Maternal genes and pathways affecting birth weight and weaning weight traits in sheep: A GWAS and pathway enrichment analysis

Abstract Background Ewe productivity is considered as the most important economic trait in sheep meat production. Due to very limited reports, the objective of this study was the application of alternative GWAS approaches followed by gene set enrichment analysis (GSEA) on the maternal genome to unravel the genomic architecture underlying ewe productivity in Iranian Baluchi sheep. Six maternal composite traits including progeny birth weight (PBW), litter mean weight at birth (LMWB), total litter weight at birth (TLWB), progeny weaning weight (PWW), litter mean weight at weaning (LMWW) and total litter weight at weaning (TLWW) were studied. Results Genes such as RDX , FDX1 , ARHGAP20 , ZC3H12C , THBS1 , and EPG5 on OAR6, OAR7, OAR15, and OAR23 were identified for composite traits at birth. The genes are involved in pregnancy, including autophagy in the placenta, progesterone production by the placenta, maternal immune response and placenta formation. Some maternal pathways, related to calcium ion transport, signal transduction, neurogenesis, and immune response were also identified for birth weight traits. Moreover, many genes including NR2C1 , VEZT , HSD17B4 , RSU1 , CUBN , VIM , PRLR , and FTH1 were located on OAR2, OAR3, OAR5, OAR7, OAR13, OAR16, and OAR25 identified as maternal genes affecting weaning weight traits. Most of the identified genes were involved in mammary glands development and milk components production. Also, many GO terms related to protein processing and transport, ion transport and homeostasis, proteins and lipid phosphorylation, and phospholipid translocation were identified in association with weaning weight traits. Conclusions The results of the present study revealed that calcium ion homeostasis and transport and the maternal immune system could have an important role in progeny’s birth weight. Also, the results showed that genes and pathways affecting mammary glands development during pregnancy and milk components production have the most impact on lambs weaning weight. These findings contribute to a better understanding of the genetic architecture of the studied traits and providing opportunities for improving ewe productivity via marker-assisted selection.

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Genes and Pathways Affecting Sheep Productivity Traits: Genetic Parameters, Genome-Wide Association Mapping, and Pathway Enrichment Analysis

Frontiers in Genetics ◽

10.3389/fgene.2021.710613 ◽

2021 ◽

Vol 12 ◽

Author(s):

Seyed Mehdi Esmaeili-Fard ◽

Mohsen Gholizadeh ◽

Seyed Hasan Hafezian ◽

Rostam Abdollahi-Arpanahi

Keyword(s):

Ion Transport ◽

Calcium Ion ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Genome Wide Association ◽

Meat Production ◽

Pathway Enrichment Analysis ◽

Litter Weight ◽

Genome Wide ◽

Calcium Ion Transport

Ewe productivity is a composite and maternal trait that is considered the most important economic trait in sheep meat production. The objective of this study was the application of alternative genome-wide association study (GWAS) approaches followed by gene set enrichment analysis (GSEA) on the ewes’ genome to identify genes affecting pregnancy outcomes and lamb growth after parturition in Iranian Baluchi sheep. Three maternal composite traits at birth and weaning were considered. The traits were progeny birth weight, litter mean weight at birth, total litter weight at birth, progeny weaning weight, litter mean weight at weaning, and total litter weight at weaning. GWASs were performed on original phenotypes as well as on estimated breeding values. The significant SNPs associated with composite traits at birth were located within or near genes RDX, FDX1, ARHGAP20, ZC3H12C, THBS1, and EPG5. Identified genes and pathways have functions related to pregnancy, such as autophagy in the placenta, progesterone production by the placenta, placental formation, calcium ion transport, and maternal immune response. For composite traits at weaning, genes (NR2C1, VEZT, HSD17B4, RSU1, CUBN, VIM, PRLR, and FTH1) and pathways affecting feed intake and food conservation, development of mammary glands cytoskeleton structure, and production of milk components like fatty acids, proteins, and vitamin B-12, were identified. The results show that calcium ion transport during pregnancy and feeding lambs by milk after parturition can have the greatest impact on weight gain as compared to other effects of maternal origin.

