Publications by authors named "Huaijun Zhou"

112 Publications

Tissue Resources for the Functional Annotation of Animal Genomes.

Front Genet 2021 21;12:666265. Epub 2021 Jun 21.

UC Davis Department of Animal Science, University of California, Davis, Davis, CA, United States.

In order to generate an atlas of the functional elements driving genome expression in domestic animals, the Functional Annotation of Animal Genome (FAANG) strategy was to sample many tissues from a few animals of different species, sexes, ages, and production stages. This article presents the collection of tissue samples for four species produced by two pilot projects, at INRAE (National Research Institute for Agriculture, Food and Environment) and the University of California, Davis. There were three mammals (cattle, goat, and pig) and one bird (chicken). It describes the metadata characterizing these reference sets (1) for animals with origin and selection history, physiological status, and environmental conditions; (2) for samples with collection site and tissue/cell processing; (3) for quality control; and (4) for storage and further distribution. Three sets are identified: set 1 comprises tissues for which collection can be standardized and for which representative aliquots can be easily distributed (liver, spleen, lung, heart, fat depot, skin, muscle, and peripheral blood mononuclear cells); set 2 comprises tissues requiring special protocols because of their cellular heterogeneity (brain, digestive tract, secretory organs, gonads and gametes, reproductive tract, immune tissues, cartilage); set 3 comprises specific cell preparations (immune cells, tracheal epithelial cells). Dedicated sampling protocols were established and uploaded in https://data.faang.org/protocol/samples. Specificities between mammals and chicken are described when relevant. A total of 73 different tissues or tissue sections were collected, and 21 are common to the four species. Having a common set of tissues will facilitate the transfer of knowledge within and between species and will contribute to decrease animal experimentation. Combining data on the same samples will facilitate data integration. Quality control was performed on some tissues with RNA extraction and RNA quality control. More than 5,000 samples have been stored with unique identifiers, and more than 4,000 were uploaded onto the Biosamples database, provided that standard ontologies were available to describe the sample. Many tissues have already been used to implement FAANG assays, with published results. All samples are available without restriction for further assays. The requesting procedure is described. Members of FAANG are encouraged to apply a range of molecular assays to characterize the functional status of collected samples and share their results, in line with the FAIR (Findable, Accessible, Interoperable, and Reusable) data principles.
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http://dx.doi.org/10.3389/fgene.2021.666265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256271PMC
June 2021

Primary Chicken and Duck Endothelial Cells Display a Differential Response to Infection with Highly Pathogenic Avian Influenza Virus.

Genes (Basel) 2021 Jun 10;12(6). Epub 2021 Jun 10.

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Australia.

Highly pathogenic avian influenza viruses (HPAIVs) in gallinaceous poultry are associated with viral infection of the endothelium, the induction of a 'cytokine storm, and severe disease. In contrast, in Pekin ducks, HPAIVs are rarely endothelial tropic, and a cytokine storm is not observed. To date, understanding these species-dependent differences in pathogenesis has been hampered by the absence of a pure culture of duck and chicken endothelial cells. Here, we use our recently established in vitro cultures of duck and chicken aortic endothelial cells to investigate species-dependent differences in the response of endothelial cells to HPAIV H5N1 infection. We demonstrate that chicken and duck endothelial cells display a different transcriptional response to HPAI H5N1 infection in vitro-with chickens displaying a more pro-inflammatory response to infection. As similar observations were recorded following in vitro stimulation with the viral mimetic polyI:C, these findings were not specific to an HPAIV H5N1 infection. However, similar species-dependent differences in the transcriptional response to polyI:C were not observed in avian fibroblasts. Taken together, these data demonstrate that chicken and duck endothelial cells display a different response to HPAIV H5N1 infection, and this may help account for the species-dependent differences observed in inflammation in vivo.
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http://dx.doi.org/10.3390/genes12060901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230508PMC
June 2021

Reply to "Letter to the Editor" by Cem Yener et al.

Arch Gynecol Obstet 2021 Jun 26. Epub 2021 Jun 26.

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People's Republic of China.

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http://dx.doi.org/10.1007/s00404-021-06135-2DOI Listing
June 2021

Large-Scale Multiplexing Permits Full-Length Transcriptome Annotation of 32 Bovine Tissues From a Single Nanopore Flow Cell.

Front Genet 2021 20;12:664260. Epub 2021 May 20.

Department of Animal Science, University of California, Davis, Davis, CA, United States.

A comprehensive annotation of transcript isoforms in domesticated species is lacking. Especially considering that transcriptome complexity and splicing patterns are not well-conserved between species, this presents a substantial obstacle to genomic selection programs that seek to improve production, disease resistance, and reproduction. Recent advances in long-read sequencing technology have made it possible to directly extrapolate the structure of full-length transcripts without the need for transcript reconstruction. In this study, we demonstrate the power of long-read sequencing for transcriptome annotation by coupling Oxford Nanopore Technology (ONT) with large-scale multiplexing of 93 samples, comprising 32 tissues collected from adult male and female Hereford cattle. More than 30 million uniquely mapping full-length reads were obtained from a single ONT flow cell, and used to identify and characterize the expression dynamics of 99,044 transcript isoforms at 31,824 loci. Of these predicted transcripts, 21% exactly matched a reference transcript, and 61% were novel isoforms of reference genes, substantially increasing the ratio of transcript variants per gene, and suggesting that the complexity of the bovine transcriptome is comparable to that in humans. Over 7,000 transcript isoforms were extremely tissue-specific, and 61% of these were attributed to testis, which exhibited the most complex transcriptome of all interrogated tissues. Despite profiling over 30 tissues, transcription was only detected at about 60% of reference loci. Consequently, additional studies will be necessary to continue characterizing the bovine transcriptome in additional cell types, developmental stages, and physiological conditions. However, by here demonstrating the power of ONT sequencing coupled with large-scale multiplexing, the task of exhaustively annotating the bovine transcriptome - or any mammalian transcriptome - appears significantly more feasible.
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http://dx.doi.org/10.3389/fgene.2021.664260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173071PMC
May 2021

Tolerogenic Immunoregulation towards Salmonella Enteritidis Contributes to Colonization Persistence in Young Chicks.

