Progress 10/01/19 to 09/30/20
Outputs
Target Audience:livestock and poultry scientific community, livestock and poultry industry Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Graduate students, undergraduate students, and postdoctoral scholar have training in in animal genetics, bioinformatics and genomic analysis. How have the results been disseminated to communities of interest?Oral and poster presentations were given in scientific meetings, and institutes in the US, Czech. Participated in workshop with diverse participants including scientists from institutes, funding agencies, NGO. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
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. 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 IRF7-/- chicken embryonic fibroblast (DF-1) cell lines and respective controls (IRF7wt) 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 IRF7-/- and IRF7wt 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 AP1 (activator protein 1), NF-κB (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.
Publications
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Halstead M., C. Kern, Saelao, P. G. Chanthavixay, Y. Wang, J.F. Medrano, A.L. Van eenennaam, I Korf, C.K. Tuggle, C.W. Ernst, H. Zhou, P. Ross. 2020. A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues. BMC Genomics . 21(1):698. doi: 10.1186/s12864-020-07078-9.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Kingsley NB, Kern C, Creppe C, Hales EN, Zhou H, Kalbfleisch TS, MacLeod JN, Petersen JL, Finno CJ, Bellone RR.2019. Functionally annotating regulatory elements in the equine genome using histone mark ChIP-seq. Genes (Basel). 11(1). pii: E3. doi: 10.3390/genes11010003.
- Type:
Books
Status:
Published
Year Published:
2020
Citation:
S. E. Aggrey, H. Zhou, M. Tixier-Boichard and D. D. Rhoads (Eds). 2020. Advances in poultry genetics and genomics Burleigh Dodds Science Publishing ISBN:978-1-78676-324-2
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Chanthavixay, K., C. Kern, Y. Wang, Saelao, P., R. Gallardo, S.J. Lamont, G. Rincon, Zhou, H. 2020. Integrated Transcriptome and Histone Modification Analysis Reveals NDV Infection Under Heat Stress Affects Bursa Development and Proliferation in Susceptible Chicken Line. Frontiers in Genetics. http://doi.org/10.3389/fgene.2020.567812
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Wang, Y, Saelao, K. Chanthavixay P., R. Gallardo, D,A, Bunn, S.J. Lamont. J.K. Dekkers, T. R. Kelly, Zhou, H. 2020. Liver Transcriptome Responses to Heat Stress and Newcastle Disease Virus Infection in Genetically Distinct Chicken Inbred Lines. Genes 11(9), 1067; https://doi.org/10.3390/genes11091067.
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Kim, T.H., C. Kern, and H. Zhou. 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 11, 385; doi:10.3390/genes11040385
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
K. K.Z. Mon, Y. Zhu, G. Chanthavixay, C. Kern and H. Zhou. 2020. Integrative analysis of gut microbiome and metabolites revealed novel mechanisms of intestinal Salmonella carriage in chicken. Sci Rep. 10, Article number: 4809. www.nature.com/articles/s41598-020-60892-9
- Type:
Journal Articles
Status:
Published
Year Published:
2020
Citation:
Halstead M., C. Kern, Saelao, P. G. Chanthavixay, Y. Wang, M. Delany, H. Zhou, P. Ross. 2020. Systematic alteration of ATAC-seq for profiling open chromatin in cryopreserved nuclei preparations from livestock tissues. Sci Rep 10, Article number: 5230. https://www.nature.com/articles/s41598-020-61678-9
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Progress 10/01/18 to 09/30/19
Outputs
Target Audience:Poultry scientific community, poultry industry Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?Graduate students, undergraduate students, and postdoctoral scholar have training in in poultry disease, immunology and genomic analysis. How have the results been disseminated to communities of interest?Oral and poster presentations were given in scientific meetings, and institutes in the US, Italy, Spain, and Africa. Participated in workshop with diverse participants including scientists from institutes, funding agencies, NGO. Oral presentation was given to disadvantaged students and staff in Africa institutes. What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