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Increased VEGF-A in solid type of lung adenocarcinoma reduces the patients’ survival

Scientific Reports ◽

10.1038/s41598-020-79907-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Woon Yong Jung ◽

Kyueng-Whan Min ◽

Young Ha Oh

Keyword(s):

Immune Response ◽

Survival Analysis ◽

Lung Adenocarcinoma ◽

Survival Rates ◽

Treatment Strategies ◽

Enrichment Analysis ◽

Genetic Alterations ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Solid Type

AbstractThe histological classification of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival differences between the other types were not significant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.

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Identification of long noncoding RNAs reveals the effects of dinotefuran on the brain in Apis mellifera (Hymenopptera: Apidae)

BMC Genomics ◽

10.1186/s12864-021-07811-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Minjie Huang ◽

Jie Dong ◽

Haikun Guo ◽

Minghui Xiao ◽

Deqian Wang

Keyword(s):

Immune Response ◽

Honey Bee ◽

Honey Bees ◽

Transforming Growth Factor ◽

Sublethal Effects ◽

Inflammatory Responses ◽

Noncoding Rnas ◽

Enrichment Analysis ◽

Long Noncoding Rnas ◽

Gene Set Enrichment Analysis

Abstract Background Dinotefuran (CAS No. 165252–70-0), a neonicotinoid insecticide, has been used to protect various crops against invertebrate pests and has been associated with numerous negative sublethal effects on honey bees. Long noncoding RNAs (lncRNAs) play important roles in mediating various biological and pathological processes, involving transcriptional and gene regulation. The effects of dinotefuran on lncRNA expression and lncRNA function in the honey bee brain are still obscure. Results Through RNA sequencing, a comprehensive analysis of lncRNAs and mRNAs was performed following exposure to 0.01 mg/L dinotefuran for 1, 5, and 10 d. In total, 312 lncRNAs and 1341 mRNAs, 347 lncRNAs and 1458 mRNAs, and 345 lncRNAs and 1155 mRNAs were found to be differentially expressed (DE) on days 1, 5 and 10, respectively. Gene set enrichment analysis (GSEA) indicated that the dinotefuran-treated group showed enrichment in carbohydrate and protein metabolism and immune-inflammatory responses such as glycine, serine and threonine metabolism, pentose and glucuronate interconversion, and Hippo and transforming growth factor-β (TGF-β) signaling pathways. Moreover, the DE lncRNA TCONS_00086519 was shown by fluorescence in situ hybridization (FISH) to be distributed mainly in the cytoplasm, suggesting that it may serve as a competing endogenous RNA and a regulatory factor in the immune response to dinotefuran. Conclusion This study characterized the expression profile of lncRNAs upon exposure to neonicotinoid insecticides in young adult honey bees and provided a framework for further study of the role of lncRNAs in honey bee growth and the immune response.

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Comparative farrowing to weaning performance in Meishan and Large White pigs and their crosses

Animal Science ◽

10.1017/s1357729800008432 ◽

1995 ◽

Vol 60 (2) ◽

pp. 269-280 ◽

Cited By ~ 23

Author(s):

G. J. Lee ◽

C. S. Haley

Keyword(s):

