Selection of Optimal Ancestry Informative Markers for Classification and Ancestry Proportion Estimation in Pigs

Using small sets of ancestry informative markers (AIMs) constitutes a cost-effective method to accurately estimate the ancestry proportions of individuals. This study aimed to generate a small and effective number of AIMs from ∼60 K single nucleotide polymorphism (SNP) data of porcine and estimate three ancestry proportions [East China pig (ECHP), South China pig (SCHP), and European commercial pig (EUCP)] from Asian breeds and European domestic breeds. A total of 186 samples of 10 pure breeds were divided into three groups: ECHP, SCHP, and EUCP. Using these samples and a one-vs.-rest SVM classifier, we found that using only seven AIMs could completely separate the three groups. Subsequently, we utilized supervised ADMIXTURE to calculate ancestry proportions and found that the 129 AIMs performed well on ancestry estimates when pseudo admixed individuals were used. Furthermore, another 969 samples of 61 populations were applied to evaluate the performance of the 129 AIMs. We also observed that the 129 AIMs were highly correlated with estimates using ∼60 K SNP data for three ancestry components: ECHP (Pearson correlation coefficient (r) = 0.94), SCHP (r = 0.94), and EUCP (r = 0.99). Our results provided an example of using a small number of pig AIMs for classifications and estimating ancestry proportions with high accuracy and in a cost-effective manner

Toll-Like Receptor 9 Is Required for Opioid-Induced Microglia Apoptosis

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. However, the underlying mechanism by which microglia in response to opioids remains largely unknown. Here we show that morphine induces the expression of Toll-like receptor 9 (TLR9), a key mediator of innate immunity and inflammation. Interestingly, TLR9 deficiency significantly inhibited morphine-induced apoptosis in microglia. Similar results were obtained when endogenous TLR9 expression was suppressed by the TLR9 inhibitor CpGODN. Inhibition of p38 MAPK by its specific inhibitor SB203580 attenuated morphine-induced microglia apoptosis in wild type microglia. Morphine caused a dramatic decrease in Bcl-2 level but increase in Bax level in wild type microglia, but not in TLR9 deficient microglia. In addition, morphine treatment failed to induce an increased levels of phosphorylated p38 MAPK and MAP kinase kinase 3/6 (MKK3/6), the upstream MAPK kinase of p38 MAPK, in either TLR9 deficient or µ-opioid receptor (µOR) deficient primary microglia, suggesting an involvement of MAPK and µOR in morphine-mediated TLR9 signaling. Moreover, morphine-induced TLR9 expression and microglia apoptosis appears to require μOR. Collectively, these results reveal that opioids prime microglia to undergo apoptosis through TLR9 and µOR as well. Taken together, our data suggest that inhibition of TLR9 and/or blockage of µOR is capable of preventing opioid-induced brain damage

Genome-Wide Association Study of Age at First Calving in U.S. Holstein Cows

A genome-wide association study (GWAS) of age at first calving (AFC) using 813,114 first lactation Holstein cows and 75,524 SNPs identified 2063 additive effects and 29 dominance effects with p-values −8. Three chromosomes had highly significant additive effects in the regions of 7.86–8.12 Mb of Chr15, 27.07–27.48 Mb and 31.25–32.11 Mb of Chr19, and 26.92–32.60 Mb of Chr23. Two of the genes in those regions were reproductive hormone genes with known biological functions that should be relevant to AFC, the sex hormone binding globulin (SHBG) gene, and the progesterone receptor (PGR) gene. The most significant dominance effects were near or in EIF4B and AAAS of Chr05 and AFF1 and KLHL8 of Chr06. All dominance effects were positive overdominance effects where the heterozygous genotype had an advantage, and the homozygous recessive genotype of each SNP had a very negative dominance value. Results from this study provided new evidence and understanding about the genetic variants and genome regions affecting AFC in U.S. Holstein cows

A Large-Scale Genome-Wide Association Study of Epistasis Effects of Production Traits and Daughter Pregnancy Rate in U.S. Holstein Cattle