Infect Immun 2021 Jul 15;89(8):e0073620. Epub 2021 Jul 15.

Department of Animal Science, University of California, Davis, California, USA.

Long-term survival and the persistence of bacteria in the host suggest either host unresponsiveness or induction of an immunological tolerant response to the pathogen. The role of the host immunological response to persistent colonization of Salmonella Enteritidis (SE) in chickens remains poorly understood. In the current study, we performed a cecal tonsil transcriptome analysis in a model of SE persistent infection in 2-week-old chickens to comprehensively examine the dynamics of host immunological responses in the chicken gastrointestinal tract. Our results revealed overall host tolerogenic adaptive immune regulation in a major gut-associated lymphoid tissue, the cecal tonsil, during SE infection. Specifically, we observed consistent downregulation of the metallothionein 4 gene at all four postinfection time points (3, 7, 14, and 21 days postinfection [dpi]), which suggested potential pathogen-associated manipulation of the host zinc regulation as well as a possible immune modulatory effect. Furthermore, delayed activation in the B cell receptor signaling pathway and failure to sustain its active state during the lag phase of infection were further supported by an insignificant production of both intestinal and circulatory antibodies. Tug-of-war for interleukin 2 (IL-2) regulation between effector T cells and regulatory T cells appears to have consequences for upregulation in the transducer of ERBB2 (TOB) pathway, a negative regulator of T cell proliferation. In conclusion, this work highlights the overall host tolerogenic immune response that promotes persistent colonization by SE in young layer chicks.
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http://dx.doi.org/10.1128/IAI.00736-20DOI Listing
July 2021

Comparison of cellular immune responses to avian influenza virus in two genetically distinct, highly inbred chicken lines.

Vet Immunol Immunopathol 2021 May 24;235:110233. Epub 2021 Mar 24.

Department of Animal Science, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA, United States. Electronic address:

Low pathogenicity avian influenza causes mild disease involving the respiratory, gastrointestinal, and reproductive systems of wild and domestic birds. Avian influenza research often emphasizes the effect of the virus genetics on disease, but the influence of host genetics on resistance to infection is not well understood. The genetic determinants of enhanced resistance to influenza can be explored by using genetically distinct, highly inbred chicken lines that differ in susceptibility to influenza. In this study, we compared the mucosal cellular immune responses between the relatively resistant Fayoumi M43 chicken line and the relatively susceptible Leghorn GB2 chicken line after challenging with low pathogenicity avian influenza virus (LPAIV) H6N2. The birds were inoculated at 21 days of age with 10 50 % egg infective dose (EID) LPAIV H6N2 via nasal and tracheal routes in two separate experiments. Clinical signs were recorded, tracheal swabs were collected to measure viral titer, and tracheas and lungs were harvested for flow cytometric analysis of macrophage, B cell, and T cell populations at 4 days post-infection (dpi) (Experiments 1 and 2) and 6 dpi (Experiment 2). Blood and tears were also collected at 7 and 14 dpi (Experiment 1) to measure antibody levels. Compared to both the non-challenged Fayoumis and the relatively susceptible Leghorn chickens, relatively resistant Fayoumi chickens challenged with LPAIV demonstrated enhanced MHC class I expression on antigen-presenting cells and increased macrophage, B cell, and T cell frequencies in the trachea, which were associated with reduced tracheal viral titers at 4 dpi. In contrast, MHC class I expression and immune cell frequencies in the trachea were not different between challenged Leghorns and non-challenged Leghorns. Furthermore, Leghorns shed higher virus titers in their trachea compared to Fayoumis. Challenged Fayoumis and Leghorns both produced AIV-specific IgY detected in the serum and tears, but AIV-specific IgA was not detected in the tears. In this study, we provide new insight into immune mechanisms of enhanced resistance to avian influenza in chickens, which may lead to improved vaccination strategies and breeding programs.
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http://dx.doi.org/10.1016/j.vetimm.2021.110233DOI Listing
May 2021

Distinct transcriptomic response to Newcastle disease virus infection during heat stress in chicken tracheal epithelial tissue.

Sci Rep 2021 Apr 2;11(1):7450. Epub 2021 Apr 2.

Feed the Future Innovation Lab for Genomics to Improve Poultry, University of California, Davis, CA, 95616, USA.

Newcastle disease (ND) has a great impact on poultry health and welfare with its most virulent (velogenic) strain. In addition, issues exacerbated by the increase in global temperatures necessitates a greater understanding of the host immune response when facing a combination of biotic and abiotic stress factors in poultry production. Previous investigations have revealed that the host immune response is tissue-specific. The goal of this study was to identify genes and/or signaling pathways associated with immune response to NDV (Newcastle disease virus) in the trachea, an essential organ where NDV replicate after the infection, by profiling the tissue specific transcriptome response in two genetically distinct inbred chicken lines when exposed to both abiotic and biotic stressors. Fayoumis appear to be able to respond more effectively (lower viral titer, higher antibody levels, immune gene up-regulation) and earlier than Leghorns. Our results suggest NDV infection in Fayoumis appears to elicit proinflammatory processes, and pathways such as the inhibition of cell viability, cell proliferation of lymphocytes, and transactivation of RNA, more rapidly than in Leghorns. These differences in immune response converge at later timepoints which may indicate that Leghorns eventually regulate its immune response to infection. The profiling of the gene expression response in the trachea adds to our understanding of the chicken host response to NDV infection and heat stress on a whole genome level and provides potential candidate genes and signaling pathways for further investigation into the characterization of the time-specific and pathway specific responses in Fayoumis and Leghorns.
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http://dx.doi.org/10.1038/s41598-021-86795-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018950PMC
April 2021

Functional annotations of three domestic animal genomes provide vital resources for comparative and agricultural research.

Nat Commun 2021 03 23;12(1):1821. Epub 2021 Mar 23.

Department of Animal Science, University of California, Davis, Davis, CA, USA.

Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.
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http://dx.doi.org/10.1038/s41467-021-22100-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988148PMC
March 2021

Transcription initiation mapping in 31 bovine tissues reveals complex promoter activity, pervasive transcription, and tissue-specific promoter usage.

Genome Res 2021 Apr 15;31(4):732-744. Epub 2021 Mar 15.

