Previous studies of horse RNA-seq were performed by mapping sequence reads to the reference genome during transcriptome analysis. However in this study, we focused on two main ideas. First, differentially expressed genes (DEGs) were identified by de novo–based analysis (DBA) in RNA-seq data from six Thoroughbreds before and after exercise, here-after referred to as “de novo unique differentially expressed genes” (DUDEG). Second, by integrating both conventional DEGs and genes identified as being selected for during domestication of Thoroughbred and Jeju pony from whole genome re-sequencing (WGS) data, we give a new concept to the definition of DEG. We identified 1, 034 and 567 DUDEGs in skeletal muscle and blood, respectively. DUDEGs in skeletal muscle were significantly related to exercise-induced stress biological process gene ontology (BP-GO) terms: ‘immune system process’; ‘response to stimulus’; and, ‘death’ and a KEGG pathways: ‘JAK-STAT signaling pathway’; ‘MAPK signaling pathway’; ‘regulation of actin cytoskeleton’; and, ‘p53 signaling pathway’. In addition, we found TIMELESS, EIF4A3 and ZNF592 in blood and CHMP4C and FOXO3 in skeletal muscle, to be in common between DUDEGs and selected genes identified by evolutionary statistics such as FST and Cross Population Extended Haplotype Homozygosity (XP-EHH). Moreover, in Thoroughbreds, three out of five genes (CHMP4C, EIF4A3 and FOXO3) related to exercise response showed relatively low nucleotide diversity compared to the Jeju pony. DUDEGs are not only conceptually new DEGs that cannot be attained from reference-based analysis (RBA) but also supports previous RBA results related to exercise in Thoroughbred. In summary, three exercise related genes which were selected for during domestication in the evolutionary history of Thoroughbred were identified as conceptually new DEGs in this study.

BackgroundDue to the lack of statistical power and confounding effects of population structure in human population data, genotype-environment interaction studies have not yielded promising results and have provided only limited knowledge for exploring how genotype and environmental factors interact to in their influence onto risk.ResultsWe analyzed 49 human quantitative traits in 7, 170 unrelated Korean individuals on 326, 262 autosomal single nucleotide polymorphisms (SNPs) collected from the KARE (Korean Association Resource) project, and we estimated the statistically significant proportion of variance that could be explained by genotype-area interactions in the supra-iliac skinfold thickness trait ( http://static-content.springer.com/image/art%3A10.1186%2F1471-2156-15-18/MediaObjects/12863_2013_1203_IEq1_HTML.gif  = 0.269 and P = 0.00032), which is related to abdominal obesity. Data suggested that the genotypes could have different effects on the phenotype (supra-iliac skinfold thickness) in different environmental settings (rural vs. urban areas). We then defined the genotype groups of individuals with similar genetic profiles based on the additive genetic relationships among individuals using SNPs. We observed the norms of reaction, and the differential phenotypic response of a genotype to a change in environmental exposure. Interestingly, we also found that the gene clusters responsible for cell-cell and cell-extracellular matrix interactions were enriched significantly for genotype-area interaction.ConclusionsThis significant heritability estimate of genotype-environment interactions will lead to conceptual advances in our understanding of the mechanisms underlying genotype-environment interactions, and could be ultimately applied to personalized preventative treatments based on environmental exposures.