Skip to main content Accessibility help

Identifying the genetic basis for resistance to avian influenza in commercial egg layer chickens

  • W. Drobik-Czwarno (a1) (a2), A. Wolc (a2) (a3), J. E. Fulton (a3), J. Arango (a3), T. Jankowski (a4), N. P. O’Sullivan (a3) and J. C. M. Dekkers (a2)...


Two highly pathogenic avian influenza (HPAI) outbreaks have affected commercial egg production flocks in the American continent in recent years; a H7N3 outbreak in Mexico in 2012 that caused 70% to 85% mortality and a H5N2 outbreak in the United States in 2015 with over 99% mortality. Blood samples were obtained from survivors of each outbreak and from age and genetics matched non-affected controls. A total of 485 individuals (survivors and controls) were genotyped with a 600 k single nucleotide polymorphism (SNP) array to detect genomic regions that influenced the outcome of highly pathogenic influenza infection in the two outbreaks. A total of 420458 high quality, segregating SNPs were identified across all samples. Genetic differences between survivors and controls were analyzed using a logistic model, mixed models and a Bayesian variable selection approach. Several genomic regions potentially associated with resistance to HPAI were identified, after performing multidimensional scaling and adjustment for multiple testing. Analysis conducted within each outbreak identified different genomic regions for resistance to the two virus strains. The strongest signals for the Iowa H5N2 survivor samples were detected on chromosomes 1, 7, 9 and 15. Positional candidate genes were mainly coding for plasma membrane proteins with receptor activity and were also involved in immune response. Three regions with the strongest signal for the Mexico H7N3 samples were located on chromosomes 1 and 5. Neuronal cell surface, signal transduction and immune response proteins coding genes were located in the close proximity of these regions.