Department of Animal Science, University of California, Davis, California 95616, USA.

Characterizing transcription start sites is essential for understanding the regulatory mechanisms that control gene expression. Recently, a new bovine genome assembly (ARS-UCD1.2) with high continuity, accuracy, and completeness was released; however, the functional annotation of the bovine genome lacks precise transcription start sites and contains a low number of transcripts in comparison to human and mouse. By using the RAMPAGE approach, this study identified transcription start sites at high resolution in a large collection of bovine tissues. We found several known and novel transcription start sites attributed to promoters of protein-coding and lncRNA genes that were validated through experimental and in silico evidence. With these findings, the annotation of transcription start sites in cattle reached a level comparable to the mouse and human genome annotations. In addition, we identified and characterized transcription start sites for antisense transcripts derived from bidirectional promoters, potential lncRNAs, mRNAs, and pre-miRNAs. We also analyzed the quantitative aspects of RAMPAGE to produce a promoter activity atlas, reaching highly reproducible results comparable to traditional RNA-seq. Coexpression networks revealed considerable use of tissue-specific promoters, especially between brain and testicle, which expressed several genes in common from alternate loci. Furthermore, regions surrounding coexpressed modules were enriched in binding factor motifs representative of each tissue. The comprehensive annotation of promoters in such a large collection of tissues will substantially contribute to our understanding of gene expression in cattle and other mammalian species, shortening the gap between genotypes and phenotypes.
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http://dx.doi.org/10.1101/gr.267336.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015843PMC
April 2021

Construction of a Glycolysis-related long noncoding RNA signature for predicting survival in endometrial cancer.

J Cancer 2021 1;12(5):1431-1444. Epub 2021 Jan 1.

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

long noncoding RNA (lncRNA) has been widely studied and understood in various cancer types. However, the expression profiles of glycolysis-related lncRNA in endometrial cancer (EC) have poorly been reported. In this study, we retrieved the "Glycolysis" gene list from Molecular Signatures Database (MSigDB) and screened prognostic glycolysis-related lncRNA using The Cancer Genome Atlas (TCGA) Uterine Corpus Endometrial Carcinoma (UCEC) RNA-seq dataset. Then, TCGA UCEC patients were randomly divided. Lasso algorithm and multivariate cox regression analyses were then performed to further select hub prognostic lncRNA and to develop a prognostic signature. The efficacy of the signature was also evaluated in the TCGA EC cohort. Moreover, we constructed a nomogram to predict EC patient outcomes. Univariate cox analysis identified thirty-six glycolysis-related lncRNA correlated with EC patient prognosis. Among them, five lncRNA were further selected as hub lncRNA that mostly relate to EC patient outcomes, which are AL121906.2, BOLA3-AS1, LINC01833, AC016405.3, and RAB11B-AS1. A prognostic signature was then built based on the expression and coefficiency of five lncRNA. The efficacy of the signature was validated in part of and the entire TCGA EC cohort. In addition, the risk signature could precisely distinguish high- and low-risk EC patients and predict patient outcomes. The nomogram exhibited absolute concordance between the predictions and actual survival observations. The glycolysis-related lncRNA signature model and the nomogram may provide a new perspective for EC patients outcome prediction in clinical use.
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http://dx.doi.org/10.7150/jca.50413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847640PMC
January 2021

Surgical outcomes of cesarean scar pregnancy: an 8-year experience at a single institution.

Arch Gynecol Obstet 2021 05 3;303(5):1223-1233. Epub 2021 Jan 3.

Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, People's Republic of China.

Purpose: To summarize the outcomes of different surgical treatment modalities for cesarean scar pregnancy (CSP) at a single institution over 8 years.

Methods: A case series of patients diagnosed with CSP who were admitted to Nanjing Drum Tower Hospital from January 2011 to December 2018 was retrospectively studied. Medical records of all the patients were carefully reviewed. Data on patient demographics, pregnancy characteristics, treatment modalities, response to therapy, and subsequent pregnancy outcomes were collected and analyzed.

Results: A total of 117 patients undergoing surgical treatments for CSP were included. Thirty-three patients (28.21%) underwent ultrasound-guided curettage; while, 74 (63.25%) and 10 (8.55%) patients received laparoscopy-monitored curettage and laparoscopic CSP resection, respectively. Most of the patients (21/33) who underwent ultrasound-guided surgery had type I CSP; while, 54 out of 84 patients who opted for laparoscopic surgeries had type II CSP. Eleven women underwent a uterine artery embolization procedure before the operation. There was no difference in the use of an intrauterine balloon for hemostasis among the three groups. Only 8 patients needed additional systemic methotrexate treatment. Twenty-four out of 57 women (42.11%) succeeded in conceiving again and gave birth to 21 healthy babies. Only 1 woman (1/24, 4.17%) experienced recurrence of CSP.

Conclusions: These data indicated the safety and efficiency of ultrasound-guided curettage, laparoscopy-monitored curettage, and laparoscopic CSP resection for the treatment of CSP.
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http://dx.doi.org/10.1007/s00404-020-05906-7DOI Listing
May 2021

Cerebellar nuclei evolved by repeatedly duplicating a conserved cell-type set.

Science 2020 12;370(6523)

Department of Biology, Stanford University, Stanford, CA 94305, USA.

How have complex brains evolved from simple circuits? Here we investigated brain region evolution at cell-type resolution in the cerebellar nuclei, the output structures of the cerebellum. Using single-nucleus RNA sequencing in mice, chickens, and humans, as well as STARmap spatial transcriptomic analysis and whole-central nervous system projection tracing, we identified a conserved cell-type set containing two region-specific excitatory neuron classes and three region-invariant inhibitory neuron classes. This set constitutes an archetypal cerebellar nucleus that was repeatedly duplicated to form new regions. The excitatory cell class that preferentially funnels information to lateral frontal cortices in mice becomes predominant in the massively expanded human lateral nucleus. Our data suggest a model of brain region evolution by duplication and divergence of entire cell-type sets.
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http://dx.doi.org/10.1126/science.abd5059DOI Listing
December 2020

MTA1, a Target of Resveratrol, Promotes Epithelial-Mesenchymal Transition of Endometriosis via ZEB2.

