Genotyping errors in a calibrated DNA register: implications for identification of individuals

<p>Abstract</p> <p>Background</p> <p>The use of DNA methods for the identification and management of natural resources is gaining importance. In the future, it is likely that DNA registers will play an increasing role in this development. Microsatellite markers have been the primary tool in ecological, medical and forensic genetics for the past two decades. However, these markers are characterized by genotyping errors, and display challenges with calibration between laboratories and genotyping platforms. The Norwegian minke whale DNA register (NMDR) contains individual genetic profiles at ten microsatellite loci for 6737 individuals captured in the period 1997-2008. These analyses have been conducted in four separate laboratories for nearly a decade, and offer a unique opportunity to examine genotyping errors and their consequences in an individual based DNA register. We re-genotyped 240 samples, and, for the first time, applied a mixed regression model to look at potentially confounding effects on genotyping errors.</p> <p>Results</p> <p>The average genotyping error rate for the whole dataset was 0.013 per locus and 0.008 per allele. Errors were, however, not evenly distributed. A decreasing trend across time was apparent, along with a strong within-sample correlation, suggesting that error rates heavily depend on sample quality. In addition, some loci were more error prone than others. False allele size constituted 18 of 31 observed errors, and the remaining errors were ten false homozygotes (i.e., the <it>true </it>genotype was a heterozygote) and three false heterozygotes (i.e., the <it>true </it>genotype was a homozygote).</p> <p>Conclusions</p> <p>To our knowledge, this study represents the first investigation of genotyping error rates in a wildlife DNA register, and the first application of mixed models to examine multiple effects of different factors influencing the genotyping quality. It was demonstrated that DNA registers accumulating data over time have the ability to maintain calibration and genotyping consistency, despite analyses being conducted on different genotyping platforms and in different laboratories. Although errors were detected, it is demonstrated that if the re-genotyping of individual samples is possible, these will have a minimal effect on the database's primary purpose, i.e., to perform individual identification.</p

The heritability of BMI varies across the range of BMI-a heritability curve analysis in a twin cohort

Background The heritability of traits such as body mass index (BMI), a measure of obesity, is generally estimated using family and twin studies, and increasingly by molecular genetic approaches. These studies generally assume that genetic effects are uniform across all trait values, yet there is emerging evidence that this may not always be the case. Method/Subjects This paper analyzes twin data using a recently developed measure of heritability called the heritability curve. Under the assumption that trait values in twin pairs are governed by a flexible Gaussian mixture distribution, heritability curves may vary across trait values. The data consist of repeated measures of BMI on 1506 monozygotic (MZ) and 2843 like-sexed dizygotic (DZ) adult twin pairs, gathered from multiple surveys in older Finnish Twin Cohorts. Results The heritability curve and BMI value-specific MZ and DZ pairwise correlations were estimated, and these varied across the range of BMI. MZ correlations were highest at BMI values from 21 to 24, with a stronger decrease for women than for men at higher values. Models with additive and dominance effects fit best at low and high BMI values, while models with additive genetic and common environmental effects fit best in the normal range of BMI. Conclusions We demonstrate that twin and molecular genetic studies need to consider how genetic effects vary across trait values. Such variation may reconcile findings of traits with high heritability and major differences in mean values between countries or over time.Peer reviewe

Исследование тепловых характеристик в виброаппарате - утилизаторе отработавшего топлива АЗС

Purpose: Self-management is crucial for effective COPD management. This study aimed at identifying associations between self-management and sociodemographic characteristics, clinical characteristics, and symptom burden in people with COPD.Patients and methods: In this cross-sectional study with 225 participants diagnosed with COPD grades II&ndash;IV, multiple linear regression analysis was conducted, using sociodemographic and clinical characteristics and symptom burden (COPD Assessment Test) as the independent variables and the eight self-management domains of the Health Education Impact Questionnaire (heiQ) as the outcome variables.Results: Higher symptom burden was significantly associated with worse scores in all self-management domains (p&lt;0.003), except for self-monitoring and insight (p=0.012). Higher disease severity (p=0.004) and numbers of comorbidities (p&lt;0.001) were associated with more emotional distress, and women scored higher than men on positive and active engagement in life (p=0.001). Higher score in pack-years smoking was associated with lower score in health-directed activities (p=0.006) and self-monitoring and insight (p&lt;0.001), and participation in organized physical training was associated with higher score in health-directed activities (p&lt;0.001). The final models explained 3.7%&ndash;31.7% of variance (adjusted R2) across the eight heiQ scales.Conclusion: A notable finding of this study was that higher symptom burden was associated with worse scores in all self-management domains, except for self-monitoring and insight. In addition, sex, disease severity, comorbidity, pack-years smoking, and participation in organized physical training were associated with one or two self-management domains. The study contributes to improved understanding of self-management in COPD. However, the explained variance levels indicate that more research needs to be done to uncover what else explains self-management domains in COPD.<br /

Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity

<p>Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54 μg/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (–OH and –COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.</p

Strategies for fitting nonlinear ecological models in R, AD Model Builder, and BUGS

Summary: 1. Ecologists often use nonlinear fitting techniques to estimate the parameters of complex ecological models, with attendant frustration. This paper compares three open-source model fitting tools and discusses general strategies for defining and fitting models. 2. R is convenient and (relatively) easy to learn, AD Model Builder is fast and robust but comes with a steep learning curve, while BUGS provides the greatest flexibility at the price of speed. 3. Our model-fitting suggestions range from general cultural advice (where possible, use the tools and models that are most common in your subfield) to specific suggestions about how to change the mathematical description of models to make them more amenable to parameter estimation. 4. A companion web site (https://groups.nceas.ucsb.edu/nonlinear-modeling/projects) presents detailed examples of application of the three tools to a variety of typical ecological estimation problems; each example links both to a detailed project report and to full source code and data

Artificial selection for increased dispersal results in lower fitness

Dispersal often covaries with other traits, and this covariation was shown to have a genetic basis. Here, we wanted to explore to what extent genetic constraints and correlational selection can explain patterns of covariation between dispersal and key life-history traits-lifespan and reproduction. A prediction from the fitness-associated dispersal hypothesis was that lower genetic quality is associated with higher dispersal propensity as driven by the benefits of genetic mixing. We wanted to contrast it with a prediction from a different model that individuals putting more emphasis on current rather than future reproduction disperse more, as they are expected to be more risk-prone and exploratory. However, if dispersal has inherent costs, this will also result in a negative genetic correlation between higher rates of dispersal and some aspects of performance. To explore this issue, we used the dioecious nematode Caenorhabditis remanei and selected for increased and decreased dispersal propensity for 10 generations, followed by five generations of relaxed selection. Dispersal propensity responded to selection, and females from high-dispersal lines dispersed more than females from low-dispersal lines. Females selected for increased dispersal propensity produced fewer offspring and were more likely to die from matricide, which is associated with a low physiological condition in Caenorhabditis nematodes. There was no evidence for differences in age-specific reproductive effort between high- and low-dispersal females. Rather, reproductive output of high-dispersal females was consistently reduced. We argue that our data provide support for the fitness-associated dispersal hypothesis

Beyond aggression: Androgen-receptor blockade modulates social interaction in wild meerkats

In male vertebrates, androgens are inextricably linked to reproduction, social dominance, and aggression, often at the cost of paternal investment or prosociality. Testosterone is invoked to explain rank-related reproductive differences, but its role within a status class, particularly among subordinates, is underappreciated. Recent evidence, especially for monogamous and cooperatively breeding species, suggests broader androgenic mediation of adult social interaction. We explored the actions of androgens in subordinate, male members of a cooperatively breeding species, the meerkat (Suricata suricatta). Although male meerkats show no rank-related testosterone differences, subordinate helpers rarely reproduce. We blocked androgen receptors, in the field, by treating subordinate males with the antiandrogen, flutamide. We monitored androgen concentrations (via baseline serum and time-sequential fecal sampling) and recorded behavior within their groups (via focal observation). Relative to controls, flutamide-treated animals initiated less and received more high-intensity aggression (biting, threatening, feeding competition), engaged in more prosocial behavior (social sniffing, grooming, huddling), and less frequently initiated play or assumed a ‘dominant’ role during play, revealing significant androgenic effects across a broad range of social behavior. By contrast, guarding or vigilance and measures of olfactory and vocal communication in subordinate males appeared unaffected by flutamide treatment. Thus, androgens in male meerkat helpers are aligned with the traditional trade-off between promoting reproductive and aggressive behavior at a cost to affiliation. Our findings, based on rare endocrine manipulation in wild mammals, show a more pervasive role for androgens in adult social behavior than is often recognized, with possible relevance for understanding tradeoffs in cooperative systems

