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.
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 of P-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.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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 of P-value < 10
, 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.
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.
Celotno besedilo
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Feed efficiency is one of the key determinants of beef industry profitability and sustainability. However, the cellular and molecular background behind feed efficiency is largely unknown. This study ...combines imputed whole genome DNA variants and 31 plasma metabolites to dissect genes and biological functions/processes that are associated with residual feed intake (RFI) and its component traits including daily dry matter intake (DMI), average daily gain (ADG), and metabolic body weight (MWT) in beef cattle.
Regression analyses between feed efficiency traits and plasma metabolites in a population of 493 crossbred beef cattle identified 5 (L-valine, lysine, L-tyrosine, L-isoleucine, and L-leucine), 4 (lysine, L-lactic acid, L-tyrosine, and choline), 1 (citric acid), and 4 (L-glutamine, glycine, citric acid, and dimethyl sulfone) plasma metabolites associated with RFI, DMI, ADG, and MWT (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using 10,488,742 imputed SNPs, 40, 66, 15, and 40 unique candidate genes were identified as associated with RFI, DMI, ADG, and MWT (P-value < 1 × 10
), respectively. These candidate genes were found to be involved in some key metabolic processes including metabolism of lipids, molecular transportation, cellular function and maintenance, cell morphology and biochemistry of small molecules.
This study identified metabolites, candidate genes and enriched biological functions/processes associated with RFI and its component traits through the integrative analyses of metabolites with phenotypic traits and DNA variants. Our findings could enhance the understanding of biochemical mechanisms of feed efficiency traits and could lead to improvement of genomic prediction accuracy via incorporating metabolite data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Improvement of carcass merit traits is a priority for the beef industry. Discovering DNA variants and genes associated with variation in these traits and understanding biological functions/processes ...underlying their associations are of paramount importance for more effective genetic improvement of carcass merit traits in beef cattle. This study integrates 10,488,742 imputed whole genome DNA variants, 31 plasma metabolites, and animal phenotypes to identify genes and biological functions/processes that are associated with carcass merit traits including hot carcass weight (HCW), rib eye area (REA), average backfat thickness (AFAT), lean meat yield (LMY), and carcass marbling score (CMAR) in a population of 493 crossbred beef cattle. Regression analyses were performed to identify plasma metabolites associated with the carcass merit traits, and the results showed that 4 (3-hydroxybutyric acid, acetic acid, citric acid, and choline), 6 (creatinine, L-glutamine, succinic acid, pyruvic acid, L-lactic acid, and 3-hydroxybutyric acid), 4 (fumaric acid, methanol, D-glucose, and glycerol), 2 (L-lactic acid and creatinine), and 5 (succinic acid, fumaric acid, lysine, glycine, and choline) plasma metabolites were significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using the 10,488,742 imputed SNPs, 103, 160, 83, 43, and 109 candidate genes were identified as significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 1 × 10
), respectively. By applying functional enrichment analyses for candidate genes of each trait, 26, 24, 26, 24, and 28 significant cellular and molecular functions were predicted for HCW, REA, AFAT, LMY, and CMAR, respectively. Among the five topmost significantly enriched biological functions for carcass merit traits, molecular transport and small molecule biochemistry were two top biological functions associated with all carcass merit traits. Lipid metabolism was the most significant biological function for LMY and CMAR and it was also the second and fourth highest biological function for REA and HCW, respectively. Candidate genes and enriched biological functions identified by the integrative analyses of metabolites with phenotypic traits and DNA variants could help interpret the results of previous genome-wide association studies for carcass merit traits. Our integrative study also revealed additional potential novel genes associated with these economically important traits. Therefore, our study improves understanding of the molecular and biological functions/processes that influence carcass merit traits, which could help develop strategies to enhance genomic prediction of carcass merit traits with incorporation of metabolomic data. Similarly, this information could guide management practices, such as nutritional interventions, with the purpose of boosting specific carcass merit traits.
The genetic mechanisms controlling residual feed intake (RFI) in beef cattle are still largely unknown. Here we performed whole transcriptome analyses to identify differentially expressed (DE) genes ...and their functional roles in liver tissues between six extreme high and six extreme low RFI steers from three beef breed populations including Angus, Charolais, and Kinsella Composite (KC). On average, the next generation sequencing yielded 34 million single-end reads per sample, of which 87% were uniquely mapped to the bovine reference genome. At false discovery rate (FDR) < 0.05 and fold change (FC) > 2, 72, 41, and 175 DE genes were identified in Angus, Charolais, and KC, respectively. Most of the DE genes were breed-specific, while five genes including TP53INP1, LURAP1L, SCD, LPIN1, and ENSBTAG00000047029 were common across the three breeds, with TP53INP1, LURAP1L, SCD, and LPIN1 being downregulated in low RFI steers of all three breeds. The DE genes are mainly involved in lipid, amino acid and carbohydrate metabolism, energy production, molecular transport, small molecule biochemistry, cellular development, and cell death and survival. Furthermore, our differential gene expression results suggest reduced hepatic lipid synthesis and accumulation processes in more feed efficient beef cattle of all three studied breeds.
Bovine respiratory disease (BRD) is the most common and costly infectious disease affecting the wellbeing and productivity of beef cattle in North America. BRD is a complex disease whose development ...is dependent on environmental factors and host genetics. Due to the polymicrobial nature of BRD, our understanding of the genetic and molecular mechanisms underlying the disease is still limited. This knowledge would augment the development of better genetic/genomic selection strategies and more accurate diagnostic tools to reduce BRD prevalence. Therefore, this study aimed to utilize multi-omics data (genomics, transcriptomics, and metabolomics) analyses to study the genetic and molecular mechanisms of BRD infection. Blood samples of 143 cattle (80 BRD; 63 non-BRD animals) were collected for genotyping, RNA sequencing, and metabolite profiling. Firstly, a genome-wide association study (GWAS) was performed for BRD susceptibility using 207,038 SNPs. Two SNPs (Chr5:25858264 and BovineHD1800016801) were identified as associated (
-value <1 × 10
) with BRD susceptibility. Secondly, differential gene expression between BRD and non-BRD animals was studied. At the significance threshold used (log
FC>2, logCPM>2, and FDR<0.01), 101 differentially expressed (DE) genes were identified. These DE genes significantly (
-value <0.05) enriched several immune responses related functions such as inflammatory response. Additionally, we performed expression quantitative trait loci (eQTL) analysis and identified 420 cis-eQTLs and 144 trans-eQTLs significantly (FDR <0.05) associated with the expression of DE genes. Interestingly, eQTL results indicated the most significant SNP (Chr5:25858264) identified
GWAS was a cis-eQTL for DE gene
This analysis also demonstrated that an important SNP (rs209419196) located in the promoter region of the DE gene
significantly influenced the expression of this gene. Finally, the abundance of 31 metabolites was significantly (FDR <0.05) different between BRD and non-BRD animals, and 17 of them showed correlations with multiple DE genes, which shed light on the interactions between immune response and metabolism. This study identified associations between genome, transcriptome, metabolome, and BRD phenotype of feedlot crossbred cattle. The findings may be useful for the development of genomic selection strategies for BRD susceptibility, and for the development of new diagnostic and therapeutic tools.
