Discovery of Rare Variants via Sequencing: Implications for the Design of Complex Trait Association Studies

There is strong evidence that rare variants are involved in complex disease etiology. The first step in implicating rare variants in disease etiology is their identification through sequencing in both randomly ascertained samples (e.g., the 1,000 Genomes Project) and samples ascertained according to disease status. We investigated to what extent rare variants will be observed across the genome and in candidate genes in randomly ascertained samples, the magnitude of variant enrichment in diseased individuals, and biases that can occur due to how variants are discovered. Although sequencing cases can enrich for casual variants, when a gene or genes are not involved in disease etiology, limiting variant discovery to cases can lead to association studies with dramatically inflated false positive rates

Physiological and ecological implications of ocean deoxygenation for vision in marine organisms

Climate change has induced ocean deoxygenation and exacerbated eutrophication-driven hypoxia in recent decades, affecting the physiology, behaviour and ecology of marine organisms. The high oxygen demand of visual tissues and the known inhibitory effects of hypoxia on human vision raise the questions if and how ocean deoxygenation alters vision in marine organisms. This is particularly important given the rapid loss of oxygen and strong vertical gradients in oxygen concentration in many areas of the ocean. This review evaluates the potential effects of low oxygen (hypoxia) on visual function in marine animals and their implications for marine biota under current and future ocean deoxygenation based on evidence from terrestrial and a few marine organisms. Evolutionary history shows radiation of eye designs during a period of increasing ocean oxygenation. Physiological effects of hypoxia on photoreceptor function and light sensitivity, in combination with morphological changes that may occur throughout ontogeny, have the potential to alter visual behaviour and, subsequently, the ecology of marine organisms, particularly for fish, cephalopods and arthropods with 'fast' vision. Visual responses to hypoxia, including greater light requirements, offer an alternative hypothesis for observed habitat compression and shoaling vertical distributions in visual marine species subject to ocean deoxygenation, which merits further investigation.This article is part of the themed issue 'Ocean ventilation and deoxygenation in a warming world'

Screening for HIV, hepatitis B and syphilis on dried blood spots: A promising method to better reach hidden high-risk populations with self-collected sampling

Many people at high risk for sexually transmitted infections (STIs), e.g., men who have sex with men (MSM), are not optimally reached by current sexual health care systems with testing. To facilitate testing by home-based sampling or sampling in outreach setting we evaluated dried blood spots (DBS), a method for self-collected blood sampling for serological screening of HIV, hepatitis B (HBV) and syphilis. The aims of this study were to assess the acceptability and feasibility of self-collected DBS and to compare the test results for screening of HIV, HBV and syphilis from DBS with blood drawn by venous puncture.DBS were collected from men who have sex with men (MSM), visiting the STI clinic of the public health service South Limburg (n = 183) and HIV positive and HBV positive patients (n = 34), visiting the outpatient clinics of the Maastricht University Medical Centre in the period January 2012-April 2015. The 93 first participating MSM visiting the STI clinic were asked to fill in a questionnaire about the feasibility and acceptability about self-collection of DBS in a setting without going to a health care facility and were asked to collect the DBS themselves. Serological screening tests for HIV (HIV combi PT, Roche), HBV (HBsAg, Roche) and syphilis (Treponema pallidum Ig, Biokit 3.0) were performed on DBS and on blood drawn by venous puncture, which was routinely taken for screening.In total 217 participants were included in the study with a median age of 40 years (range between 17-80). Of MSM 84% agreed that it was clear and easy to do the finger-prick, while 53% agreed that it was clear and easy to apply the blood onto the DBS card. Also, 80% of MSM would use the bloodspot test again. In 91% (198) of DBS, sufficient material was collected to perform the three tests. No difference was observed in DBS quality between self-collected DBS and health care worker collected DBS. For HIV (n = 195 DBS-serum pairs) sensitivity and specificity were 100%. For HBV the sensitivity for HBsAg (n = 202) was 90% and specificity was 99%. For syphilis (n = 191) the sensitivity of the DBS was 93% with a specificity of 99%. Analysis of the DBS of HIV positive participants (n = 38) did show similar test performance for HBV and syphilis as in HIV negatives.DBS is an acceptable self-sampling method for MSM, as there was no difference in DBS quality in self-collected and health care worker collected DBS. Test performance, i.e., its high sensitivity (>90%) and specificity (>99%) measures show that DBS is a valid alternative for venous blood puncture. Especially when DBS is combined with home-collected sampling for Chlamydia trachomatis and Neisseria gonorrhoeae, complete STI screening can be done in outreach setting and/or home-collected sampling in MSM