Molecular characterisation of ichthyosis fetalis and Niemann-pick type C disease in cattle and brachygnathia, cardiomegaly and renal hypoplasia syndrome and pulmonary hypoplasia with anasarca in sheep

Abstract

Since the domestication of cattle and sheep, these species have been extensively farmed to produce food and fibre for human consumption and use. The move from natural breeding to selective breeding has enabled for desired production traits to be selected, and has facilitated accelerated genetic gain within these populations. The presence of deleterious alleles is not a new phenomenon in animal breeding, yet inherited diseases continue to impact animal welfare, productivity and profitability. The advancement in molecular genetics, sequencing technologies and bioinformatics over the past few decades has facilitated the wide generation of genomes for cattle and sheep, and has allowed for improved variant discovery. Despite these advances, reporting of inherited diseases in cattle and sheep is not commonplace in Australia. This thesis utilised several approaches that included SNP genotyping, Sanger sequencing, candidate gene analysis and whole genome sequencing for initially ten inherited diseases, to identify causal mutations. These approaches were used successfully for four inherited diseases: ichthyosis fetalis in Shorthorn cattle, Niemann-Pick type C disease in Angus/Angus-cross cattle, brachygnathia, cardiomegaly and renal hypoplasia syndrome in Merino sheep and pulmonary hypoplasia with anasarca in Persian sheep, which forms the basis of this thesis. Diagnostic DNA tests were developed for these four diseases, and were used to improve breeding management. The communication of the results from this thesis will help provide awareness of emerging inherited diseases in Australian livestock populations, as well as highlighting the importance of taking a proactive approach for reporting and managing inherited diseases in livestock.