Genome‐wide association studies (GWAS) have developed into a powerful and ubiquitous tool for the investigation of complex traits. In large part, this was fueled by advances in genomic technology, enabling us to examine genome‐wide genetic variants across diverse genetic materials. The development of the mixed model framework for GWAS dramatically reduced the number of false positives compared with naïve methods. Building on this foundation, many methods have since been developed to increase computational speed or improve statistical power in GWAS. These methods have allowed the detection of genomic variants associated with either traditional agronomic phenotypes or biochemical and molecular phenotypes. In turn, these associations enable applications in gene cloning and in accelerated crop breeding through marker assisted selection or genetic engineering. Current topics of investigation include rare‐variant analysis, synthetic associations, optimizing the choice of GWAS model, and utilizing GWAS results to advance knowledge of biological processes. Ongoing research in these areas will facilitate further advances in GWAS methods and their applications.
Identifying mechanisms and pathways involved in gene-environment interplay and phenotypic plasticity is a long-standing challenge. It is highly desirable to establish an integrated framework with an environmental dimension for complex trait dissection and prediction. A critical step is to identify an environmental index that is both biologically relevant and estimable for new environments. With extensive field-observed complex traits, environmental profiles, and genome-wide single nucleotide polymorphisms for three major crops (maize, wheat, and oat), we demonstrated that identifying such an environmental index (i.e., a combination of environmental parameter and growth window) enables genome-wide association studies and genomic selection of complex traits to be conducted with an explicit environmental dimension. Interestingly, genes identified for two reaction-norm parameters (i.e., intercept and slope) derived from flowering time values along the environmental index were less colocalized for a diverse maize panel than for wheat and oat breeding panels, agreeing with the different diversity levels and genetic constitutions of the panels. In addition, we showcased the usefulness of this framework for systematically forecasting the performance of diverse germplasm panels in new environments. This general framework and the companion CERIS-JGRA analytical package should facilitate biologically informed dissection of complex traits, enhanced performance prediction in breeding for future climates, and coordinated efforts to enrich our understanding of mechanisms underlying phenotypic variation.
Tocochromanols (tocopherols and tocotrienols, collectively vitamin E) are lipid-soluble antioxidants important for both plant fitness and human health. The main dietary sources of vitamin E are seed oils that often accumulate high levels of tocopherol isoforms with lower vitamin E activity. The tocochromanol biosynthetic pathway is conserved across plant species but an integrated view of the genes and mechanisms underlying natural variation of tocochromanol levels in seed of most cereal crops remains limited. To address this issue, we utilized the high mapping resolution of the maize Ames panel of ∼1,500 inbred lines scored with 12.2 million single-nucleotide polymorphisms to generate metabolomic (mature grain tocochromanols) and transcriptomic (developing grain) data sets for genetic mapping. By combining results from genome- and transcriptome-wide association studies, we identified a total of 13 candidate causal gene loci, including five that had not been previously associated with maize grain tocochromanols: four biosynthetic genes (arodeH2 paralog, dxs1, vte5, and vte7) and a plastid S-adenosyl methionine transporter (samt1). Expression quantitative trait locus (eQTL) mapping of these 13 gene loci revealed that they are predominantly regulated by cis-eQTL. Through a joint statistical analysis, we implicated cis-acting variants as responsible for co-localized eQTL and GWAS association signals. Our multi-omics approach provided increased statistical power and mapping resolution to enable a detailed characterization of the genetic and regulatory architecture underlying tocochromanol accumulation in maize grain and provided insights for ongoing biofortification efforts to breed and/or engineer vitamin E and antioxidant levels in maize and other cereals.
Background Disease resilience is the ability to maintain performance under pathogen exposure but is difficult to select for because breeding populations are raised under high health. Selection for resilience requires a trait that is heritable, easy to measure on healthy animals, and genetically correlated with resilience. Natural antibodies (NAb) are important parts of the innate immune system and are found to be heritable and associated with disease susceptibility in dairy cattle and poultry. Our objective was to investigate NAb and total IgG in blood of healthy, young pigs as potential indicator traits for disease resilience. Results Data were from Yorkshire x Landrace pigs, with IgG and IgM NAb (four antigens) and total IgG measured by ELISA in blood plasma collected ~ 1 week after weaning, prior to their exposure to a natural polymicrobial challenge. Heritability estimates were lower for IgG NAb (0.12 to 0.24, + 0.05) and for total IgG (0.19 + 0.05) than for IgM NAb (0.33 to 0.53, + 0.07) but maternal effects were larger for IgG NAb (0.41 to 0.52, + 0.03) and for total IgG (0.19 + 0.05) than for IgM NAb (0.00 to 0.10, + 0.04). Phenotypically, IgM NAb titers were moderately correlated with each other (average 0.60), as were IgG NAb titers (average 0.42), but correlations between IgM and IgG NAb titers were weak (average 0.09). Phenotypic correlations of total IgG were moderate with NAb IgG (average 0.46) but weak with NAb IgM (average 0.01). Estimates of genetic correlations among NAb showed similar patterns but with small SE, with estimates averaging 0.76 among IgG NAb, 0.63 among IgM NAb, 0.17 between IgG and IgM NAb, 0.64 between total IgG and IgG NAb, and 0.13 between total IgG and IgM NAb. Phenotypically, pigs that survived had slightly higher levels of NAb and total IgG than pigs that died. Genetically, higher levels of NAb tended to be associated with greater disease resilience based on lower mortality and fewer parenteral antibiotic treatments. Genome-wide association analyses for NAb titers identified several genomic regions, with several candidate genes for immune response. Conclusions Levels of NAb in blood of healthy young piglets are heritable and potential genetic indicators of resilience to polymicrobial disease.
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