326 research outputs found
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A framework for gene mapping in wheat demonstrated using the Yr7 yellow rust resistance gene
We used three approaches to map the yellow rust resistance gene Yr7 and identify associated SNPs in wheat. First, we used a traditional QTL mapping approach using a double haploid (DH) population and mapped Yr7 to a low-recombination region of chromosome 2B. To fine map the QTL, we then used an association mapping panel. Both populations were SNP array genotyped allowing alignment of QTL and genome-wide association scans based on common segregating SNPs. Analysis of the association panel spanning the QTL interval, narrowed the interval down to a single haplotype block. Finally, we used mapping-by-sequencing of resistant and susceptible DH bulks to identify a candidate gene in the interval showing high homology to a previously suggested Yr7 candidate and to populate the Yr7 interval with a higher density of polymorphisms. We highlight the power of combining mapping-by-sequencing, delivering a complete list of gene-based segregating polymorphisms in the interval with the high recombination, low LD precision of the association mapping panel. Our mapping-by-sequencing methodology is applicable to any trait and our results validate the approach in wheat, where with a near complete reference genome sequence, we are able to define a small interval containing the causative gene
Phylogeny-wide analysis of G-protein coupled receptors in social amoebas and implications for the evolution of multicellularity:[version 2; peer review: 2 approved]
G-protein coupled receptors (GPCRs) are seven-transmembrane proteins and constitute the largest group of receptors within eukaryotes. The presence of a large set of GPRCs in the unicellular Amoebozoa was surprising and is indicative of the largely undiscovered environmental sensing capabilities in this group. Evolutionary transitions from unicellular to multicellular lifestyles, like we see in social amoebas, have occurred several times independently in the Amoebozoa, and GPCRs may have been co-opted for new functions in cell-cell communication. Methods We have analysed a set of GPCRs from fully sequenced Amoebozoan genomes by Bayesian inference, compared their phylogenetic distribution and domain composition, and analysed their temporal and spatial expression patterns in five species of dictyostelids. Results We found evidence that most GPCRs are conserved deeply in the Amoebozoa and are probably performing roles in general cell functions and complex environmental sensing. All families of GPCRs (apart from the family 4 fungal pheromone receptors) are present in dictyostelids with family 5 being the largest and family 2 the one with the fewest members. For the first time, we identify the presence of family 1 rhodopsin-like GPCRs in dictyostelids. Some GPCRs have been amplified in the dictyostelids and in specific lineages thereof and through changes in expression patterns may have been repurposed for signalling in multicellular development. Discussion Our phylogenetic analysis suggests that GPCR families 1, 2 and 6 already diverged early in the Amoebozoa, whereas families 3 and 5 expanded later within the dictyostelids. The family 6 cAMP receptors that have experimentally supported roles in multicellular development in dictyostelids (
carA-carD;
tasA/B) originated at the root of all dictyostelids and only have weakly associated homologs in
Physarum polycephalum. Our analysis identified candidate GPCRs which have evolved in the dictyostelids and could have been co-opted for multicellular development
Computational investigation in the aorta of children with Turner syndrome
The aortic arch has complex flow dynamics, with locations of arterial curvature and bifurcation known to be prone to endothelial dysfunction one of the early biological markers for atherosclerotic lesions that underlie most cardiovascular disease. This is particularly relevant to conditions of obesity, which is believed to accelerate the initiation and progression of vascular changes. A computational investigation found morphological differences between the patient-specific geometries to have a strong effect on the haemodynamic environment, and low wall shear stress at areas where atherosclerotic lesions have been suggested to develop preferentially
Computational haemodynamics in Turner syndrome patient-specific aortae with PC-MRI obtained boundary conditions
Women with Turner syndrome (TS), a chromosomal condition in which a female has complete or partial absence of the second sex chromosome, present a unique group of patients, with an increased risk of cardiovascular disease. Mortality rates are three times higher in TS women compared with the general population, and life expectancy is reduced by up to 13 years –the most common cause of death being from cardiovascular disease. Congenital heart abnormalities occur in up to 50% of TS individuals, with bicuspid aortic valve, coarctation of the aorta, and thoracic aortic aneurysm being the most prevalent. Women with TS also have a greater underlying predisposition to metabolic abnormalities, such as obesity, which can exacerbate coronary artery disease, myocardial infarction, and stroke in TS adults. In this study, computational fluid dynamic (CFD)methods were used to analyse the arterial blood flow in children with Turner syndrome, who are known to present an increased risk of obesity and cardiovascular disease. Three-dimensional patient geometries were matched with patient-specific boundary conditions in the first unsteady simulation of blood flow in TS children. Morphological aortic differences between patients were found to have a strong effect on the haemodynamic environment and may be a marker for increased cardiovascular risk
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