# Genetic variation associated with Marek’s disease resistance and susceptibility in white leghorn chickens

## TL;DR

This study identifies genetic variations and immune pathways linked to resistance and susceptibility to Marek’s disease in chickens, offering insights for improving poultry health.

## Contribution

The study reveals novel immune signaling pathways and genetic factors associated with Marek’s disease resistance and susceptibility in chickens.

## Key findings

- The WNT/SHH Axonal Guidance Signaling Pathway is enriched in both MD-susceptible and resistant chicken lines.
- The ISG15 antiviral mechanism and HIPPO signaling pathways are enriched in MD-resistant chickens.
- Thyroid cancer signaling and JAK/STAT pathways are significantly enriched in MD-resistant line 6 chickens.

## Abstract

Despite of effective control by vaccination, Marek’s disease virus (MDV) remains a significant threat to poultry health and productivity due to continued virus evolution, which drives the need to better understand host genetic factors underlying the resistance and susceptibility. Although great efforts have been made toward understanding the genetic resistance to MD, the genetic variations underlying varied susceptibility to MD remains poorly understood. In this study, we conducted a comprehensive genome-wide association and pathway enrichment analysis in chicken genomes of a MD-resistant inbred line 6 (LN6), a MD-susceptible inbred line 7 (SUS), and 6 recombinant congenic strains (RCS) derived from the lines 6 and 7. The incidence of MD in the RCS varied significantly, ranging from RCS-J – 0%, RCS-D – 4%, line 6 – 6%, RCS-F – 10%, RCS-W – 15%, RCS-K – 24%, to RCS-M – 41%. The progenital line 7 was observed with a 97% incidence in response to infection with a very virulent plus MDV strain (648A). Three models were constructed: GWASLN6 with the line 6 birds contrasted against the remaining birds, GWASSUS with the line 7 birds contrasted against the remaining birds, and GWASRES-JD6 with group of RCS-J, RCS-D and line 6 together contrasted against the remaining birds. Our results revealed distinct enrichment patterns: while WNT/SHH Axonal Guidance Signaling Pathway is enriched in both GWASSUS and GWASRES-JD6, the Th2 pathway, Th1/Th2 Activation Pathway, and the interleukin (IL)-33 were predominant in GWASSUS. On the other hand, the ISG15 antiviral mechanism and HIPPO signalling pathways were enriched in the GWASRES-JD6. In contrast, thyroid cancer signalling, CXCR4, ILK, IL-8, IL-3, JAK/STAT and mTOR signalling pathways were significantly enriched in GWASLN6. These findings underscore the complex interplay of immune signalling, host-pathogen interactions, and genetic regulation in shaping MD resistance. Key pathways and candidate genes identified in this study provide valuable targets for further functional validation and may inform future genetic selection and new vaccine strategies to enhance MD resistance in poultry.