Background: Genome wide association studies (GWAS) on residual feed intake (RFI) and its component traits including daily dry matter intake (DMI), average daily gain (ADG), and metabolic body weight (MWT) were conducted in a population of 7573 animals from multiple beef cattle breeds based on 7,853,211 imputed whole genome sequence variants. The GWAS results were used to elucidate genetic architectures of the feed efficiency related traits in beef cattle.Results: The DNA variant allele substitution effects approximated a bell-shaped distribution for all the traits while the distribution of additive genetic variances explained by single DNA variants followed a scaled inverse chi-squared distribution to a greater extent. With a threshold ofP-value < 1.00E-05, 16, 72, 88, and 116 lead DNA variants on multiple chromosomes were significantly associated with RFI, DMI, ADG, and MWT, respectively. In addition, lead DNA variants with potentially large pleiotropic effects on DMI, ADG, and MWT were found on chromosomes 6, 14 and 20. On average, missense, 3’UTR, 5’UTR, and other regulatory region variants exhibited larger allele substitution effects in comparison to other functional classes. Intergenic and intron variants captured smaller proportions of additive genetic variance per DNA variant. Instead 3’UTR and synonymous variants explained a greater amount of genetic variance per DNA variant for all the traits examined while missense, 5’UTR and other regulatory region variants accounted for relatively more additive genetic variance per sequence variant for RFI and ADG, respectively. In total, 25 to 27 enriched cellular and molecular functions were identified with lipid metabolism and carbohydrate metabolism being the most significant for the feed efficiency traits.Conclusions: RFI is controlled by many DNA variants with relatively small effects whereas DMI, ADG, and MWT are influenced by a few DNA variants with large effects and many DNA variants with small effects. Nucleotide polymorphisms in regulatory region and synonymous functional classes play a more important role per sequence variant in determining variation of the feed efficiency traits. The genetic architecture as revealed by the GWAS of the imputed 7,853,211 DNA variants will improve our understanding on the genetic control of feed efficiency traits in beef cattle.

Background: Genome wide association studies (GWAS) were conducted on 7,853,211 imputed whole genome sequence variants in a population of 3354 to 3984 animals from multiple beef cattle breeds for five carcass merit traits including hot carcass weight (HCW), average backfat thickness (AFAT), rib eye area (REA), lean meat yield (LMY) and carcass marbling score (CMAR). Based on the GWAS results, genetic architectures of the carcass merit traits in beef cattle were elucidated.Results: The distributions of DNA variant allele substitution effects approximated a bell-shaped distribution for all the traits while the distribution of additive genetic variances explained by single DNA variants conformed to a scaled inverse chi-squared distribution to a greater extent. At a threshold ofP-value < 10^–5, 51, 33, 46, 40, and 38 lead DNA variants on multiple chromosomes were significantly associated with HCW, AFAT, REA, LMY, and CMAR, respectively. In addition, lead DNA variants with potentially large pleiotropic effects on HCW, AFAT, REA, and LMY were found on chromosome 6. On average, missense variants, 3’UTR variants, 5’UTR variants, and other regulatory region variants exhibited larger allele substitution effects on the traits in comparison to other functional classes. The amounts of additive genetic variance explained per DNA variant were smaller for intergenic and intron variants on all the traits whereas synonymous variants, missense variants, 3’UTR variants, 5’UTR variants, downstream and upstream gene variants, and other regulatory region variants captured a greater amount of additive genetic variance per sequence variant for one or more carcass merit traits investigated. In total, 26 enriched cellular and molecular functions were identified with lipid metabolisms, small molecular biochemistry, and carbohydrate metabolism being the most significant for the carcass merit traits.Conclusions: The GWAS results have shown that the carcass merit traits are controlled by a few DNA variants with large effects and many DNA variants with small effects. Nucleotide polymorphisms in regulatory, synonymous, and missense functional classes have relatively larger impacts per sequence variant on the variation of carcass merit traits. The genetic architecture as revealed by the GWAS will improve our understanding on genetic controls of carcass merit traits in beef cattle.

Recently, many genome-wide association studies (GWAS) have been conducted to understand the genetic architecture of economic important traits in farm animals. Pig is widely used as a biomedical animal model for its similarity with humans in terms of organ formation and disease mechanisms. Moreover, understanding the mechanisms that underlie the development of internal organs will impact the productive potential of pigs. Our aim was to uncover new single nucleotide polymorphisms (SNPs) associated with the weight of internal organs and carcass and also potential candidate genes. We performed GWAS for the weight of heart, liver, spleen, kidney and carcass on five pig populations (White Duroc × Erhualian F2 intercross, Sutai population, Laiwu population, Erhualian population and commercial population, for a total of 2650 individuals). Genotype data was produced using the PorcineSNP60 Beadchip array. After quality control, the data was used for association tests under a general linear mixed model. Population stratification was adjusted by including a random polygenic effect based on a matrix of genotypic relationships. A meta-analysis of our GWAS datasets was conducted by summing up the Chi square values across breeds, with the degrees of freedom of the Chi square distribution equal to the effective number of breeds. Thirty-nine quantitative trait loci (QTL) located on 15 chromosomes were identified by the single-population GWAS at the suggestive level. Among these, nine QTL surpassed the 5 % genome-wide significance threshold, including four for heart weight on SSC (Sus scrofa chromosome) 2, 4, 7 and 10, two for liver weight on SSC7, two for spleen weight on SSC5 and SSC7 and one for carcass weight on SSC11. The QTL on SSC7 showed pleiotropic effects for heart, liver and spleen weights in the F2 population. In addition, two QTL were detected in several populations, including one on SSC2 for heart weight in the F2 and Sutai populations and one on SSC7 for liver weight in the F2 and Laiwu populations. The meta-analysis detected four novel QTL on SSC1, 3, 8 and 16 for carcass weight.

