CTmax in brook trout (Salvelinus fontinalis) embryos shows an acclimation response to developmental temperatures but is more variable than in later life stages

Critical thermal maximum (CT_max) is widely used to measure upper thermal tolerance in fish but is rarely examined in embryos. Upper thermal limits generally depend on an individual's thermal history, which molds plasticity. We examined how thermal acclimation affects thermal tolerance of brook trout (Salvelinus fontinalis) embryos using a novel method to assess CT_max in embryos incubated under three thermal regimes. Warm acclimation was associated with an increase in embryonic upper thermal tolerance. However, CT_max variability was markedly higher than is typical for juvenile or adult salmonids.     

On the frequency of copy number variants

MOTIVATION: Estimating the frequency distribution of copy number variants (CNVs) is an important aspect of the effort to characterize this new type of genetic variation. Currently, most studies report a strong skew toward low-frequency CNVs. In this article, our goal is to investigate the frequencies of CNVs. We employ a two-step procedure for the CNV frequency estimation process. We use family information a posteriori to select only the most reliable CNV regions, i.e. those showing high rates of Mendelian transmission. RESULTS: Our results suggest that the current skew toward low-frequency CNVs may not be representative of the true frequency distribution, but may be due, among other reasons, to the non-negligible false negative rates that characterize CNV detection methods. Moreover, false positives are also likely, as low-frequency CNVs are hard to detect with small sample sizes and technologies that are not ideally suited for their detection. Without appropriate validation methods, such as incorporation of biologically relevant information (for example, in our case, the transmission of heritable CNVs from parents to offspring), it is difficult to assess the validity of specific CNVs, and even harder to obtain reliable frequency estimates.     

Surface films as mosquito larvicides: partitioning the mode of action

Oils and other surface films used against mosquito larvae may act by flooding the tracheal system with oil, by disrupting the surface forces that allow larvae to rest at the surface, by toxicity, or by eliciting chemosensory responses. In an attempt to identify diagnostic symptoms of these modes of action we treated fourth-stage larvae of Culex pipiens L. form molestusForskål (Diptera: Culicidae: Culicinae) with agents operating in a single mode (Ondina oil for flooding with oil, nicotine for toxicity, and the detergent Triton X-100 for disruption of surface forces), in two modes (silicone oil) or in three (eucalyptus oil, citronellal, or caproic acid ethyl ester). We monitored the time course of flooding and immobilisation, used experiments to separate volatile toxicity from toxicity of the aqueous solution, and used video and The Observer software to analyse larval behaviour.Larvae that experienced tracheal flooding applied their mouthparts to the siphon (tail nibbling), often losing contact with the surface while doing so and falling to the bottom. Nicotine immobilised larvae without interfering with surface forces, and the larvae remained immobile hanging from the air-water interface for long periods. In detergent, larvae made repeated unsuccessful attempts to thrust the siphon through the surface. The behaviour-modifying chemicals caproic acid ethyl ester, eucalyptus oil and citronellal all operated in more than one mode. They all decreased the proportion of time larvae spent at the surface, whereas Ondina oil and silicone fluid increased it.Using this approach it should be possible to identify the modes of action of novel larvicidal agents. This could form a basis for rational design of larvicides giving an optimal compromise between efficacy against mosquito larvae and minimal damage to non-target organisms.     

Resequencing candidate genes implicates rare variants in asthma susceptibility

Common variation in over 100 genes has been implicated in the risk of developing asthma, but the contribution of rare variants to asthma susceptibility remains largely unexplored. We selected nine genes that showed the strongest signatures of weak purifying selection from among 53 candidate asthma-associated genes, and we sequenced the coding exons and flanking noncoding regions in 450 asthmatic cases and 515 nonasthmatic controls. We observed an overall excess of p values <0.05 (p = 0.02), and rare variants in four genes (AGT, DPP10, IKBKAP, and IL12RB1) contributed to asthma susceptibility among African Americans. Rare variants in IL12RB1 were also associated with asthma susceptibility among European Americans, despite the fact that the majority of rare variants in IL12RB1 were specific to either one of the populations. The combined evidence of association with rare noncoding variants in IL12RB1 remained significant (p = 3.7 × 10(-4)) after correcting for multiple testing. Overall, the contribution of rare variants to asthma susceptibility was predominantly due to noncoding variants in sequences flanking the exons, although nonsynonymous rare variants in DPP10 and in IL12RB1 were associated with asthma in African Americans and European Americans, respectively. This study provides evidence that rare variants contribute to asthma susceptibility. Additional studies are required for testing whether prioritizing genes for resequencing on the basis of signatures of purifying selection is an efficient means of identifying novel rare variants that contribute to complex disease.     