Mol Ther Methods Clin Dev 2020 Dec 28;19:295-306. Epub 2020 Sep 28.

Department of Gynecology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China.

Endometriosis is a benign disease that shares some malignant features. Epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of endometriosis. Metastasis-associated protein 1 (MTA1) plays an important role in various cancers by promoting EMT, yet there are no studies on its function in endometriosis. In the present study, we found that MTA1 was highly expressed in the ectopic endometrium of endometriosis patients and that the expression of MTA1 was related to the revised American Fertility Society stage. MTA1 facilitated endometrial stroma cell proliferation, migration, and invasion by inducing EMT, and the promotion function and MTA1 expression were suppressed by resveratrol, a natural polyphenol. Moreover, we revealed that MTA1 induced EMT through interaction with ZEB2. The findings in a mouse endometriosis model further showed that MTA1 and ZEB2 were upregulated in ectopic tissues and that resveratrol inhibited the growth of ectopic lesions and expression of MTA1 and ZEB2. Taken together, we demonstrate that MTA1 is a protein that promotes EMT via interacting with ZEB2 in the pathogenesis of endometriosis, and may be a target of resveratrol.
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http://dx.doi.org/10.1016/j.omtm.2020.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578554PMC
December 2020

Integrated Transcriptome and Histone Modification Analysis Reveals NDV Infection Under Heat Stress Affects Bursa Development and Proliferation in Susceptible Chicken Line.

Front Genet 2020 25;11:567812. Epub 2020 Sep 25.

Department of Animal Science, University of California, Davis, Davis, CA, United States.

Two environmental factors, Newcastle disease and heat stress, are concurrently negatively impacting poultry worldwide and warrant greater attention into developing genetic resistance within chickens. Using two genetically distinct and highly inbred layer lines, Fayoumi and Leghorn, we explored how different genetic backgrounds affect the bursal response to a treatment of simultaneous Newcastle disease virus (NDV) infection at 6 days postinfection (dpi) while under chronic heat stress. The bursa is a primary lymphoid organ within birds and is crucial for the development of B cells. We performed RNA-seq and ChIP-seq targeting histone modifications on bursa tissue. Differential gene expression revealed that Leghorn, compared to Fayoumi, had significant down-regulation in genes involved in cell proliferation, cell cycle, and cell division. Interestingly, we also found greater differences in histone modification levels in response to treatment in Leghorns than Fayoumis, and biological processes enriched in associated target genes of H3K27ac and H3K4me1 were similarly associated with cell cycle and receptor signaling of lymphocytes. Lastly, we found candidate variants between the two genetic lines within exons of differentially expressed genes and regulatory elements with differential histone modification enrichment between the lines, which provides a strong foundation for understanding the effects of genetic variation on NDV resistance under heat stress. This study provides further understanding of the cellular mechanisms affected by NDV infection under heat stress in chicken bursa and identified potential genes and regulatory regions that may be targets for developing genetic resistance within chickens.
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http://dx.doi.org/10.3389/fgene.2020.567812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545831PMC
September 2020

A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues.

BMC Genomics 2020 Oct 7;21(1):698. Epub 2020 Oct 7.

Department of Animal Science, University of California Davis, Davis, CA, 95616, USA.

Background: Although considerable progress has been made towards annotating the noncoding portion of the human and mouse genomes, regulatory elements in other species, such as livestock, remain poorly characterized. This lack of functional annotation poses a substantial roadblock to agricultural research and diminishes the value of these species as model organisms. As active regulatory elements are typically characterized by chromatin accessibility, we implemented the Assay for Transposase Accessible Chromatin (ATAC-seq) to annotate and characterize regulatory elements in pigs and cattle, given a set of eight adult tissues.

Results: Overall, 306,304 and 273,594 active regulatory elements were identified in pig and cattle, respectively. 71,478 porcine and 47,454 bovine regulatory elements were highly tissue-specific and were correspondingly enriched for binding motifs of known tissue-specific transcription factors. However, in every tissue the most prevalent accessible motif corresponded to the insulator CTCF, suggesting pervasive involvement in 3-D chromatin organization. Taking advantage of a similar dataset in mouse, open chromatin in pig, cattle, and mice were compared, revealing that the conservation of regulatory elements, in terms of sequence identity and accessibility, was consistent with evolutionary distance; whereas pig and cattle shared about 20% of accessible sites, mice and ungulates only had about 10% of accessible sites in common. Furthermore, conservation of accessibility was more prevalent at promoters than at intergenic regions.

Conclusions: The lack of conserved accessibility at distal elements is consistent with rapid evolution of enhancers, and further emphasizes the need to annotate regulatory elements in individual species, rather than inferring elements based on homology. This atlas of chromatin accessibility in cattle and pig constitutes a substantial step towards annotating livestock genomes and dissecting the regulatory link between genome and phenome.
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http://dx.doi.org/10.1186/s12864-020-07078-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541309PMC
October 2020

Phenotypic variability and population structure analysis of Tanzanian free-range local chickens.

BMC Vet Res 2020 Sep 29;16(1):360. Epub 2020 Sep 29.

Department of Veterinary Medicine and Public Health, Sokoine University of Agriculture, Morogoro, Tanzania.

Background: Free-range local chickens (FRLC) farming is an important activity in Tanzania, however, they have not been well-characterized. This study aimed to phenotypically characterize three Tanzanian FRLCs and to determine their population structure. A total of 389 mature breeder chickens (324 females and 65 males) from three popular Tanzanian FRLC ecotypes (Kuchi, Morogoro-medium and Ching'wekwe) were used for the phenotypic characterization. Progenies of these chickens were utilized to assess population structure. The ecotypes were collected from four geographical zones across Tanzania: Lake, Central, Northern and Coastal zones. Body weights and linear measurements were obtained from the mature breeders, including body, neck, shanks, wingspan, chest girth, and shank girth. Descriptive statistics were utilized to characterize the chickens. Correlations between the linear measurements and differences among the means of measured linear traits between ecotypes and between sexes were assessed. A total of 1399 progeny chicks were genotyped using a chicken 600 K high density single nucleotide polymorphism (SNP) panel for determination of population structure.

