A matter of life and death; identifying host genomic factors that determine susceptibility of chickens to highly pathogenic avian influenza

DNA samples collected from survivors of recent outbreaks of highly pathogenic avian influenza (HPAI) in Mexico and the USA have provided a rare opportunity to study the genetic mechanisms underpinning susceptibility of chickens to this devastating and economically impactful disease which normally exhibits 70-100% mortality in the chicken host. Whole Genome Sequence (WGS) data has been used to perform Genome-Wide Association Studies (GWAS), which have highlighted single nucleotide polymorphisms (SNPs) segregating significantly between survivors and controls, with a pedigreed experimental group exhibiting a highly significant signal on chicken chromosome 2 in the region of a biologically relevant gene. Candidate SNPs for resilience are currently being validated using in vitro gene editing methodologiesthat modulate candidate gene expression to investigate the effect on viral replication and cellular response to HPAI infection. A detailed understanding of the genomic resilience to HPAI from this study will have implications for both the poultry industry and for public health.