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 α-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 Major Histocompatability Complex (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 quantitative trait locus 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 eight pure lines of elite egg-layer birds. Thirty-eight QTLR were found on 19 chicken chromosomes. Candidate genes, microRNAs, long non-coding RNAs and potentially functional mutations were identified in these regions. Association tests were carried out in 26 of the QTLR, using eight 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 a 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.
Highlights
Marek’s disease (MD) represents a significant global economic and animal welfare issue.This immunosuppressive disease is responsible for an estimated 2 billion USD annual economicGenes 2020, 11, 1019; doi:10.3390/genes11091019 www.mdpi.com/journal/genesGenes 2020, 11, 1019 loss to the global poultry industry [1], through bird mortality, lost egg production, and vaccination costs
If birds do not succumb to Marek’s disease virus (MDV) itself, they are often left severely compromised with secondary infections such as Escherichia coli (E. coli) [3]
N1, the estimated number of falsified null hypotheses at proportion of false positives (PFP) ≤ 0.2 [39,40], ranged from 1718 in Family 1 (0.7% of all markers tested in the family) to 17,385 in Family 2 (6.7% of markers tested), indicating the actual presence of true quantitative trait locus (QTL) effects
Summary
Marek’s disease (MD) represents a significant global economic and animal welfare issue.This immunosuppressive disease is responsible for an estimated 2 billion USD annual economicGenes 2020, 11, 1019; doi:10.3390/genes11091019 www.mdpi.com/journal/genesGenes 2020, 11, 1019 loss to the global poultry industry [1], through bird mortality, lost egg production, and vaccination costs. Marek’s disease (MD) represents a significant global economic and animal welfare issue. This immunosuppressive disease is responsible for an estimated 2 billion USD annual economic. The virus responsible, Marek’s disease virus (MDV), is an α-herpes virus that initially infects. The commercially utilized vaccines are not sterilizing vaccines They prevent the formation of tumours, but do not prevent infection by MDV or shedding of the pathogenic virus [4]. Both vaccine and pathogenic MDVs are found in vaccinated flocks, resulting in the emergence of increasingly more virulent strains [5]
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