Results: The means for most traits were significantly higher in Kuchi relative to Ching'wekwe and Morogoro-medium. However, shank length and shank girth were similar between Kuchi and Morogoro-medium females. All traits were correlated with the exception of shank girth in Morogoro-medium. Admixture analyses revealed that Morogoro-medium and Ching'wekwe clustered together as one population, separate from Kuchi.

Conclusions: Phenotypic traits could be used to characterize FRLCs, however, there were variations in traits among individuals within ecotypes; therefore, complementary genomic methods should be considered to improve the characterization for selective breeding.
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http://dx.doi.org/10.1186/s12917-020-02541-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523039PMC
September 2020

Liver Transcriptome Responses to Heat Stress and Newcastle Disease Virus Infection in Genetically Distinct Chicken Inbred Lines.

Genes (Basel) 2020 09 11;11(9). Epub 2020 Sep 11.

Department of Animal Science, University of California, Davis, CA 95616, USA.

Heat stress results in reduced productivity, anorexia, and mortality in chickens. The objective of the study was to identify genes and signal pathways associated with heat stress and Newcastle disease virus (NDV) infection in the liver of chickens through RNA-seq analysis, using two highly inbred chicken lines (Leghorn and Fayoumi). All birds were held in the same environment until 14 days of age. On day 14, half the birds were exposed to 38 °C with 50% relative humidity for 4 h, then 35 °C until the end of the experiment. The remaining birds were kept at 25 °C throughout the experiment. The heat-treated birds were inoculated at 21 days of age with 10 EID (One EID unit is the amount of virus that will infect 50 percent of inoculated embryos) NDV La Sota strain to investigate the effects of both heat stress and NDV infection. Physiological parameters were recorded as blood phenotypes at three stages: acute heat (AH), chronic heat (CH1), and chronic heat combined with NDV infection (CH&NDV), at 4 h, 7 days, and 10 days post-initiation of heat treatment, respectively. Our previous work revealed that the heat-resilient Fayoumi line maintained a more stable acid-base balance in their blood compared to the Leghorn line. Liver samples were harvested on both AH and CH&NDV to characterize the transcriptome profiles of these two inbred lines. Both genetic lines and treatments had large impact on the liver transcriptome. Fayoumi birds had more differentially expressed genes (DEGs) than Leghorn birds for both treatments. Metabolic and immune-related genes were on the DEG list, with Fayoumi having more immune-related DEGs than Leghorns, which was confirmed by gene functional enrichment analysis. Weighted correlation network analysis (WGCNA) indicated that the driver genes such as Solute Carrier Family genes could be very important for stabilizing the acid-base balance in Fayoumi birds during heat stress. Therefore, candidate genes such solute carrier family genes could be potential genetic targets that are regulated by Fayoumis to maintain physical hemostasis under heat stress. Differential gene expression showed that Leghorns mainly performed metabolic regulation in response to heat stress and NDV infection, while Fayoumis regulated both immune and metabolic functions. This study provides novel insights and enhances our understandings of liver response to heat stress of heat resilient and susceptible inbred chicken lines.
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http://dx.doi.org/10.3390/genes11091067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563548PMC
September 2020

Transcriptome Analysis Reveals Inhibitory Effects of Lentogenic Newcastle Disease Virus on Cell Survival and Immune Function in Spleen of Commercial Layer Chicks.

Genes (Basel) 2020 08 26;11(9). Epub 2020 Aug 26.

Department of Animal Science, Iowa State University, Ames, IA 50011, USA.

As a major infectious disease in chickens, Newcastle disease virus (NDV) causes considerable economic losses in the poultry industry, especially in developing countries where there is limited access to effective vaccination. Therefore, enhancing resistance to the virus in commercial chickens through breeding is a promising way to promote poultry production. In this study, we investigated gene expression changes at 2 and 6 days post inoculation (dpi) at day 21 with a lentogenic NDV in a commercial egg-laying chicken hybrid using RNA sequencing analysis. By comparing NDV-challenged and non-challenged groups, 526 differentially expressed genes (DEGs) (false discovery rate (FDR) < 0.05) were identified at 2 dpi, and only 36 at 6 dpi. For the DEGs at 2 dpi, Ingenuity Pathway Analysis predicted inhibition of multiple signaling pathways in response to NDV that regulate immune cell development and activity, neurogenesis, and angiogenesis. Up-regulation of interferon induced protein with tetratricopeptide repeats 5 () in response to NDV was consistent between the current and most previous studies. Sprouty RTK signaling antagonist 1 (), a DEG in the current study, is in a significant quantitative trait locus associated with virus load at 6 dpi in the same population. These identified pathways and DEGs provide potential targets to further study breeding strategy to enhance NDV resistance in chickens.
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http://dx.doi.org/10.3390/genes11091003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565929PMC
August 2020

Genetic Basis of Response of Ghanaian Local Chickens to Infection With a Lentogenic Newcastle Disease Virus.

Front Genet 2020 28;11:739. Epub 2020 Jul 28.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Newcastle disease (ND) is a global threat to domestic poultry, especially in rural areas of Africa and Asia, where the loss of entire backyard local chicken flocks often threatens household food security and income. To investigate the genetics of Ghanaian local chicken ecotypes to Newcastle disease virus (NDV), in this study, three popular Ghanaian chicken ecotypes (regional populations) were challenged with a lentogenic NDV strain at 28 days of age. This study was conducted in parallel with a similar study that used three popular Tanzanian local chicken ecotypes and after two companion studies in the United States, using Hy-line Brown commercial laying birds. In addition to growth rate, NDV response traits were measured following infection, including anti-NDV antibody levels [pre-infection and 10 days post-infection (dpi)], and viral load (2 and 6 dpi). Genetic parameters were estimated, and two genome-wide association study analysis methods were used on data from 1,440 Ghanaian chickens that were genotyped on a chicken 600K Single Nucleotide Polymorphism (SNP) chip. Both Ghana and Tanzania NDV challenge studies revealed moderate to high (0.18 - 0.55) estimates of heritability for all traits, except viral clearance where the heritability estimate was not different from zero for the Tanzanian ecotypes. For the Ghana study, 12 quantitative trait loci (QTL) for growth and/or response to NDV from single-SNP analyses and 20 genomic regions that explained more than 1% of genetic variance using the Bayes B method were identified. Seven of these windows were also identified as having at least one significant SNP in the single SNP analyses for growth rate, anti-NDV antibody levels, and viral load at 2 and 6 dpi. An important gene for growth during stress, CHORDC1 associated with post-infection growth rate was identified as a positional candidate gene, as well as other immune related genes, including VAV2, IL12B, DUSP1, and IL17B. The QTL identified in the Ghana study did not overlap with those identified in the Tanzania study. However, both studies revealed QTL with genes vital for growth and immune response during NDV challenge. The Tanzania parallel study revealed an overlapping QTL on chromosome 24 for viral load at 6 dpi with the US NDV study in which birds were challenged with NDV under heat stress. This QTL region includes genes related to immune response, including TIRAP, ETS1, and KIRREL3. The moderate to high estimates of heritability and the identified QTL suggest that host response to NDV of local African chicken ecotypes can be improved through selective breeding to enhance increased NDV resistance and vaccine efficacy.
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http://dx.doi.org/10.3389/fgene.2020.00739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402339PMC
July 2020

