Genomic Tools for the Identification of Loci Associated with Facial Eczema in New Zealand Sheep.

Kathryn M Mcrae,Matthew J Bixley,John C Mcewan,Suzanne J Rowe,Jeffrey E Plowman,Sheryl-Anne N Newman,Patricia L Johnson,Neil G Cullen,Hayley J Baird,Santanu Deb-Choudhury,Neville C Amyes,Shannon M Clarke,Ken G Dodds,Rudiger Brauning

doi:10.3390/genes12101560

Abstract

Facial eczema (FE) is a significant metabolic disease that affects New Zealand ruminants. Ingestion of the mycotoxin sporidesmin leads to liver and bile duct damage, which can result in photosensitisation, reduced productivity and death. Strategies used to manage the incidence and severity of the disease include breeding. In sheep, there is considerable genetic variation in the response to FE. A commercial testing program is available for ram breeders who aim to increase tolerance, determined by the concentration of the serum enzyme, gamma-glutamyltransferase 21 days after a measured sporidesmin challenge (GGT21). Genome-wide association studies were carried out to determine regions of the genome associated with GGT21. Two regions on chromosomes 15 and 24 are reported, which explain 5% and 1% of the phenotypic variance in the response to FE, respectively. The region on chromosome 15 contains the β-globin locus. Of the significant SNPs in the region, one is a missense variant within the haemoglobin subunit β (HBB) gene. Mass spectrometry of haemoglobin from animals with differing genotypes at this locus indicated that genotypes are associated with different forms of adult β-globin. Haemoglobin haplotypes have previously been associated with variation in several health-related traits in sheep and warrant further investigation regarding their role in tolerance to FE in sheep. We show a strategic approach to the identification of regions of importance for commercial breeding programs with a combination of discovery, statistical and biological validation. This study highlights the power of using increased density genotyping for the identification of influential genomic regions, combined with subsequent inclusion on lower density genotyping platforms.

Highlights

To investigate regions of the genome that are associated with Facial eczema (FE), imputed HD genotype data were combined with log-transformed serum GGT levels at 21 days after a measured sporidesmin challenge (GGT21) for additive genome-wide association studies (GWAS) analysis (Figures 1A,B and S1)
Our results indicate that the β-globin locus haplotype, and ovine haemoglobin type, can be estimated using SNPs within the β-globin locus, one animal that was hypothesised to be homozygous for haplotype B appeared to have a shortened form of the βA -globin peptide
Two loci for tolerance to facial eczema in sheep are reported on chromosomes 15 and 24

Summary

Introduction

Facial eczema (FE) is a metabolic disease of major welfare concern and economic loss to farmers in New Zealand. The disease is caused by ingestion of the mycotoxin sporidesmin, which is found in the spores of the fungus Pseudopithomyces chartarum (formerly Pithomyces chartarum) [1,2]. Pse. chartarum grows on the dead leaf matter at the base of pastures, and ingestion of the toxic fungal spores by ruminants leads to liver inflammation and bile duct blockage [3]. Animals might show no clinical signs of disease [4], production losses arise from a decrease in production [5] and lowered reproduction [6,7,8]

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