Source: UNIVERSITY OF CALIFORNIA, DAVIS submitted to NRP
GENETIC BASES FOR RESISTANCE AND IMMUNITY TO AVIAN DISEASES
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
1018147
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
NE-1834
Project Start Date
Oct 31, 2018
Project End Date
Sep 30, 2023
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Performing Department
Animal Science
Non Technical Summary
Disease resistance has a significant economic impact on poultry industry. The highly inbred chicken lines with distinct resistance and susceptibility to Newcastle disease and avian influenza virus infection will be used for the proposed study. High throughput technology including RNA-seq, ChIP-seq will be employed to identify genes and signal pathways associated with disease resistance. Immune related parameters will be evaluated. The results will enhance our understanding of gene function and expression and their associations with disease resistance in poultry; Genetic variations identified can be used to improve genetic selection programs at the primary poultry breeding companies by utilization of modern, cost-efficient breeding practices based on marker-assisted selection.
Animal Health Component
15%
Research Effort Categories
Basic
75%
Applied
15%
Developmental
10%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3033220104030%
3043220105040%
3053299108030%
Goals / Objectives
To determine how allelic variation influences the efficacy of innate and acquired immune functions. To identify factors and agents affecting poultry immune development, function, dysfunction, and pathology. To develop and employ genetic stocks, methods, reagents, and other tools to assess basic immune function, characterize immune evolutionary processes, guide genetic selection, and increase resistance to or protection against avian diseases.
Project Methods
For the objective 1:Genetically distinct highly inbred lines will be used, RNA-seq will be used to identify genetic variations and differentially expressed genes with Salmonella, Newcastle disease virus, avian influenza virus, and different immune parameters will be used to evaluate disease resistance. The associations of genetic variations and immune parameters will be analyzed.For the objective 2: Heat stress and pathogens such as avian influenza virus and Newcastle disease virus will be used challenge highly inbred chicken lines or commercial chickens to evaluate effect of these stressors on immune function and disease resistance. RNA-seq will be applied to examine gene expression profile and signaling pathways related to immune function.For the objective 3: ChIP-seq, ATAC-seq, and Hi-C assays will be developed and optimized in different immune related tissues such as spleen, lung, bursa, trachea to evaluate epigenetic effect on disease resistance to Newcastle disease and avian influenza virus infection in two highly inbred chicken lines. The assays developed can be applied in other tissues.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:poultry scientific community, 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? 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. 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. 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. 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). 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.

Publications

  • Type: Journal Articles Status: Published Year Published: 2020 Citation: Walugembe M, Amuzu-Aweh EN, P. K. Botchway, A. Naazie, G. Aning, Wang Y, Saelao P, Kelly T, Gallardo RA, Zhou H, Lamont SJ, Kayang B.B., Dekkers JCM. 2020. Genetic Basis of Response of Ghanaian Local Chickens to Infection With a Lentogenic Newcastle Disease Virus. Front. Genet., https://doi.org/10.3389/fgene.2020.00739.
  • 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: 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.


Progress 10/31/18 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 candidategenes 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. 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. ?

Publications

  • 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: 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: 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.
  • 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: 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: 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.