Corresponding author


Hide All
Balasubramaniam, VRMT, Wai, TH, Omar, AR, Othman, I and Hassan, SS 2012. Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection. Virology Journal 9, 53.
Barrett, JC, Fry, B, Maller, J and Daly, MJ 2005. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263265.
Browning, SR and Browning, BL 2007. Rapid and accurate haplotype phasing and missing data inference for whole genome association studies by use of localized haplotype clustering. American Journal of Human Genetics 81, 10841097.
Burggraaf, S, Karpala, A, Bingham, J, Lowther, S, Selleck, P, Kimpton, W and Bean, A 2014. H5N1 infection causes rapid mortality and high cytokine levels in chickens compared to ducks. Virus Research 185, 2331.
Cornelissen, JB, Vervelde, L, Post, J and Rebel, JM 2013. Differences in highly pathogenic avian influenza viral pathogenesis and associated early inflammatory response in chickens and ducks. Avian Pathology 42, 347364.
Fernando, RL and Garrick, DJ 2008. GenSel – user manual for a portfolio of genomic selection related analyses. Animal Breeding and Genetics, Iowa State University, Ames.
Gilmour, AR, Gogel, BJ, Cullis, BR, Welham, SJ and Thompson, R 2015. ASReml user guide release 4.1 structural specification. VSN International Ltd, UK.
Hui, KPY, Li, HS, Cheung, MC, Chan, RWY, Yuen, KM, Mok, CKP, Nicholls, JM, Peiris, JSM and Chan, MCW 2016. Highly pathogenic avian influenza H5N1 virus delays apoptotic responses via activation of STAT3. Scientific Reports 6, 28593.
Jamain, S, Quach, H, Betancur, C, Råstam, M, Colineaux, C, Gillberg, IC, Soderstrom, H, Giros, B, Leboyer, M, Gillberg, C and Bourgeron, T, Paris Autism Research International Sibpair Study 2003. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nature Genetics 34, 2729.
Karpala, AJ, Steward, C, McKay, J, Lowenthal, JW and Bean, AGD 2011. Characterization of chicken MDA5 activity: regulation of IFN-β in the absence of RIG-I functionality. Journal of Immunology 186, 53975405.
Kizilkaya, K, Tait, RG, Garrick, DJ, Fernando, RL and Reecy, JM 2013. Genome-wide association study of infectious bovine keratoconjunctivitis in Angus cattle. BMC Genetics 26, 1423.
Ko, JH, Jin, HK, Asano, A, Takada, A, Ninomiya, A, Kida, H, Hokiyama, H, Ohara, M, Tsuzuki, M, Nishibori, M, Mizutani, M and Watanabe, T 2002. Polymorphisms and the differential antiviral activity of the chicken Mx gene. Genome Research 12, 595601.
Kranis, A, Gheyas, AA, Boschiero, C, Turner, F, Yu, L, Smith, S, Talbot, R, Pirani, A, Brew, F, Kaiser, P, Hocking, PM, Fife, M, Salmon, N, Fulton, J, Strom, TM, Habrer, G, Weigend, S, Preisinger, R, Gholami, M, Quanbari, S, Simianer, H, Watson, KA, Woolliams, JA and Burt, DW 2013. Development of a high density 600K SNP genotyping array for chicken. BMC Genomics 14, 59.
Malerba, G and Pignatti, PF 2005. A review of asthma genetics: gene expression studies and recent candidates. Journal of Applied Genetics 46, 93104.
Matsuu, A, Kobayashi, T, Patchimasiri, T, Shiina, T, Suzuki, S, Chaichoune, K, Ratanakom, P, Hiromoto, Y, Abe, H, Parchariyanon, S and Saito, T 2016. Pathogencity of genetically similar, H5N1 highly pathogenic avian influenza virus strains in chicken and the differences in sensitivity among different chicken breeds. PLoS One 11, e0153649.
Meuwissen, THE, Hayes, BJ and Goddard, ME 2001. Prediction of total genetic value using genome-wide dense marker maps. Genetics 157, 18191829.
McCarthy, MI, Abecasis, GR, Cardon, LR, Goldstein, DB, Little, J, Ioannidis, JP and Hirschhorn, JN 2008. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nature Reviews Genetics 9, 356369.
Nurieva, RI, Chung, Y, Martinez, GJ, Yang, XO, Tanaka, S, Matskevitch, TD, Wang, YH and Dong, C 2009. Bcl6 mediates the development of T follicular helper cells. Science 325, 10011005.
Post, J, Burt, DW, Cornelissen, JB, Broks, V, van Zoelen, D and Peeters, B 2012. Systemic virus distribution and host responses in brain and intestine of chickens infected with low pathogenic or high pathogenic avian influenza virus. Virology Journal 9, 61.
Purcell, S, Neale, B, Todd-Brown, K, Thomas, L, Ferreira, MAR, Bender, D, Maller, J, Sklar, P, de Bakker, PIW, Daly, MJ and Sham, PC 2007. PLINK: a toolset for whole-genome association and population-based linkage analysis. American Journal of Human Genetics 81, 559575.
Ranaware, PB, Mishra, A, Vijayakumar, P, Gandhale, PN, Kumar, H, Kulkarni, DD and Raut, AA 2016. Genome wide host gene expression analysis in chicken lungs infected with avian influenza viruses. PLoS One 11, e0153671.
Ruiz-Hernandez, R, Mwangi, W, Peroval, M, Sadeyen, JR, Ascough, S, Balkissoon, D, Staines, K, Boyd, A, McCauley, J, Smith, A and Butter, C 2016. Host genetics determine susceptibility to avian influenza infection and transmission dynamics. Scientific Reports 6, 26787.
Sironi, L, Williams, JL, Moreno-Martin, AM, Ramelli, P, Stella, A, Jianlin, H, Weigend, S, Lombardi, G, Cordioli, P and Mariani, P 2008. Susceptibility of different chicken lines to H7N1 highly pathogenic avian influenza virus and the role of Mx gene polymorphism coding amino acid position 631. Virology 380, 152156.
Sironi, L, Williams, JL, Stella, A, Minozzi, G, Moreno, A, Ramelli, P, Han, J, Weigend, S, Wan, J, Lombardi, G, Cordioli, P and Mariani, P 2011. Genomic study of the response of chicken to highly pathogenic avian influenza virus. BMC Proceedings 5, 25.
Smith, J, Smith, N, Yu, L, Paton, IR, Gutowska, MW, Forrest, HL, Danner, AF, Seiler, JP, Digard, P, Webster, RG and Burt, DW 2015. A comparative analysis of host responses to avian influenza infection in ducks and chickens highlights a role for the interferon-induced transmembrane proteins in viral resistance. BMC Genomics 16, 574.
Villanueva, B, Fernández, J, Garcia-Cortês, LA, Varona, L, Daetwyler, HD and Toro, MA 2011. Accuracy of genomewide evaluation for disease resistance in aquaculture breeding programs. Journal of Animal Science 89, 34333442.
Wang, Y, Brahmakshatriya, V, Lupiani, B, Reddy, SM, Soibam, B, Benham, AL, Gunaratne, P, Liu, H, Trakooljul, N, Ing, N, Okimoto, R and Zhou, H 2012. Integrated analysis of microRNA expression and mRNA transcriptome in lungs of avian influenza virus infected broilers. BMC Genomics 13, 278.
Zhao, X, Onteru, S, Saatchi, M, Garrick, D and Rothschild, M 2013. A genome-wide association study for canine cryptorchidism in Siberian Huskies. Journal of Animal Breeding and Genetics 131, 202209.
Zou, W, Ke, J, Zhang, A, Zhou, M, Liao, Y, Zhu, J, Zhou, H, Tu, J, Chen, H and Jin, M 2010. Proteomics analysis of differential expression of chicken brain tissue proteins in response to neurovirulent H5N1 avian influenza virus infection. Journal of Proteome Research 9, 37893798.


Type Description Title
Supplementary materials

Drobik-Czwarno et al supplementary material 1
Drobik-Czwarno et al supplementary material

 Word (2.0 MB)
2.0 MB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed