DNA methylation changes play essential roles in regulating the activities of genes involved in immune responses. Understanding of variable DNA methylation linked to immune responses may contribute to identifying biologically promising epigenetic markers for pathogenesis of diseases. Here, we generated genome-wide DNA methylation and transcriptomic profiles of six pairs of polyinosinic-polycytidylic acid-treated pig peripheral blood mononuclear cell (PBMC) samples and corresponding controls using methylated DNA immunoprecipitation sequencing and RNA sequencing. Comparative methylome analyses identified 5,827 differentially methylated regions and 615 genes showing differential expression between the two groups. Integrative analyses revealed inverse associations between DNA methylation around transcriptional start site and gene expression levels. Furthermore, 70 differentially methylated and expressed genes were identified such as TNFRSF9, IDO1 and EBI3. Functional annotation revealed the enriched categories including positive regulation of immune system process and regulation of leukocyte activation. These findings demonstrated DNA methylation changes occurring in immune responses of PBMCs to poly I:C stimulation and a subset of genes potentially regulated by DNA methylation in the immune responses. The PBMC DNA methylome provides an epigenetic overview of this physiological system in response to viral infection, and we expect it to constitute a valuable resource for future epigenetic epidemiology studies in pigs.

MotivationEpistasis provides a feasible way for probing potential genetic mechanism of complex traits. However, time-consuming computation challenges successful detection of interaction in practice, especially when linear mixed model (LMM) is used to control type I error in the presence of population structure and cryptic relatedness.ResultsA rapid epistatic mixed-model association analysis (REMMA) method was developed to overcome computational limitation. This method first estimates individuals’ epistatic effects by an extended genomic best linear unbiased prediction (EG-BLUP) model with additive and epistatic kinship matrix, then pairwise interaction effects are obtained by linear retransformations of individuals’ epistatic effects. Simulation studies showed that REMMA could control type I error and increase statistical power in detecting epistatic QTNs in comparison with existing LMM-based FaST-LMM. We applied REMMA to two real datasets, a mouse dataset and the Wellcome Trust Case Control Consortium (WTCCC) data. Application to the mouse data further confirmed the performance of REMMA in controlling type I error. For the WTCCC data, we found most epistatic QTNs for type 1 diabetes (T1D) located in a major histocompatibility complex (MHC) region, from which a large interacting network with 12 hub genes (interacting with ten or more genes) was established.Availability and implementationOur REMMA method can be freely accessed at https://github.com/chaoning/REMMA.Supplementary information Supplementary data are available at Bioinformatics online.

Piglet uniformity (PU) and farrowing interval (FI) are important reproductive traits related to production and economic profits in the pig industry. However, the genetic architecture of the longitudinal trends of reproductive traits still remains elusive. Herein, we performed a genome-wide association study (GWAS) to detect potential genetic variation and candidate genes underlying the phenotypic records at different parities for PU and FI in a population of 884 Large White pigs. In total, 12 significant SNPs were detected on SSC1, 3, 4, 9, and 14, which collectively explained 1–1.79% of the phenotypic variance for PU from parity 1 to 4, and 2.58–4.11% for FI at different stages. Of these, seven SNPs were located within 16 QTL regions related to swine reproductive traits. One QTL region was associated with birth body weight (related to PU) and contained the peak SNP MARC0040730, and another was associated with plasma FSH concentration (related to FI) and contained the SNP MARC0031325. Finally, some positional candidate genes for PU and FI were identified because of their roles in prenatal skeletal muscle development, fetal energy substrate, pre-implantation, and the expression of mammary gland epithelium. Identification of novel variants and candidate genes will greatly advance our understanding of the genetic mechanisms of PU and FI, and suggest a specific opportunity for improving marker assisted selection or genomic selection in pigs.

Long noncoding RNA (lncRNA) play a critical role in mammary development and breast cancer biology. Despite their important role in the mammary gland, little is known of the roles of lncRNA in bovine lactation, particularly regarding the molecular processes underlying it. To characterize the role of lncRNA in bovine lactation, 4 samples of Holstein cow mammary gland tissue at peak and late lactation stages were examined after biopsy. We then profiled the transcriptome of the mammary gland using RNA sequencing technology. Further, functional lncRNA-mRNA coexpression pairs were constructed to infer the function of lncRNA using a generalized linear model, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. More than 1,000 putative lncRNA were identified, 117 of which were differentially expressed between peak and late lactation stages. Bovine lncRNA were shorter, with fewer exon numbers, and expressed at significantly lower levels than protein-coding genes. Seventy-two differentially expressed (DE) lncRNA were coexpressed with 340 different protein-coding genes. The KEGG pathway analysis showed that target mRNA for DE lncRNA were mainly related to lipid and glucose metabolism, including the peroxisome proliferator-activated receptors and 5′ adenosine monophosphate-activated protein kinase signaling pathways. Further bioinformatics and integrative analyses revealed that 12 DE lncRNA potentially played important roles in bovine lactation. Our findings provide a valuable resource for future bovine transcriptome studies, facilitate the understanding of bovine lactation biology, and offer functional information for cattle lactation.

BackgroundPseudo-phenotypes, such as 305-day yields, estimated breeding values or deregressed proofs, are usually used as response variables for genome-wide association studies (GWAS) of milk production traits in dairy cattle. Computational inefficiency challenges the direct use of test-day records for longitudinal GWAS with large datasets.ResultsWe propose a rapid longitudinal GWAS method that is based on a random regression model. Our method uses Eigen decomposition of the phenotypic covariance matrix to rotate the data, thereby transforming the complex mixed linear model into weighted least squares analysis. We performed a simulation study that showed that our method can control type I errors well and has higher power than a longitudinal GWAS method that does not include time-varied additive genetic effects. We also applied our method to the analysis of milk production traits in the first three parities of 6711 Chinese Holstein cows. The analysis for each trait was completed within 1 day with known variances. In total, we located 84 significant single nucleotide polymorphisms (SNPs) of which 65 were within previously reported quantitative trait loci (QTL) regions.ConclusionsOur rapid method can control type I errors in the analysis of longitudinal data and can be applied to other longitudinal traits. We detected QTL that were for the most part similar to those reported in a previous study in Chinese Holstein. Moreover, six additional SNPs for fat percentage and 13 SNPs for protein percentage were identified by our method. These additional 19 SNPs could be new candidate quantitative trait nucleotides for milk production traits in Chinese Holstein.Electronic supplementary materialThe online version of this article (10.1186/s12711-018-0383-0) contains supplementary material, which is available to authorized users.