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

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.