Quantitative trait loci and transcriptome signatures associated with avian heritable resistance to Campylobacter

Androniki Psifidi,David A Hume,Georgios Banos,Pete Kaiser,Andreas Kranis,Jim Kaufman,Paul M Hocking,Kay Russell,Kellie A Watson,Stephen J Bush,Mark Fife,Santiago Avendano,Richard A Bailey,Lisa M Rothwell,Diego Robledo,Mark P Stevens,Abi Bremner

doi:10.1038/s41598-020-79005-7

Abstract

Campylobacter is the leading cause of bacterial foodborne gastroenteritis worldwide. Handling or consumption of contaminated poultry meat is a key risk factor for human campylobacteriosis. One potential control strategy is to select poultry with increased resistance to Campylobacter. We associated high-density genome-wide genotypes (600K single nucleotide polymorphisms) of 3000 commercial broilers with Campylobacter load in their caeca. Trait heritability was modest but significant (h2 = 0.11 ± 0.03). Results confirmed quantitative trait loci (QTL) on chromosomes 14 and 16 previously identified in inbred chicken lines, and detected two additional QTLs on chromosomes 19 and 26. RNA-Seq analysis of broilers at the extremes of colonisation phenotype identified differentially transcribed genes within the QTL on chromosome 16 and proximal to the major histocompatibility complex (MHC) locus. We identified strong cis-QTLs located within MHC suggesting the presence of cis-acting variation in MHC class I and II and BG genes. Pathway and network analyses implicated cooperative functional pathways and networks in colonisation, including those related to antigen presentation, innate and adaptive immune responses, calcium, and renin–angiotensin signalling. While co-selection for enhanced resistance and other breeding goals is feasible, the frequency of resistance-associated alleles was high in the population studied and non-genetic factors significantly influenced Campylobacter colonisation.

Highlights

Campylobacter is the leading cause of bacterial foodborne gastroenteritis worldwide
In other studies, where Campylobacter inoculation was via natural exposure mimicking field exposure, there was no association between Campylobacter levels and bird growth r ate[25] or gut p athology[26], and selection for Campylobacter resistance remained compatible with other breeding goals[26]
A previously published genome-wide association study (GWAS) on C. jejuni intestinal colonisation, where phenotypes were analysed as a binary trait in a novel dual-purpose chicken breed, revealed a resistance-associated locus on chromosome 11 near the CDH13 gene encoding T-cadherin, and a second candidate locus on chromosome 5 was identified close to calmodulin (CALM1), a calcium-activated modulator of cadherin function[17]

Summary

Introduction

Campylobacter is the leading cause of bacterial foodborne gastroenteritis worldwide. Handling or consumption of contaminated poultry meat is a key risk factor for human campylobacteriosis. A previously published genome-wide association study (GWAS) on C. jejuni intestinal colonisation, where phenotypes were analysed as a binary trait in a novel dual-purpose chicken breed, revealed a resistance-associated locus on chromosome 11 near the CDH13 gene encoding T-cadherin, and a second candidate locus on chromosome 5 was identified close to calmodulin (CALM1), a calcium-activated modulator of cadherin function[17]. Both genes differed in relative expression in a manner associated with r esistance[17]. Analysis of caecal gene expression in chicken lines of varying susceptibility to Campylobacter colonisation has identified transcriptional signatures associated with differential resistance, including genes influencing the immune r esponse[13,14,15,16]

Methods

Results

Discussion

Conclusion