Birth Weight ◽

Standard Deviation ◽

Litter Size ◽

Large White ◽

Weaning Weight ◽

Growth And Survival ◽

Probability Of Survival ◽

Litter Weight ◽

Litter Traits ◽

Breed Differences

AbstractGrowth and survival from birth to weaning were monitored during three generations of crossbreeding between British Large White (LW) and Chinese Meishan (MS) pigs. The design allowed comparisons between sow genotypes ranging from zero to all MS genes, which were mated toLWor MS boars, to produce progeny with proportions of 0·0 to 0·5 or 0·5 to 1·0 MS genes, respectively. Crossbreeding parameters of both maternal and direct piglet performance were estimated for the first two parities using restricted maximum likelihood (REML) methods for litter traits (litter weight at birth, litter mean and within litter standard deviation of piglet weight at birth, proportion surviving to weaning, litter size and weight at weaning and litter mean piglet weight at weaning) and for traits of the piglet (birth weight, probability of survival and weaning weight). For litter traits, the estimated contribution of the additive maternal effect to the breed differences (MS-LW) was significant for litter mean piglet birth weight (–0·46 (s.e. 0·04) kg), survival to weaning (0·15 (s.e. 0·02)), litter size at weaning (1·6 (s.e. 0·16) piglets), litter weaning weight (–11·2 (s.e. 3·8) kg) and litter mean piglet weaning weight (2·54 (s.e. 0·24) kg). Adding litter size and litter mean piglet birth weight to the model removed the additive maternal contribution to the breed differences in survival, and litter size and reduced that for litter mean piglet weaning weight. The contribution of the direct additive effect to the breed difference (MS-LW) was significant for the within litter standard deviation in birth weight (0·018 (s.e. 0·006)), survival to weaning (0·12 (s.e. 0·02)) and litter size (1·12 (s.e. 0·64)) and weight (11·6 (s.e. 4·0) kg) at weaning, but not for piglet weight at birth or weaning. Fitting litter size and litter mean birth weight had comparatively little impact on the direct additive effects. There were significant maternal heterosis effects for litter weight at birth and litter size and weight at weaning, the estimated deviation of the F1 from the midpoint of the two purebreds 3·22 (s.e. 0·55) kg, 2·20 (s.e. 0·47) piglets, and 20·1 (s.e. 3·3) kg respectively, but none for survival or piglet weights. There were direct heterosis effects for litter weight and litter mean piglet weights, the estimated deviation of the Fjfrom the mid point of the two purebreds being 1·16 (s.e. 0·41) kg and 0·14 (s.e. 0·02) kg, for survival to weaning (0·04 (s.e. 0·02)) and for litter weight (11·2 (s.e. 2·5) kg) and litter mean piglet weight (0·96 (s.e. 0·17) kg) at weaning. Fitting litter size and litter mean piglet birth weight removed or reduced both maternal and direct heterosis effects. Individual piglet analyses gave similar results to analyses of the equivalent sow trait. It was concluded that in litters born to MS cows, the lower piglet survival and lower weaning weights were related to the larger litter sizes and lower piglet birth weights. For their birth weight, however, MS piglets have a greater ability to survive and thrive. The large direct and maternal heterosis effects observed for litter and mean piglet weight at weaning werepartly associated with the heavier birth weight of the crossbred piglet.

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Organoids Are Limited in Modeling the Colon Adenoma–Carcinoma Sequence

Cells ◽

10.3390/cells10030488 ◽

2021 ◽

Vol 10 (3) ◽

pp. 488

Author(s):

Yoshihisa Tokumaru ◽

Masanori Oshi ◽

Ankit Patel ◽

Wanqing Tian ◽

Li Yan ◽

...

Keyword(s):

Colorectal Cancer ◽

Immune Response ◽

Immune Cells ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Related Gene ◽

Gene Set Enrichment ◽

Colon Adenoma ◽

Tissue Samples ◽

Gene Sets

The colon adenoma–carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma–carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma–carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cells were different between tissues and organoids, whereas there was no difference between cancer and adenoma organoids. The amounts of cancer stem cells and progenitor cells were not different between CRC and adenoma organoids, whereas a difference was noted between CRC and adenoma tissues. In conclusion, we demonstrated that organoids model only part of the adenoma–carcinoma sequence and should be used with caution after considering their limitations.

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miR-154 Influences HNSCC Development and Progression through Regulation of the Epithelial-To-Mesenchymal Transition Process and Could Be Used as a Potential Biomarker

Biomedicines ◽

10.3390/biomedicines9121894 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1894

Author(s):

Weronika Tomaszewska ◽

Joanna Kozłowska-Masłoń ◽

Dawid Baranowski ◽

Anna Perkowska ◽

Sandra Szałkowska ◽

...