Molecular Characterization of Newcastle Disease Viruses Isolated from Chickens in Tanzania and Ghana.

Viruses 2020 08 20;12(9). Epub 2020 Aug 20.

Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

Newcastle disease (ND) is one of the most challenging infectious diseases affecting poultry production in Africa, causing major economic losses. To date, Newcastle disease virus isolates from several African countries have been grouped into class II NDV genotypes I, IV, V, VI, VII, XI, XIII, XIV, XVII, XVIII and XXI. Although ND is endemic in many African countries, information on circulating genotypes is still scarce. In Tanzania, outbreaks with genotypes V and XIII have been reported. In West and Central Africa, genotypes XIV, XVII, and XVIII are the most predominant. To investigate other genotypes circulating in Tanzania and Ghana, we performed molecular genotyping on isolates from Tanzania and Ghana using the MinION, a third-generation portable sequencing device from Oxford Nanopore Technologies. Using the MinION, we successfully sequenced the NDV F gene hypervariable region of 24 isolates from Tanzania and four samples from Ghana. In Tanzania, genotypes V, VII and XIII were detected. All isolates from Ghana belonged to genotype XVIII. The data obtained in this study reflect the genetic diversity of NDV in Africa and highlight the importance of surveillance for monitoring the distribution of NDV genotypes and viral evolution.
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http://dx.doi.org/10.3390/v12090916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551648PMC
August 2020

Genetic responses of inbred chicken lines illustrate importance of eIF2 family and immune-related genes in resistance to Newcastle disease virus.

Sci Rep 2020 04 9;10(1):6155. Epub 2020 Apr 9.

Department of Animal Science, Iowa State University, Ames, IA, USA.

Newcastle disease virus (NDV) replication depends on the translation machinery of the host cell; therefore, the eukaryotic translation initiation factor 2 (eIF2) gene family is a likely candidate for control of viral replication. We hypothesized that differential expression of host genes related to translation and innate immune response could contribute to differential resistance to NDV in inbred Fayoumi and Leghorn lines. The expression of twenty-one genes related to the interferon signaling pathway and the eIF2 family was evaluated at two- and six-days post infection (dpi) in the spleen from both lines, either challenged by NDV or nonchallenged. Higher expression of OASL in NDV challenged versus nonchallenged spleen was observed in Leghorns at 2 dpi. Lower expression of EIF2B5 was found in NDV challenged than nonchallenged Fayoumis and Leghorns at 2 dpi. At 2 dpi, NDV challenged Fayoumis had lower expression of EIF2B5 and EIF2S3 than NDV challenged Leghorns. At 6 dpi, NDV challenged Fayoumis had lower expression of EIF2S3 and EIF2B4 than NDV challenged Leghorns. The genetic line differences in expression of eIF2-related genes may contribute to their differential resistance to NDV and also to understanding the interaction between protein synthesis shut-off and virus control in chickens.
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http://dx.doi.org/10.1038/s41598-020-63074-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145804PMC
April 2020

Knockout of IRF7 Highlights its Modulator Function of Host Response Against Avian Influenza Virus and the Involvement of MAPK and TOR Signaling Pathways in Chicken.

Genes (Basel) 2020 04 2;11(4). Epub 2020 Apr 2.

Department of Animal Science, University of California, Davis, CA 95616, USA.

Interferon regulatory factor 7 (IRF7) is known as the master transcription factor of the type I interferon response in mammalian species along with IRF3. Yet birds only have IRF7, while they are missing IRF3, with a smaller repertoire of immune-related genes, which leads to a distinctive immune response in chickens compared to in mammals. In order to understand the functional role of IRF7 in the regulation of the antiviral response against avian influenza virus in chickens, we generated chicken embryonic fibroblast (DF-1) cell lines and respective controls () by utilizing the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system. IRF7 knockout resulted in increased viral titers of low pathogenic avian influenza viruses. Further RNA-sequencing performed on H6N2-infected and cell lines revealed that the deletion of IRF7 resulted in the significant down-regulation of antiviral effectors and the differential expression of genes in the MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) signaling pathways. Dynamic gene expression profiling of the host response between the wildtype and IRF7 knockout revealed potential signaling pathways involving (activator protein 1), (nuclear factor kappa B) and inflammatory cytokines that may complement chicken IRF7. Our findings in this study provide novel insights that have not been reported previously, and lay a solid foundation for enhancing our understanding of the host antiviral response against the avian influenza virus in chickens.
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http://dx.doi.org/10.3390/genes11040385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230310PMC
April 2020

Integrative analysis of gut microbiome and metabolites revealed novel mechanisms of intestinal Salmonella carriage in chicken.

Sci Rep 2020 03 16;10(1):4809. Epub 2020 Mar 16.

Department of Animal Science, University of California, Davis, CA, 95616, USA.