§ Newcastle disease virus (NDV) is a highly contagious avian pathogen that poses a tremendous threat to poultry producers in endemic zones due to its epidemic potential. To investigate host genetic resistance to NDV while under the effects of heat stress, a genome-wide association study (GWAS) was performed on Hy-Line Brown layer chickens that were challenged with NDV while under high ambient temperature to identify regions associated with host viral titer, circulating anti-NDV antibody titer, and body weight change. A single nucleotide polymorphism (SNP) on chromosome 1 was associated with viral titer at two days post-infection (dpi), while 30 SNPs spanning a quantitative trait loci (QTL) on chromosome 24 were associated with viral titer at 6 dpi. Immune related genes, such as CAMK1d and CCDC3 on chromosome 1, associated with viral titer at 2 dpi, and TIRAP, ETS1, and KIRREL3, associated with viral titer at 6 dpi, were located in two QTL regions for viral titer that were identified in this study. This study identified genomic regions and candidate genes that are associated with response to NDV during heat stress in Hy-Line Brown layer chickens. Regions identified for viral titer on chromosome 1 and 24, at 2 and 6 dpi, respectively, included several genes that have key roles in regulating the immune response. § Completed genome-wide association analysis for challenge experiments on Hy-Line Brown: All three replicate trials with over 1,100 challenged birds were completed at UCD and ISU. NDV titers were measured in tears collected at 2 and 6 days post infection. In addition, NDV serum antibody response was measured at 10 days post-infection. The major findings were that the 600K SNP panel and GWAS identified few significant regions associated with the measured phenotypes and these were generally of low genetic effect, emphasizing the highly polygenic nature of the NDV response traits. Additional regions of marginal significance were supported by independent studies that demonstrated differential expression in resistant-susceptible line contrasts of genes that were in the QTL regions.
Publications
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Kern, C. P. Y. Wang, P. Saelao, K. Chanthavixay , I. Korf, M. Delany, H. Cheng, J. Ross, Zhou, H. 2019. Allele-specific chromatin accessibility and histone modifications in an F1 cross of MDV resistant and susceptible chicken lines. 37th Conference for the International Society of Animal Genetics, Lleida, Spain
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Halstead M., Kern, C. P. Y. Wang, P. Saelao, S. M. Waters, X. Xu. I. Korf, M. Delany, H. Cheng, J. F. Medrano, A. Van Eenennaam, C. K. Tuggle, C. W. Ernst. Zhou, H. J. Ross. 2019. Identification of orthologous tissue-specific enhancer-gene pairs across chicken, pig and cattle. 37th Conference for the International Society of Animal Genetics, Lleida, Spain
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Kern, C. P. S. M. Waters, X. Xu. I. Korf, M. Delany, H. Cheng, J. F. Medrano, A. Van Eenennaam, C. K. Tuggle, C. W. Ernst. J. Ross, Zhou, H.Zhou, H. Comparison of epigenomes from eight bovine tissues identify regulatory elements with tissue-specific activity. 2019. Keystone Symposia Conference: Epigenetics and Human Disease, Banff, Alberta, Canada.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Kern, C. P. Y. Wang, P. Saelao, S. M. Waters, X. Xu. I. Korf, M. Delany, H. Cheng, J. F. Medrano, A. Van Eenennaam, C. K. Tuggle, C. W. Ernst. J. Ross, Zhou, H. 2019. Correlating Gene Expression with the Histone Modifications H3K4me3 and H3K27ac in High and Low CpG Content Promoters of Chickens, Cattle, and Pigs. Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Chanthavixay, K., C. Kern, Y. Wang, Saelao, P., R. Gallardo, S.J. Lamont. N. Chubb, G. Rincon, Zhou, H. 2019. Differential H3K27ac peaks within bursa tissue of two inbred chicken lines under NDV infection and heat stress. 37th Conference for the International Society of Animal Genetics, Lleida, Spain.