Keyword(s):

Immune Response ◽

Epithelial To Mesenchymal Transition ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Functional Enrichment ◽

Clinicopathological Parameters ◽

Mesenchymal Transition ◽

Diagnostic Potential ◽

Potential Biomarker

MicroRNAs and their role in cancer have been extensively studied for the past decade. Here, we analyzed the biological role and diagnostic potential of miR-154-5p and miR-154-3p in head and neck squamous cell carcinoma (HNSCC). miRNA expression analyses were performed using The Cancer Genome Atlas (TCGA) data accessed from cBioPortal, UALCAN, Santa Cruz University, and Gene Expression Omnibus (GEO). The expression data were correlated with clinicopathological parameters. The functional enrichment was assessed with Gene Set Enrichment Analysis (GSEA). The immunological profiles were assessed using the ESTIMATE tool and RNAseq data from TCGA. All statistical analyses were performed with GraphPad Prism and Statistica. The study showed that both miR-154-5p and miR-154-3p were downregulated in the HNSCC samples and their expression levels correlated with tumor localization, overall survival, cancer stage, tumor grade, and HPV p16 status. GSEA indicated that individuals with the increased levels of miR-154 had upregulated AKT-MTOR, CYCLIN D1, KRAS, EIF4E, RB, ATM, and EMT gene sets. Finally, the elevated miR-154 expression correlated with better immune response. This study showed that miR-154 is highly involved in HNSCC pathogenesis, invasion, and immune response. The implementation of miR-154 as a biomarker may improve the effectiveness of HNSCC treatment.

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Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus

10.1101/2021.10.07.21264642 ◽

2021 ◽

Author(s):

Jamie A Sugrue ◽

Megan Smith ◽

Celine Posseme ◽

Bruno Charbit ◽

Nollaig M Bourke ◽

...

Keyword(s):

Immune Response ◽

Influenza A Virus ◽

Influenza A ◽

Viral Infections ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Human Immunology ◽

Specific Effects ◽

Specific Analysis ◽

D Antigen

The Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of RhD on immune responses. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 30 differentially expressed genes (DEGs) between RhD-positive (n=401) and RhD-negative males (n=78). Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.

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Significance of KDM6A mutation in bladder cancer immune escape

BMC Cancer ◽

10.1186/s12885-021-08372-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xingxing Chen ◽

Xuehua Lin ◽

Guofu Pang ◽

Jian Deng ◽

Qun Xie ◽

...

Keyword(s):

Immune Response ◽

Bladder Cancer ◽

Immune Escape ◽

Tumour Progression ◽

Mrna Level ◽

Enrichment Analysis ◽

Cancer Genome ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Recurrence Rates

Abstract Background Bladder cancer (BC) is the fourth most prevalent neoplasm in men and is associated with high tumour recurrence rates, leading to major treatment challenges. Lysine-specific demethylase 6A (KDM6A) is frequently mutated in several cancer types; however, its effects on tumour progression and clinical outcome in BC remain unclear. Here, we explored the potential role of KDM6A in regulating the antitumor immune response. Methods We mined The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases for somatic mutation and clinical data in patients with BC. Results We found frequent mutations in 12 genes in both cohorts, including TP53, KDM6A, CSMD3, MUC16, STAG2, PIK3CA, ARID1A, RB1, EP300, ERBB2, ERBB3, and FGFR3. The frequency o KDM6A mutations in the TCGA and ICGC datasets was 25.97 and 24.27%, respectively. In addition, KDM6A mutation was associated with a lower number of tumour-infiltrating immune cells (TIICs) and indicated a state of immune tolerance. KDM6A mutation was associated with lower KDM6A mRNA level compared with that in samples carrying the wild-type gene. Further, survival analysis showed that the prognosis of patients with low KDM6A expression was worse than that with high KDM6A expression. Using the CIBERSORT algorithm, Tumor Immune Estimation Resource site, and Gene Set Enrichment Analysis, we found that KDM6A mutation downregulated nine signalling pathways that participate in the immune system and attenuated the tumour immune response. Conclusion Overall, we conclude that KDM6A mutation is frequent in BC and promotes tumour immune escape, which may serve as a novel biomarker to predict the immune response.