The tiger pufferfish (Takifugu rubripes), also known as fugu, has recently suffered from severe C. irritans infections under aquaculture environment, yet the underlying immune mechanisms against the ...parasite remain poorly understood. In this study, we conducted a comprehensive transcriptome analysis of the gill tissue from infected and uninfected fish using PacBio long-read (one pooled sample each for seriously infected and healthy individuals, respectively) and Illumina short-read (three pools for mildly infected, seriously infected, and healthy individuals, respectively) RNA sequencing technologies. After aligning sequence data to fugu’s reference genome, 47,307 and 34,413 known full-length transcripts were identified and profiled in healthy and infected fish, respectively. Similarly, we identified and profiled 1126 and 803 novel genes that were obtained from healthy and infected fish, respectively. Interestingly, we found a decrease in the number of alternative splicing (AS) events and long non-coding RNAs (lncRNAs) after infection with C. irritans, suggesting that they may be involved in the regulation of the immune response in fugu. There were 687 and 1535 differentially expressed genes (DEGs) in moderately and heavily infected fish, respectively, compared to uninfected fish. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that immune-related DEGs in the two comparison groups were mainly enriched in cytokine-cytokine receptor interactions, ECM-receptor interactions, T-cell receptor signaling pathways, Th1 and Th2 cell differentiation, and Th17 cell differentiation pathways. Further analysis revealed that a large number of immune-related genes were downregulated in infected fish relative to uninfected ones, such as CCR7, IL7R, TNFRSF21, CD4, COL2A1, FOXP3B, and ITGA8. Our study suggests that C. irritans is potentially a highly efficient parasite that may disrupt the defense mechanisms of fugu against it. In addition, in combination of short-read RNA sequencing and previous genome-wide association analyses, we identified five key genes (NDUFB6, PRELID1, SMOX, SLC25A4, and DENND1B) that might be closely associated with C. irritans resistance. This study not only provides valuable resources of novel genic transcripts for further research, but also provides new insights into the immune mechanisms underlying C. irritans infection response in farmed fugu.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The cattle industry contributes to Uganda's agricultural output. It faces challenges that include theft and parentage ascertainment. These challenges can benefit from recent molecular genomics and ...bioinformatics technologies.
We employed genomic analyses to establish potential ownership of a group of nine cattle that were being claimed by two farmers in Uganda. We investigated the genetic relationship of Ugandan cattle with regional indigenous breeds as well as exotic breeds that are currently present in Uganda. In addition, we investigated regions that are likely to be under selection in the Ugandan cattle.
Hair samples were collected from seven and two animals from farmers A and B, respectively. They were genotyped for 53,218 Single Nucleotide Polymorphism markers. To establish genetic relationships between the sampled animals, we performed genomic analyses including, principal component analysis (PCA), hierarchical clustering analysis and identity by state/descent. We also performed admixture and runs of homozygosity analyses to assess the ancestry composition and identify regions potentially under selection in Ugandan cattle, respectively.
The seven animals from Farmer A were genetically close to each other but showed minimal relationship with the disputed animals. The two animals from Farmer B were genetically distant from each other but showed greater similarity to four of the disputed animals. Four of the disputed animals showed great dissimilarity from the animals of both farmers. Comparison of these with the reference breeds revealed minimal European exotic genetic introgression into these animals, but rather high similarity to the Sheko. Results also revealed high homozygosity in the major histocompatibility complex regions.
Our results demonstrate the use of currently available genomic tools to empirically establish the ownership of cattle; these could be scaled up as a resourceful and viable tool that could be employed to support conflict resolution where reliable livestock identification is unavailable.
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.
The combination of mRNA and lncRNA profiles for establishing an integrated mRNA–lncRNA prognostic signature has remained unexplored in cholangiocarcinoma (CCA) patients. We utilized a training ...dataset of 36 samples from The Cancer Genome Atlas dataset and a validation cohort (GSE107943) of 30 samples from Gene Expression Omnibus. Two mRNAs ( CFHR3 and PIWIL4 ) and 2 lncRNAs ( AC007285.1 and AC134682.1 ) were identified to construct the integrated signature through a univariate Cox regression ( P -value = 1.35E−02) and a multivariable Cox analysis ( P -value = 3.07E−02). Kaplan–Meier curve showed that patients with low risk scores had notably prolonged overall survival than those with high risk scores ( P -value = 4.61E−03). Subsequently, the signature was validated in GSE107943 cohort with an area under the curve of 0.750 at 1-year and 0.729 at 3-year. The signature was not only independent from diverse clinical features ( P -value = 3.07E−02), but also surpassed other clinical characteristics as prognostic biomarkers with area under the curve of 0.781 at 3-year. Moreover, the weighted gene co-expression network analysis and gene enrichment analyses found that the integrated signature were associated with metabolic-related biological process and lipid metabolism pathway, which has been implicated in the pathogenesis of CCA. Taken together, we developed an integrated mRNA–lncRNA signature that had an independent prognostic value in the risk stratification of patients with CCA.
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