Intestinal carriage of Salmonella Enteritidis (SE) in the chicken host serves as a reservoir for transmission of Salmonella to humans through the consumption of poultry products. The aim of the current study was to examine the three-way interaction that occurred between host metabolites, resident gut microbiota and Salmonella following inoculation of SE in two-week-old layer chicks. Our results revealed an overall alteration in gut microbiome and metabolites in association with SE infection. Enriched colonization by different microbial members throughout the course of experimental infection highlighted significant fluctuation in the intestinal microbial community in response to Salmonella infection. As changes in community membership occurred, there was also subsequent impact on differential regulation of interlinked predicted functional activities within the intestinal environment dictated by Salmonella-commensal interaction. Alteration in the overall microbial community following infection also has a ripple effect on the host regulation of cecum-associated metabolic networks. The findings showed that there was differential regulation in many of the metabolites in association with SE colonization in chickens. Perturbation in metabolic pathways related to arginine and proline metabolism as well as TCA cycle was most prominently detected. Taken together, the present findings provided a starting point in understanding the effect of intestinal Salmonella carriage on the microbiome and metabolome of developing young layer chicks.
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http://dx.doi.org/10.1038/s41598-020-60892-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075953PMC
March 2020

Novel Combined Tissue Transcriptome Analysis After Lentogenic Newcastle Disease Virus Challenge in Inbred Chicken Lines of Differential Resistance.

Front Genet 2020 4;11:11. Epub 2020 Feb 4.

Department of Animal Science, Iowa State University, Ames, IA, United States.

Disease has large negative impacts on poultry production. A more comprehensive understanding of host-pathogen interaction can lead to new and improved strategies to maintain health. In particular, host genetic factors can lead to a more effective response to pathogens, hereafter termed resistance. Fayoumi and Leghorn chicken lines have demonstrated relative resistance and susceptibility, respectively, to the Newcastle disease virus (NDV) vaccine strain and many other pathogens. This biological model was used to better understand the host response to a vaccine strain of NDV across three tissues and time points, using RNA-seq. Analyzing the Harderian gland, trachea, and lung tissues together using weighted gene co-expression network analysis (WGCNA) identified important genes that were co-expressed and associated with parameters including: genetic line, days post-infection (dpi), challenge status, sex, and tissue. Pathways and driver genes, such as , , and , associated with challenge status, dpi, and genetic line were of particular interest as candidates for disease resistance. Overall, by jointly analyzing the three tissues, this study identified genes and gene networks that led to a more comprehensive understanding of the whole animal response to lentogenic NDV than that obtained by analyzing the tissues individually.
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http://dx.doi.org/10.3389/fgene.2020.00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013128PMC
February 2020

Women's knowledge of and attitudes toward cervical cancer and cervical cancer screening in Zanzibar, Tanzania: a cross-sectional study.

BMC Cancer 2020 Jan 28;20(1):63. Epub 2020 Jan 28.

Department of Obstetrics & Gynecology, Nanjing Drum Tower Hospital, Affiliated to Nanjing University Medical College, Nanjing, 210008, China.

Background: Cervical cancer is the most common cancer and the leading cause of cancer death among women in Tanzania. Knowledge of and willingness to receive a cervical cancer screening are important determinants of prevention. This study aimed to describe women's awareness of cervical cancer and to explore the attitudes toward, acceptability of and barriers to cervical cancer screening (CCS) in Zanzibar.

Methods: A cross-sectional study was conducted from March to June 2018 involving 1483 women from 10 districts in Zanzibar who responded to questionnaires concerning their general demo-graphic characteristics, screening willingness and awareness of cervical cancer. Chi-square tests, analysis of variance (ANOVA) and stepwise multiple regression were conducted using STATA 15.1 software.

Results: The average total knowledge score (TKS) was 7.84 ± 5.32 on a 23-point scale. Educational level and family income were positively correlated with the TKS. Previous schistosomiasis history and family genetic disease history were strong predictors of screening willingness. Women were less likely to be screened freely if they had 7 or more deliveries and were unaware of any previous family tumor history. Age and educational level were negatively associated non-free screening willingness, while family income was positively associated; being divorced/widowed or single and being unaware of any previous family tumor history were predictors of screening reluctance, while previous disease history was a strong predictor of non-free screening willingness. Fear of screening and inconvenience were the primary concerns among the Zanzibari interviewees. Compared to the 20-49 age group, more women in the less than 20 and 50 or more age groups thought cervical cancer screening was not necessary. The highest rate of cognitive accuracy in regard to cervical cancer warning signs and risk factors was only 37.76%.

Conclusions: The findings revealed that knowledge of cervical cancer was poor. Educational level, family income and awareness of previous disease history were significant influencing factors of screening uptake. Specific awareness programs to increase knowledge of cervical cancer and screening willingness should be designed and implemented in the public without delay, especially for younger and elderly women.
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http://dx.doi.org/10.1186/s12885-020-6528-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988189PMC
January 2020

Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.

Genes (Basel) 2019 12 18;11(1). Epub 2019 Dec 18.

Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.

One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to map four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3) in eight prioritized tissues collected as part of the FAANG equine biobank from two thoroughbred mares. Data were generated according to optimized experimental parameters developed during quality control testing. To ensure that we obtained sufficient ChIP and successful peak-calling, data and peak-calls were assessed using six quality metrics, replicate comparisons, and site-specific evaluations. Tissue specificity was explored by identifying binding motifs within unique active regions, and motifs were further characterized by gene ontology (GO) and protein-protein interaction analyses. The histone marks identified in this study represent some of the first resources for tissue-specific regulation within the equine genome. As such, these publicly available annotation data can be used to advance equine studies investigating health, performance, reproduction, and other traits of economic interest in the horse.
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http://dx.doi.org/10.3390/genes11010003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017286PMC
December 2019

miRNA-mRNA Associated With Survival in Endometrial Cancer.

Front Genet 2019 20;10:743. Epub 2019 Aug 20.