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Expression Profile Analysis of Selenium-Related Genes in Peripheral Blood Mononuclear Cells of Patients with Keshan Disease

BioMed Research International ◽

10.1155/2019/4352905 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Xiaojuan Liu ◽

Shulan He ◽

Juanxia Peng ◽

Xiong Guo ◽

Wuhong Tan

Keyword(s):

Ion Transport ◽

Growth And Development ◽

Mononuclear Cells ◽

Expression Profiles ◽

Single Gene ◽

Selenium Deficiency ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Keshan Disease ◽

Peripheral Blood Mononuclear

Keshan disease (KD) is an endemic cardiomyopathy, which mainly occurs in China. Selenium deficiency is believed to play an important role in the pathogenesis of KD, but the molecular mechanism of selenium-induced damage remains unclear. To identify the key genes involved in selenium-induced damage, we compared the expression profiles of selenium-related genes between patients with KD and normal controls. Total RNA was isolated, amplified, labeled, and hybridized to Agilent human 4 × 44 K whole genome microarrays. Selenium-related genes were screened using the Comparative Toxicogenomics Database. The microarray data were subjected to single-gene and gene ontology (GO) expression analysis using R Studio and Gene Set Enrichment Analysis (GSEA) software. Quantitative real-time PCR was conducted to validate the microarray results. We identified 16 upregulated and 11 downregulated selenium-related genes in patients. These genes are involved in apoptosis, metabolism, transcription regulation, ion transport, and growth and development. Of the significantly enriched GO categories in KD patients, we identified four apoptosis-related, two metabolism-related, four growth and development-related, and four ion transport-related GOs. Based on our results, we suggest that selenium might contribute to the development of KD through dysfunction of selenium-related genes involved in apoptosis, metabolism, ion transport, and growth and development in the myocardium.

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2595. Murine Models for the Host Response to Typical and Atypical Pneumonia

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2273 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S902-S902

Author(s):

Kirin Khan ◽

Marisol Betancourt-Quiroz ◽

Aimee K Zaas ◽

Amy E Treece ◽

Loretta G Que ◽

...

Keyword(s):

Immune Response ◽

Post Infection ◽

Host Response ◽

Human Subjects ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Atypical Pneumonia ◽

Murine Models ◽

Strong Immune Response ◽

Viral Response

Abstract Background The etiology of pneumonia is difficult to diagnose, with typical bacterial, atypical bacterial, and viral infections being the most common. However, diagnostics that discriminate these infectious etiologies are limited. We, therefore, focused on the host response to identify possible diagnostic markers and better understand these infections. However, atypical bacterial pneumonia is challenging to identify in humans precisely because of this diagnostic difficulty. Therefore, we utilized murine models to define host response differences between typical bacterial, atypical bacterial, and viral pneumonia. Methods Mice were intranasally inoculated with S. pneumoniae (n = 38), M. pneumoniae (n = 27), H1N1 pr8 (n = 19), or saline as a control (n = 42). RNA was extracted from peripheral blood collected at 24, 48, 72, 120, or 168 hours and subjected to microarray analysis. Diagnostic signatures were generated using lasso logistic regression and accuracy was assessed using nested leave-one-out cross-validation with feature selection repeated within each iteration. Differentially expressed genes were used to perform gene set enrichment analysis. These murine-derived signatures were externally validated in silico in 487 human subjects found across 5 publicly available data sets. Results We generated pathogen-specific murine disease signatures that performed with 91–100% accuracy. Pathway analysis revealed that animals with pneumococcal pneumonia had a robust immune response by 48 hours that continued to 72 hours post-infection. In contrast, animals infected with M. pneumoniae did not show evidence of a strong immune response until 72-hours post-infection. Additionally, the immune response to M. pneumoniae bared greater similarity to the viral response than it did to the host pneumococcal response. H1N1-infected mice showed an anti-viral response at 120 hours that resolved by 168 hours post-infection. The AUC values resulting from independent human validation of our murine signatures ranged from 89 to 98%. Conclusion There are discrete host responses to typical bacterial, atypical bacterial, and viral etiologies of pneumonia in mice. These signatures validate well in humans, highlighting the conserved nature of the host response to these pathogen classes. Disclosures Ephraim L. Tsalik, MD MHS PhD, Immunexpress: Consultant; Predigen, Inc.: Officer or Board Member, Research Grant.

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