Long noncoding RNA (lncRNA) plays crucial roles in various biological processes of different cancers, especially acting as a competing endogenous RNA (ceRNA). However, the role of lncRNA-mediated ceRNA in Wilms tumor (WT), which is the most common malignant kidney cancer in children, remains unknown. In present study, RNA sequence profiles and clinical data of 125 patients with WT consisting of 119 tumor and 6 normal tissues from Therapeutically Applicable Research To Generate Effective Treatments database were analyzed. A total of 1833 lncRNAs, 156 microRNAs (miRNAs), and 3443 messenger RNAs (mRNAs) were identified as differentially expressed (DE) using “DESeq2” package. The lncRNA-miRNA-mRNA ceRNA regulatory network involving 748 DElncRNAs, 33 DEmiRNAs, and 189 DEmRNAs was constructed based on miRcode, Targetscan, miRTarBase, and miRDB database. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that DEmRNAs were mainly enriched in cell proliferation-related processes and tumor-related pathways, respectively, and 13 hub genes were identified by a protein–protein interaction network. Survival analysis detected 48 lncRNAs, 7 miRNAs, and 16 mRNAs to have significant impact on the overall survival of patients with WT. Additionally, we found that 6 DElncRNAs with potential prognostic value were correlated with tumor stage (DENND5B-AS1) and histologic classification (TMPO-AS1, RP3-523K23.2, RP11-598F7.3, LAMP5-AS1, and AC013275.2) of patients with WT. Our research provides a great insight into understanding the molecular mechanism underlying occurrence and progression of WT, as well as the potential to develop targeted therapies and prognostic biomarkers.

Bladder cancer (BCa) is the tenth most common tumor in humans. DNA damage repair genes (DDRGs) play important roles in many malignant tumors; thus, their functions in BCa should also be explored. We performed a comprehensive analysis of the expression profiles of DDRGs in 410 BCa tumors and 19 normal tissues from The Cancer Genome Atlas database. We identified 123 DDRGs differentially expressed between BCa tumors and normal tissues, including 95 upregulated and 28 downregulated genes. We detected 22 DDRGs associated with overall survival (OS) of patients with BCa by performing univariate Cox regression analysis. To explore the interactions between OS-associated DDRGs, we constructed a PPI network, which showed that the top six DDRGs (CDCA2, FOXM1, PBK, RRM2, ORC1, and HDAC4) with the highest scores in the PPI network might play significant roles in OS of BCa. Moreover, to investigate the latent regulatory mechanism of these OS-associated DDRGs, we analyzed the transcription factors (TFs)-DDRGs regulatory network. The core seven TFs (NCAPG, DNMT1, LMNB1, BRCA1, E2H2, CENPA, and E2F7) were shown to be critical regulators of the OS-related DDRGs. The 22 DDRGs were incorporated into a stepwise multivariable Cox analysis. Then, we built the index of risk score based on the expression of 8 DDRGs (CAD, HDAC10, JDP2, LDLR, PDGFRA, POLA2, SREBF1, and STAT1). The p-value < 0.0001 in the Kaplan–Meier survival plot and an area under the ROC curve (AUC) of 0.771 in TCGA-BLCA training dataset suggested the high specificity and sensitivity of the prognostic index. Furthermore, we validated the risk score in the internal TCGA-BLCA and an independent GSE32894 dataset, with AUC of 0.743 and 0.827, respectively. More importantly, the multivariate Cox regression and stratification analysis demonstrated that the predictor was independent of various clinical parameters, including age, tumor stage, grade, and number of positive tumor lymph nodes. In summary, a panel of 8 DNA damage repair genes associated with overall survival in bladder cancer may be a useful prognostic tool.

Obesity is a metabolic syndrome characterized by abnormal lipid deposition and energy imbalance. CD38 is a single-chain transmembrane glycoprotein widely expressed in a variety of cell types. The roles of skeletal muscle and brown fat in CD38 deficiency under HFD-induced obesity remain unknown. In this study, we established obesity model with HFD and examined the changes in metabolites with metabonomics. Our results showed that CD38 expression was increased in muscle and brown fat after HFD treatment. Moreover, the results of metabonomics showed that CD38 deficiency significantly altered the metabolites in energy metabolism, cofactor generation, and redox homeostasis. Furthermore, CD38 deficiency reduced the expressions of NADPH oxidase 2 and FASN in mRNA level. We found that the expressions of Sirt1, Sirt3, and PGC1α were upregulated in CD38-deficient muscle tissue. In brown fat, the Sirt1-3, cell death inducing DFFA-like effector A, ELOVL3, and Dio2 expressions were increased in CD38-deficient mice. Our results showed the uncoupling protein 1 expression was upregulated. And NAD⁺ supplementation increased the expression of Sirt1 and PGC1α after palmitic acid treatment. Taken together, our results demonstrated that the protection of CD38 deficiency on HFD-induced obesity was related to the inhibition of oxidative stress and increasing energy expenditure via activating NAD⁺/Sirtuins signaling pathways in muscle and brown fat.