Mapping QTL associated with resistance to avian oncogenic Marek’s Disease Virus (MDV) reveals major candidate genes and variants

Jacqueline Smith, Ehud Lipkin , Morris Soller, Janet E Fulton, David Burt

Research output: Contribution to journalArticlepeer-review

Abstract

Marek’s Disease (MD) represents a significant global economic and animal welfare issue. Marek’s Disease Virus (MDV) is a highly contagious oncogenic and highly immune-suppressive alpha-herpes virus, which infects chickens, causing neurological effects and tumour formation. Though partially controlled by vaccination, MD continues to have a profound impact on animal health and on the poultry industry. Genetic selection provides an alternative and complementary method to vaccination. However, even after years of study, the genetic mechanisms underlying resistance to MDV remain poorly understood. The MHC is known to play a role in disease resistance, along with a handful of other non-MHC genes. In this study, one of the largest to date, we used a multi-facetted approach to identify QTL regions (QTLR) influencing resistance to MDV, including an F6 population from a full-sib advanced intercross line (FSIL) between two elite commercial layer lines differing in resistance to MDV, RNA-seq information from virus challenged chicks, and genome wide association study (GWAS) from multiple commercial lines. Candidate genomic elements residing in the QTLR were further tested for association with offspring mortality in the face of MDV challenge in 8 pure lines of elite egg-layer birds. Thirty-eight QTLR were found on 19 chicken chromosomes. Candidate genes, miRNAs, lncRNAs and potentially functional mutations were identified in these regions. Association tests were carried out in 26 of the QTLR, using 8 pure lines of elite egg-layer birds. Numerous candidate genomic elements were strongly associated with MD resistance. Genomic regions significantly associated with resistance to MDV were mapped, and candidate genes identified. Various QTLR elements were shown to have strong genetic association with resistance. These results provide a large number of significant targets for mitigating the effects of MDV infection on both poultry health and the economy – whether by means of selective breeding, improved vaccine design or gene-editing technologies.
Original languageEnglish
Article number1019
Number of pages21
JournalGenes
Volume11
Early online date30 Aug 2020
DOIs
Publication statusE-pub ahead of print - 30 Aug 2020

Keywords

  • Marek’s Disease Virus
  • QTL
  • GWAS
  • transcriptomics
  • FSIL
  • disease resistance
  • candidate gene

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