Epistasis is widely considered important, but epistasis studies lag those of SNP effects. Genome-wide association study (GWAS) using 76,109 SNPs and 294,079 first-lactation Holstein cows was conducted for testing pairwise epistasis effects of five production traits and three fertility traits: milk yield (MY), fat yield (FY), protein yield (PY), fat percentage (FPC), protein percentage (PPC), and daughter pregnancy rate (DPR). Among the top 50,000 pairwise epistasis effects of each trait, the five production traits had large chromosome regions with intra-chromosome epistasis. The percentage of inter-chromosome epistasis effects was 1.9% for FPC, 1.6% for PPC, 10.6% for MY, 29.9% for FY, 39.3% for PY, and 84.2% for DPR. Of the 50,000 epistasis effects, the number of significant effects with log10(1/p) ≥ 12 was 50,000 for FPC and PPC, and 10,508, 4763, 4637 and 1 for MY, FY, PY and DPR, respectively, and A × A effects were the most frequent epistasis effects for all traits. Majority of the inter-chromosome epistasis effects of FPC across all chromosomes involved a Chr14 region containing DGAT1, indicating a potential regulatory role of this Chr14 region affecting all chromosomes for FPC. The epistasis results provided new understanding about the genetic mechanism underlying quantitative traits in Holstein cattle

Genome-Wide Identification of Specific Genetic Loci Common to Sheep and Goat

Sheep and goat may become carriers of some zoonotic diseases. They are important livestock and experimental model animals for human beings. The fast and accurate identification of genetic materials originating from sheep and goat can prevent and inhibit the spread of some zoonotic diseases, monitor market product quality, and maintain the stability of animal husbandry and food industries. This study proposed a methodology for identifying sheep and goat common specific sites from a genome-wide perspective. A total of 150 specific sites were selected from three data sources, including the coding sequences of single copy genes from nine species (sheep, goat, cow, pig, dog, horse, human, mouse, and chicken), the dbSNPs for these species, and human 100-way alignment data. These 150 sites exhibited low intraspecific heterogeneity in the resequencing data of 1450 samples from five species (sheep, goat, cow, pig, and chicken) and high interspecific divergence in the human 100-way alignment data after quality control. The results were proven to be reliable at the data level. Using the process proposed in this study, specific sites of other species can be screened, and genome-level species identification can be performed using the screened sites

A comprehensive analysis of immunoglobulin heavy chain genes in the Bactrian camel (Camelus bactrianus)

Heavy chain only antibodies (HCAbs) represent a rare type of antibody that is devoid of light chains and the CH1 domain that have been reported in cartilaginous fish and camelids. By analyzing transcript data and genome sequences, we conducted a comprehensive analysis of Bactrian camel immunoglobulin heavy chain genes. Based on the transcript data, one μ gene, five γ genes, one α gene and one ε gene were found. Additionally, the variable region of HCAbs (VHH) and the conventional antibodies (VH) sequences associated with the γ3, γ1a/b and μ genes were amplified. Based on these genome sequences, seven DH, six JH, μ, γ2a, γ2c, α, and ε genes and a portion of a γ3 gene were observed. Different Kozak sequences within different VH families were found in our analysis, and the variability index differed between the VHH3 and VH3 families. Phylogenetic analysis of the constant regions of the camelid immunoglobulin genes indicates that these genes appeared before the evolutionary divergence of Bactrian camels and dromedaries

Modelling porcine NAFLD by deletion of leptin and defining the role of AMPK in hepatic fibrosis

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic hepatic disease and results in non-alcoholic steatohepatitis (NASH), which progresses to fibrosis and cirrhosis. Although the Leptin deficient rodent models are widely used in study of metabolic syndrome and obesity, they fail to develop liver injuries as in patients. Methods Due to the high similarity with humans, we generated Leptin-deficient (Leptin −/− ) pigs to investigate the mechanisms and clinical trials of obesity and NAFLD caused by Leptin. Results The Leptin −/− pigs showed increased body fat and significant insulin resistance at the age of 12 months. Moreover, Leptin −/− pig developed fatty liver, non-alcoholic steatohepatitis and hepatic fibrosis with age. Absence of Leptin in pig reduced the phosphorylation of JAK2-STAT3 and AMPK. The inactivation of JAK2-STAT3 and AMPK enhanced fatty acid β-oxidation and leaded to mitochondrial autophagy respectively, and both contributed to increased oxidative stress in liver cells. In contrast with Leptin −/− pig, although Leptin deletion in rat liver inhibited JAK2-STAT3 phosphorylation, the activation of AMPK pathway might prevent liver injury. Therefore, β-oxidation, mitochondrial autophagy and hepatic fibrosis did not occurred in Leptin −/− rat livers. Conclusions The Leptin-deficient pigs presents an ideal model to illustrate the full spectrum of human NAFLD. The activity of AMPK signaling pathway suggests a potential target to develop new strategy for the diagnosis and treatment of NAFLD