Interactions between Glucocorticoid Treatment and Cis-Regulatory Polymorphisms Contribute to Cellular Response Phenotypes

Glucocorticoids (GCs) mediate physiological responses to environmental stress and are commonly used as pharmaceuticals. GCs act primarily through the GC receptor (GR, a transcription factor). Despite their clear biomedical importance, little is known about the genetic architecture of variation in GC response. Here we provide an initial assessment of variability in the cellular response to GC treatment by profiling gene expression and protein secretion in 114 EBV-transformed B lymphocytes of African and European ancestry. We found that genetic variation affects the response of nearby genes and exhibits distinctive patterns of genotype-treatment interactions, with genotypic effects evident in either only GC-treated or only control-treated conditions. Using a novel statistical framework, we identified interactions that influence the expression of 26 genes known to play central roles in GC-related pathways (e.g. NQO1, AIRE, and SGK1) and that influence the secretion of IL6

Genomic-Assisted Enhancement in Stress Tolerance for Productivity Improvement in Sorghum

Sorghum [Sorghum bicolor (L.) Moench], the fifth most important cereal crop in the world after wheat, rice, maize, and barley, is a multipurpose crop widely grown for food, feed, fodder, forage, and fuel, vital to the food security of many of the world’s poorest people living in fragile agroecological zones. Globally, sorghum is grown on ~42 million hectares area in ~100 countries of Africa, Asia, Oceania, and the Americas. Sorghum grain is used mostly as food (~55%), in the form of flat breads and porridges in Asia and Africa, and as feed (~33%) in the Americas. Stover of sorghum is an increasingly important source of dry season fodder for livestock, especially in South Asia. In India, area under sorghum cultivation has been drastically come down to less than one third in the last six decades but with a limited reduction in total production suggesting the high-yield potential of this crop. Sorghum productivity is far lower compared to its genetic potential owing to a limited exploitation of genetic and genomic resources developed in the recent past. Sorghum production is challenged by various abiotic and biotic stresses leading to a significant reduction in yield. Advances in modern genetics and genomics resources and tools could potentially help to further strengthen sorghum production by accelerating the rate of genetic gains and expediting the breeding cycle to develop cultivars with enhanced yield stability under stress. This chapter reviews the advances made in generating the genetic and genomics resources in sorghum and their interventions in improving the yield stability under abiotic and biotic stresses to improve the productivity of this climate-smart cereal

Genomic atlas of the human plasma proteome

Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as well as with disease-associated loci, and find evidence that protein biomarkers have causal roles in disease using Mendelian randomization analysis. By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development