Evidence for widespread epistatic interactions influencing Marek's disease virus viremia levels in chicken.

Marek's disease (MD), a T cell lymphoma induced by the Marek's disease virus (MDV), is the main chronic infectious disease concern threatening the poultry industry. Enhancing genetic resistance to MD in commercial poultry is an attractive method to augment MD vaccines, which is currently the control method of choice. In order to implement this control strategy through marker-assisted selection (MAS), it is necessary to identify quantitative trait loci (QTL) or genes that influence MD incidence. Previous studies have demonstrated that it is possible to identify QTL that confer MD resistance in both experimental and commercial chickens. With the advent of the chicken genome sequence and new genomic tools, and evidence that interactions are important in understanding complex traits, the line 6 x 7 F(2) experimental resource population was re-evaluated with finer resolution for epistatic interactions. The F(2) population, consisting of 272 individuals and previously genotyped with 133 genetic markers, was combined along with 576 additional single nucleotide polymorphisms (SNPs) genotyped on 80 individuals in each of the distribution tails for MD and other associated traits, and tested for the presence of main effects and two-way epistatic interactions accounting for MD incidence, viremia titers, and length of survival. Main effects were generally not significant but a large number of highly significant interactions, involving loci located throughout the genome, were identified that account for MDV viremia titers in infected birds. These results suggest that resistance to MD is highly complex and will require the incorporation of epistatic interaction analyses and functional genomic approaches to reveal the underlying genetic basis.