis-based comorbidity measures for all-cause mortality prediction in a national population-based ICU population

Background: We aimed to optimize prediction of long-term all-cause mortality of intensive care unit (ICU) patients, using quantitative register-based comorbidity information assessed from hospital discharge diagnoses prior to intensive care treatment. Material and methods: Adult ICU admissions during 2006 to 2012 in the Swedish intensive care register were followed for at least 4 years. The performance of quantitative comorbidity measures based on the 5-year history of number of hospital admissions, length of stay, and time since latest admission in 36 comorbidity categories was compared in time-to-event analyses with the Charlson comorbidity index (CCI) and the Simplified Acute Physiology Score (SAPS3). Results: During a 7-year period, there were 230,056 ICU admissions and 62,225 deaths among 188,965 unique individuals. The time interval from the most recent hospital stays and total length of stay within each comorbidity category optimized mortality prediction and provided clear separation of risk categories also within strata of age and CCI, with hazard ratios (HRs) comparing lowest to highest quartile ranging from 1.17 (95% CI: 0.52-2.64) to 6.41 (95% CI: 5.19-7.92). Risk separation was also observed within SAPS deciles with HR ranging from 1.07 (95% CI: 0.83-1.38) to 3.58 (95% CI: 2.12-6.03). Conclusion: Baseline comorbidity measures that included the time interval from the most recent hospital stay in 36 different comorbidity categories substantially improved long-term mortality prediction after ICU admission compared to the Charlson index and the SAPS score. Trial registration ClinicalTrials.gov ID NCT04109001, date of registration 2019-09-26 retrospectively

Low real-world early stent thrombosis rates in ST-elevation myocardial infarction patients and the use of bivalirudin, heparin alone or glycoprotein IIb/IIIa inhibitor treatment : A nationwide Swedish registry report

Background In recent studies of primary percutaneous coronary intervention (PCI), bivalirudin compared with heparin has been associated with increased risk of stent thrombosis (ST). Our aim was to describe incidence and outcome of definite, early ST in a large contemporary primary PCI population divided in antithrombotic therapy subgroups. Methods and Results A prospective, observational cohort study of all 31,258 ST-elevation myocardial infarction patients who received a stent in Sweden from January 2007 to July 2014 in the SWEDEHEART registry was conducted. Patients were divided into 3 groups: bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treated. Primary outcome measure was incidence of definite early ST (within 30 days of PCI). Secondary outcomes included all-cause mortality. Incidence of early ST was low, regardless of bivalirudin, heparin alone, or glycoprotein IIb/IIIa inhibitor treatment (0.84%, 0.94%, and 0.83%, respectively). All-cause mortality at 1 year was 20.7% for all ST patients (n = 265), compared with 9.1% in those without ST (n = 31,286;