Genes to diseases (G2D) computational method to identify asthma candidate genes

Asthma is a complex trait for which different strategies have been used to identify its environmental and genetic predisposing factors. Here, we describe a novel methodological approach to select candidate genes for asthma genetic association studies. In this regard, the Genes to Diseases (G2D) computational tool has been used in combination with a genome-wide scan performed in a sub-sample of the Saguenay-Lac-St-Jean (SLSJ) asthmatic familial collection (n = 609) to identify candidate genes located in two suggestive loci shown to be linked with asthma (6q26) and atopy (10q26.3), and presenting differential parent-of-origin effects. This approach combined gene selection based on the G2D data mining analysis of the bibliographic and protein public databases, or according to the genes already known to be associated with the same or a similar phenotype. Ten genes (LPA, NOX3, SNX9, VIL2, VIP, ADAM8, DOCK1, FANK1, GPR123 and PTPRE) were selected for a subsequent association study performed in a large SLSJ sample (n = 1167) of individuals tested for asthma and atopy related phenotypes. Single nucleotide polymorphisms (n = 91) within the candidate genes were genotyped and analysed using a family-based association test. The results suggest a protective association to allergic asthma for PTPRE rs7081735 in the SLSJ sample (p = 0.000463; corrected p = 0.0478). This association has not been replicated in the Childhood Asthma Management Program (CAMP) cohort. Sequencing of the regions around rs7081735 revealed additional polymorphisms, but additional genotyping did not yield new associations. These results demonstrate that the G2D tool can be useful in the selection of candidate genes located in chromosomal regions linked to a complex trait.     

The IL12B gene is associated with asthma

The IL12B gene on chromosome 5q31-33 encodes the p40 subunit of interleukin 12, an immunomodulatory cytokine. To test the hypothesis that the IL12B gene contains polymorphisms associated with asthma, we genotyped six haplotype-tagging polymorphisms in the IL12B gene, both in 708 children enrolled in the Childhood Asthma Management Program (CAMP) and in their parents. Using the family-based association test (FBAT) program and its haplotype (HBAT) and phenotype (PBAT) options, we tested each polymorphism and haplotype for association with asthma and asthma-related phenotypes. We tested positive associations for replication in a case-control study comparing 177 adult moderate-to-severe asthmatics with 177 nonasthmatic controls. In whites in the CAMP cohort, the A allele of the IL12B G4237A polymorphism was undertransmitted to asthmatic children (P=.0008, recessive model), the global test for haplotypes for affection status was positive (P=.009, multiallelic chi (2)), and two polymorphisms were associated with different atopy phenotypes. In addition, we found a strong association between the IL12B_4237 and IL12B_6402 polymorphisms and an asthma-severity phenotype in whites, which we also found in the independent population of white adult asthmatics. IL12B may be an important asthma gene.     

On the replication of genetic associations: timing can be everything!

The failure of researchers to replicate genetic-association findings is most commonly attributed to insufficient statistical power, population stratification, or various forms of between-study heterogeneity or environmental influences.(1) Here, we illustrate another potential cause for nonreplications that has so far not received much attention in the literature. We illustrate that the strength of a genetic effect can vary by age, causing "age-varying associations." If not taken into account during the design and the analysis of a study, age-varying genetic associations can cause nonreplication. By using the 100K SNP scan of the Framingham Heart Study, we identified an age-varying association between a SNP in ROBO1 and obesity and hypothesized an age-gene interaction. This finding was followed up in eight independent samples comprising 13,584 individuals. The association was replicated in five of the eight studies, showing an age-dependent relationship (one-sided combined p = 3.92 x 10(-9), combined p value from pediatric cohorts = 2.21 x 10(-8), combined p value from adult cohorts = 0.00422). Furthermore, this study illustrates that it is difficult for cross-sectional study designs to detect age-varying associations. If the specifics of age- or time-varying genetic effects are not considered in the selection of both the follow-up samples and in the statistical analysis, important genetic associations may be missed.     

Moving academic conferences online: Aids and barriers to delegate participation

In‐person academic conferences are important to disseminate research and provide networking opportunities. Whether academics attend in‐person conferences is based on the cost, accessibility, and safety of the event. Therefore, in‐person conferences are less accessible to academics and stakeholders that are unable to overcome some of these factors, which then act as a barrier to equal and inclusive participation. Additionally, the carbon footprint of conference travel is increasingly becoming a factor in deciding on whether to attend a conference. Online conferences may provide opportunities to mitigate these challenges. Here, we illustrate how a learned society can move their conference online. Then, comparing data acquired from the virtual conference and previous in‐person conferences, we explore the aids and barriers influencing the decision of delegates to attend the meetings. Ultimately, moving meetings online aids delegate participation by removing concerns about travel, cost, and carbon emissions, but there remains a barrier to participation as online meetings are perceived as less effective for networking and social opportunities.