Department of Gynecology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Although various factors may contribute to its initiation and progression, the etiology and prognostic factors of endometrial carcinoma (EC) remains not fully understood. We sought to understand the role of changes in transcriptome during the progress of EC by exploring public datasets. The aberrant expression characteristics of EC based on RNA-Seq and miRNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed. Kaplan-Meier analysis was performed to assess the relationship between differently expressed genes (DEGs) and patient survival. As a result, 320 out of 4,613 differently expressed mRNAs (DE mRNAs) and 68 out of 531 differently expressed miRNAs (DE miRNAs) with a significantly poorer survival were determined. We predicted eight paired DE miRNAs and DE mRNAs through TargetScan. Patients with three out of the eight paired low rate of miRNA/mRNA (miR-497/EMX1, miR-23c/DMBX1, and miR-670/KCNS1) expression had a significantly poorer survival. Furthermore, the simultaneous presence of these selected low miRNA/mRNA pairs occurred in most patients and resulted in a significantly poorer survival rate. Luciferase reporter assay identified that EMX1 was a direct target of miR-497. Both low expression of miR-497 and overexpression of EMX1 were significantly associated with more advanced clinicopathologic characteristics (stage, tumor status, grade, and histology) besides survival (all P values < 0.05). Multivariate analysis also demonstrated that miR-497 remained an independent prognostic variable for overall survival. In summary, we identified that a series of DE mRNAs and miRNAs, including eight paired DE miRNAs and mRNAs, were associated with survival in EC. Clinical evaluation of downregulated miR-497 and paired upregulated EMX1 confirmed the value of our prediction analysis. The simultaneous presence of low rate of these selected low miRNA/mRNA pairs (miR-497/EMX1, miR-23c/DMBX1, and miR-670/KCNS1) might have a better prediction value. Therefore, further studies are required to validate these findings.
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http://dx.doi.org/10.3389/fgene.2019.00743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710979PMC
August 2019

Genetic Analyses of Tanzanian Local Chicken Ecotypes Challenged with Newcastle Disease Virus.

Genes (Basel) 2019 07 17;10(7). Epub 2019 Jul 17.

Department of Animal Science, Iowa State University, 2255 Kildee Hall, Ames, IA 50011, USA.

Newcastle Disease (ND) is a continuing global threat to domestic poultry, especially in developing countries, where severe outbreaks of velogenic ND virus (NDV) often cause major economic losses to households. Local chickens are of great importance to rural family livelihoods through provision of high-quality protein. To investigate the genetic basis of host response to NDV, three popular Tanzanian chicken ecotypes (regional populations) were challenged with a lentogenic (vaccine) strain of NDV at 28 days of age. Various host response phenotypes, including anti-NDV antibody levels (pre-infection and 10 days post-infection, dpi), and viral load (2 and 6 dpi) were measured, in addition to growth rate. We estimated genetic parameters and conducted genome-wide association study analyses by genotyping 1399 chickens using the Affymetrix 600K chicken SNP chip. Estimates of heritability of the evaluated traits were moderate (0.18-0.35). Five quantitative trait loci (QTL) associated with growth and/or response to NDV were identified by single-SNP analyses, with some regions explaining ≥1% of genetic variance based on the Bayes-B method. Immune related genes, such as ETS1, TIRAP, and KIRREL3, were located in regions associated with viral load at 6 dpi. The moderate estimates of heritability and identified QTL indicate that NDV response traits may be improved through selective breeding of chickens to enhance increased NDV resistance and vaccine efficacy in Tanzanian local ecotypes.
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http://dx.doi.org/10.3390/genes10070546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678660PMC
July 2019

A Homeostasis Hypothesis of Avian Influenza Resistance in Chickens.

Genes (Basel) 2019 07 17;10(7). Epub 2019 Jul 17.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Avian influenza has caused significant damage to the poultry industry globally. Consequently, efforts have been made to elucidate the disease mechanisms as well as the mechanisms of disease resistance. Here, by investigating two chicken breeds with distinct responses to avian influenza virus (AIV), Leghorn GB2 and Fayoumi M43, we compared their genome, methylation, and transcriptome differences. , and exhibited high degrees of genetic differentiation (F) between the two species. Except for the -involved direct anti-virus mechanism, we found that at the methylation and transcriptome levels, the more AIV-resistant breed, Fayoumi, exhibited less variation compared with Leghorn after AIV inoculation, which included change trends in differentially expressed regions, top-fold change genes with FDR-corrected < 0.05, immune response related genes, and housekeeping genes. Fayoumi also showed better consistency regarding changes in methylation and changes at the transcriptome level. Our results suggest a homeostasis hypothesis for avian influenza resistance, with Fayoumi maintaining superior homeostasis at both the epigenetic and gene expression levels. Three candidate genes-, and -showed genetic differentiation and altered gene expression, methylation, and protein expression, which merit attention in further functional studies.
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http://dx.doi.org/10.3390/genes10070543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678902PMC
July 2019

Effects of Chicken MHC Haplotype on Resistance to Distantly Related Infectious Bronchitis Viruses.

Avian Dis 2019 06;63(2):310-317

Department of Population Health and Reproduction, School of Veterinary Medicine, 4009 VM3B, University of California-Davis, Davis, CA 95616,

The major histocompatibility complex (MHC) B locus of chickens has been associated with resistance to different viral diseases. We previously provided evidence that chicken lines expressing MHC haplotypes B2 and B19 exhibit different resistance to a challenge with infectious bronchitis virus (IBV) Massachusetts 41 (M41). In the current study, we attempted to determine if those differences were true for genetically diverse IB viruses, i.e., IBV M41 and Arkansas-Delmarva poultry industry (ArkDPI). Clinical, pathologic, molecular, and immunologic outcomes were compared. Our results showed subtle clinical and pathologic differences between the two MHC chicken lines tested. Clinical differences were observed in respiratory signs at 2 days postinfection (dpi) in M41-infected birds. Pathologic differences were detected in viral load at 2 dpi in M41-infected birds and in tracheal epithelial thickness at 6 dpi in ArkDPI-infected birds. Substantial differences were observed in antibody responses at 14 dpi. The transcriptome analysis showed that B19 chickens highly expressed genes related to inflammatory and innate immune responses. This increased immune gene expression detected in B19 birds at 6 dpi did not lead to enhanced antibody production at 14 dpi. On the other hand, B2-haplotype chickens highly expressed genes related to cell responses, suggesting that B2 is able to diligently control the infection. Although not identical, genes triggered by M41 and ArkDPI are part of communal pathways and suggest similar immune and cell responses to both IBV genotypes. This work provides modest evidence for differential resistance to IBV by chickens displaying different MHC haplotypes as well as insights into the expression of a variety of genes after IBV replication in the host.
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http://dx.doi.org/10.1637/11989-103118-Reg.1DOI Listing
June 2019