Chanthavixay, K., C. Kern, Y. Wang, Saelao, P., R. Gallardo, S.J. Lamont. N. Chubb, G. Rincon, Zhou, H. 2019. Differential H3K27ac peaks within bursa tissue of two inbred chicken lines under NDV infection and heat stress. 37th Conference for the International Society of Animal Genetics, Lleida, Spain.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Walugembe, M., E.N. Amuzu-Aweh, B.B. Kayang, A.P. Muhairwa, P.K. Botchway, J.R. Mushi, G. Honorati, A. Naazie, G. Aning, P. Msoffe, Y. Wang, P. Saelao, T.R. Kelly, R.A. Gallardo, H. Zhou, S.J. Lamont and J.C.M. Dekkers. 2019. Genetic Analyses of Ghana and Tanzania Local Chicken Ecotypes Challenged with Newcastle Disease Virus. Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Kim, T. H., C. Kern, H. Zhou. 2019. Transcription Factor IRF7 Knockout Revealed Selective Modulation of Type I Interferon Response to Avian Influenza Virus Infection in Chickens. Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Zhou, H. S.J. Lamont, J.C.M. Dekkers, R. Gallardo, T.R. Kelly, B.B. Kayang, A. Naazie, G. Aning, P. Msoffe and A.P. Muhairwa. 2019. Improving Food Security in Africa by Enhancing Resistance to Newcastle Disease and Heat Stress in Chickens (Genomics to Improve Poultry Innovation Lab). Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Wang, Y. Saelao, P., K. Chanthavixay, K. Rowland. T.R. Kelly, J.M. Dekkers, A. Wolc. R. Gallardo, S.J. Lamont. Zhou, H. 2019. Association Analysis with 600K SNP Array Identifies Candidate Genes for Heat Stress Response in Hy-Line Brown Chicks. Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
K. Chanthavixay, C. Kern, Y. Wang, Saelao, P., R. Gallardo, S.J. Lamont. N. Chubb, G. Rincon, Zhou, H. 2019. Predicting Chromatin States to Identify Distinct Active Enhancers Within Bursa Tissue of Two Inbred Chicken Lines Under NDV Infection and Heat Stress. Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
K. Chanthavixay, C. Kern, Y. Wang, Saelao, P., R. Gallardo, S.J. Lamont. N. Chubb, G. Rincon, Zhou, H. 2019. Differential H3K27ac peaks within bursa tissue of two inbred chicken lines under NDV infection and heat stress. Keystone conference in Transcription and RNA Regulation in Inflammation and Immunity, Lake Tahoe, CA
- Type:
Conference Papers and Presentations
Status:
Published
Year Published:
2019
Citation:
Kim, T. H., C. Kern, H. Zhou. 2019. Transcription Factor IRF7 Knockout Revealed Selective Modulation of Type I Interferon Response to Avian Influenza Virus Infection in Chickens. Plant & Animal Genome XXVII, San Diego, CA.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Walugembe M, Mushi JR, Amuzu-Aweh EN, Chiwanga GH, Msoffe PL, Wang Y, Saelao P, Kelly T, Gallardo RA, Zhou H, Lamont SJ, Muhairwa AP, Dekkers JCM. 2019. Genetic Analyses of Tanzanian Local Chicken Ecotypes Challenged with Newcastle Disease Virus. Genes (Basel). 2019 Jul 17;10(7). pii: E546. doi: 10.3390/genes10070546.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Giuffra E, Tuggle CK; Archibald AL, Acloque H, Chamberlain AJ, Cochrane G, Daetwyler HD, Djebali S, Eory L, Foissac S, Goddard ME, Groenen MA, Halstead M, Harrison PW, Hayes BJ, Kern C, Khatib H, Kuo RI, MacHugh DE, Macleod IM, Madsen O, Reecy JM, Ross PJ, Watson M, Wells JM, Zhou H. 2019. Functional Annotation of Animal Genomes (FAANG): Current Achievements and Roadmap. Annu Rev Anim Biosci. 7:65-88. doi: 10.1146/annurev-animal-020518-114913.
- Type:
Journal Articles
Status:
Published
Year Published:
2019
Citation:
Saelao, P., Y. Wang, G. Chanthavixay, J. Dekkers, R. Gallardo, A. Wolc. T.R. Kelly, S.J. Lamont. Zhou, H. 2019. Genetics and Genomic Regions Affecting Response to Newcastle Disease Virus Infection under Heat Stress in Layer Chickens. Genes (Basel). 2019 Jan 18;10(1). pii: E61. doi: 10.3390/genes10010061.
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