ISG15 facilitates cellular antiviral response to dengue and west nile virus infection in vitro

<p>Abstract</p> <p>Background</p> <p>Dengue virus (DENV) and West Nile virus (WNV), close siblings of the <it>Flaviviridae </it>family, are the causative agents of Dengue hemorraghic shock or West Nile meningoencephalitis respectively. Vaccines against these two flaviviruses are currently unavailable. Interferon- Stimulated Gene 15 (<it>ISG15</it>), encoding an ubiquitin-like protein, is significantly induced by type I interferons or viral infections. Its roles in viral infections, however, vary with viruses, being either anti- or pro-viral. The exact roles of ISG15 in DENV and WNV infections remain unknown. In the current study, we evaluated the relevancies of ISG15 to DENV and WNV infection of a mouse macrophage cell line RAW264.7.</p> <p>Findings</p> <p>Quantitative PCR showed that mouse <it>Isg15 </it>was dramatically induced in DENV or WNV- infected RAW264.7 cells compared with non-infected cells. <it>Isg15 </it>and two other Jak-Stat related genes, <it>Socs1 </it>and <it>Socs3</it>, were silenced using siRNA mediated RNA interference. The intracellular DENV and WNV loads, as determined by quantitative PCR, were significantly higher in <it>Isg15 </it>silenced cells than control cells. The expression levels of interferon beta 1 (<it>Ifnb1</it>) were increased significantly in <it>Isg15</it>, <it>Socs1 </it>or <it>Socs3 </it>siRNA treated cells. Further investigation indicated that protein modification by ISG15, so called ISGylation, was significantly enhanced in DENV-infected cells compared to that in non-infected cells.</p> <p>Conclusions</p> <p>These findings suggest that ISG15 plays an anti-DENV/WNV function via protein ISGylation.</p

Epidemiology of acute and chronic hepatitis B virus infection in Norway, 1992-2009

<p>Abstract</p> <p>Background</p> <p>Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs), Men who have Sex with Men (MSM), immigrants and contacts of known carriers). We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures.</p> <p>Methods</p> <p>We used case based data from the national surveillance system on acute and chronic hepatitis B. The Norwegian Statistics Bureau provided population and migration data and the Norwegian Institute for Alcohol and Drug Research the estimated number of active IDUs between 2002-2007. Incidence rates (IR) and incidence rate ratios (IRR) for acute hepatitis B and notification rates (NR) and notification rate ratios (NRR) for chronic hepatitis B with 95% confidence intervals were calculated.</p> <p>Results</p> <p>The annual IR of acute hepatitis B ranged from 0.7/100,000 (1992) to 10.6/100,000 (1999). Transmission occurred mainly among IDUs (64%) or through sexual contact (24%). The risk of acquiring acute hepatitis B was highest in people aged 20-29 (IRR = 6.6 [3.3-13.3]), and in males (IRR = 2.4 [1.7-3.3]). We observed two peaks of newly reported chronic hepatitis B cases in 2003 and 2009 (NR = 17.6/100,000 and 17.4/100,000, respectively). Chronic hepatitis B was more likely to be diagnosed among immigrants than among Norwegians (NRR = 93 [71.9-120.6]), and among those 20-29 compared to those 50-59 (NRR = 5.2 [3.5-7.9]).</p> <p>Conclusions</p> <p>IDUs remain the largest risk group for acute hepatitis B. The observed peaks of chronic hepatitis B are related to increased immigration from high endemic countries and screening and vaccination of these groups is important to prevent further spread of infection. Universal screening of pregnant women should be introduced. A universal vaccination strategy should be considered, given the high cost of reaching the target populations. We recommend evaluating the surveillance system for hepatitis B as well as the effectiveness of screening and vaccinating immigrant populations.</p