Estimation of genetic parameters using molecular markers and EM-algorithms

In this paper we present a new method for estimating genetic parameters of an F2-generation model. Using an iterative algorithm we derive explicit expressions for the Maximum Likelihood estimates of the additive and dominance effects. Finally we calculate the variance covariance matrix of our Maximum Likelihood estimates, which enables us to determine a confidence interval for the location of a quantitative trait locus

Statistical Analysis of Spatial and Temporal Dynamics of a Bacterial Layer in an Aquatic Ecosystem

Do active vertical mass movements occur within a population of phototropic bacteria in the meromictic Lake Cadagno? An experiment was conducted in vivo to record vertical profiles of the parameters turbidity and temperature in a spatial resolution of 30cm repeatedly over time. After eliminating the temporal dependencies within both the space-time data of turbidity measurements and temperatures, the respective spatial correlation structure can be estimated. Spatial prediction (Kriging) then offers a tool to enhance the observed spatial resolution of both processes. By means of the (temporally repeated) turbidity profiles the vertical position of the bacterial layer can be estimated at each time point. Obviously its vertical displacements in course of the observational time occur not only due to active bacterial swimming; additionally the bacteria are dragged along passively by internal waves in the lake. Eliminating this latter disturbing effect the estimated temperature (instead of depth) at the bounds of the layer in course of time allows to draw conclusions on the active component of bacterial movements. Such phenomena can be found especially at the lower bound of the bacterial layer with amplitudes up to more than 30cm

Quantitative trait loci mapping in plant genetics by alpha-design experiments and molecular genetic marker systems

Research concerning the quantitative trait loci (QTL) mapping in plant genetics usually consists of two stages. The first stage is concerned with collecting data while the second one, based on the data collected, is concerned with a proper QTL study. The final inferences are strictly connected with the quality of the two approaches applied in both stages. Data to be analyzed come from an experiment dealing with offsprings obtained from a crossing system of several lines. The genotypes then are observed in some natural or quasi natural environment. The QTL studies are based on so called genotype adjusted means. In a-designs the adjusted means can be calculated in many ways, which will be presented in this paper. We also give an EM-algorithm for the estimation of genetic parameters and comment on recent biometrical research in molecular plant genetics. Finally we mention some activities in the new field of bioinformatics

A family of Type VI secretion system effector proteins that form ion-selective pores

This work was supported by the Wellcome Trust (104556/Z/14/Z, Senior Fellowship in Basic Biomedical Science to S.J.C.; 097818/Z/11/B and 109118/Z/15/Z, PhD studentships to University of Dundee), the MRC (MR/K000111X/1, New Investigator Research Grant to S.J.C.) and the Royal Society of Edinburgh (Biomedical Personal Research Fellowship to S.J.P.). We thank Roland Freudl for the gift of anti-OmpA antibody; Adam Ostrowski for construction of strains AO07 and AO08; Gal Horesh, Amy Dorward and Gavin Robertson for expert assistance; the Flow Cytometry and Cell Sorting Facility at the University of Dundee; and the Dundee Imaging Facility (supported by Wellcome Trust [097945/B/11/Z] and MRC [MR/K015869/1]) awards).Type VI secretion systems (T6SSs) are nanomachines widely used by bacteria to deliver toxic effector proteins directly into neighbouring cells. However, the modes of action of many effectors remain unknown. Here we report that Ssp6, an anti-bacterial effector delivered by a T6SS of the opportunistic pathogen Serratia marcescens, is a toxin that forms ion-selective pores. Ssp6 inhibits bacterial growth by causing depolarisation of the inner membrane in intoxicated cells, together with increased outer membrane permeability. Reconstruction of Ssp6 activity in vitro demonstrates that it forms cation-selective pores. A survey of bacterial genomes reveals that genes encoding Ssp6-like effectors are widespread in Enterobacteriaceae and often linked with T6SS genes. We conclude that Ssp6 and similar proteins represent a new family of T6SS-delivered anti-bacterial effectors.Publisher PDFPeer reviewe

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Abstract: Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P < 4 × 10−10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P < 5 × 10−10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis