Integrative Genomics to Provide Basic and Applied Knowledge to Control Marek's Disease in Chicken

Marek’s disease (MD) is a T cell lymphoma disease of chickens induced by the Marek’s disease virus (MDV). Selecting for increased genetic resistance is a control strategy that can augment existing MD vaccinal protection. Like other traits, this goal is very difficult to achieve even with modern efforts (e.g., GWAS) as the genetic markers identified usually define LD blocks with either no or several genes.

Gene expression is a major factor accounting for phenotypic variation. Taking advantage of allele-specific expression (ASE) screens, we identified SNPs in specific genes using experimental layers. Analysis of an MD resource population genotyped with a custom SNP arrays yields a h² of 0.53 for MD genetic resistance while ASE SNPs alone account for 83+% of the genetic variance. This result supports the importance of transcriptional regulation on genetic resistance to MD and the infinitesimal model. 

To validate the association of ASE SNPs with MD genetic resistance, sires were genotyped, BLUP EBVs based on SNPs and pedigree calculated, and bidirectionally selected based on the SNP EBVs. Progeny tests demonstrate that after only one generation of selection, there was greater than 20% difference in MD incidence. Compared to pedigree, genomic selection on ASE SNPs was 61% higher.

We conclude that ASE SNPs are functionally linked to causative polymorphisms that alter transcriptional levels in genes that manifest the changes in disease incidence, thus, showing variation in cis-regulatory elements is the major mechanism that accounts for variation in MD genetic resistance between these two experimental lines.