Project description:A number of methods have been proposed to incorporate multiple scans at different intensities to reduce the quantification error and to minimize effects of saturation, but no direct comparison of their efficacy has been made. Here we used 40 technical replicates to compare individual scans at low, medium and high sensitivity with three methods for combining data from multiple scans (either 2 scan or 3 scan cases) using a variety of metrics Keywords: Multiple Scans
Project description:Plant architecture is central to yield and has been at the core of crop domestication and improvement. In cereals, inflorescence branching and leaf angle are important traits that contribute to planting density and yield potential. Several classical maize mutants show disruptions in both traits, suggesting a core regulatory network underlies pleiotropy between them. Here, we investigate regulatory modules that contribute to architectural pleiotropy between tassel branch number (TBN) and leaf angle (LA) in maize by defining transcriptional networks that function in lateral organ boundaries to promote development of these morphologically distinct organs. Using a set of nine mutants with specific developmental defects in one or both traits, we generated dynamic, context-specific gene regulatory maps that describe ligule and tassel branch development at the molecular level. Mutants introgressed into B73 and control plants were grown in environmentally controlled chambers and precisely-staged tassel primordia were hand-dissected at two stages: right before and after first primary branches initiated. Two stages capturing early development of the ligular region, including the shoot apical meristem, were also collected from mutants with LA defects. RNA-seq was performed on 140 samples and integrated into gene regulatory and co-expression networks, which were extended to include publicly available transcription factor occupancy maps for important developmental regulators, chromatin accessibility maps and natural variation to help prioritize novel genes and regulatory elements underlying diversity in LA and tassel branching phenotypes. We also used these transcriptional networks to guide multi-trait genome-wide association studies (GWAS) based on three years of field phenotyping TBN and LA traits in over 500 diverse maize lines. Various network-assisted GWAS approaches were used to identify polymorphisms in candidate genes that associate with these architecture traits and the pleiotropy between them. Our data provide novel insight into regulatory mechanisms controlling architectural pleiotropy that can be used for targeted crop improvement.
Project description:To identify novel susceptibility loci for psoriasis, we undertook a genome-wide association scan of of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls.
Project description:ene pleiotropy defines the capacity of a gene to impact multiple phenotypic characters. The Fragile X Mental Retardation 1 (FMR1) gene is a candidate for pleiotropy, as it controls protein synthesis through its product, the translational regulator FMRP. As FMR1 loss-of-function leads to neurodevelopmental defects and Fragile X Syndrome (FXS), intellectual disability and autism, FMR1 functions have been mostly studied in the brain. FMR1-deficiency could also have yet unexplored consequences in periphery and impact metabolism through translational repression in peripheral organs. We combined 1H NMR-based metabolic phenotyping and proteomics to reveal the pleiotropic metabolic effects associated with FMR1-deficiency in mouse and human. We demonstrate that Fmr1-deficiency in the mouse increases hepatic translation, improves glucose tolerance and insulin sensitivity and reduces adiposity, while enhancing -adrenergic driven lipolysis and utilization of lipid energetic substrates. Last, we provide converging evidences in FXS patients that the levels of glucose, insulin and free fatty acids are modified, suggesting that FMR1-deficiency also drives metabolic readjustments in human. As part of a larger study investigating the involvement of fmr in metabolic alteration in fmr1-KO mice, fmr1-KO mouse livers were analysed by MS.