Challenges in the investigation of eight inherited diseases in ruminants-An Australian perspective

• Published in: Journal of animal science 2016-09, Vol.94, p.173-173
• Main Authors: Tammen, I, Woolley, S A, Tsimnadis, E R, Nowak, N, Tulloch, R L, Khatkar, M S, O'Rourke, B A
• Format: Article
• Language: English
• Subjects: Albinism; Alleles; Animal breeding; Animal care; Animal welfare; Arachnodactyly; Blindness; Bovidae; Calves; Cardiomyopathy; Cattle; Diseases; Drought; Gene mapping; Gene sequencing; Genetic disorders; Hereditary diseases; Heredity; Homozygosity; Hypoplasia; Ichthyosis; Inbreeding; Mandible; Mapping; Mutation; Niemann-Pick disease; Npc1 protein; Ovis aries; Pedigree; Phenotypes; Sheep; Vertebrae
• ISSN: 0021-8812; 1525-3163

Modern animal breeding technologies have accelerated the genetic gain in cattle and sheep for many desirable traits. However, at times this has resulted in decreases in effective population sizes and elevated rates of inbreeding, which can increase the risk of deleterious recessive alleles to be observed in homozygous form; as well as an increased risk for deleterious alleles to be dispersed widely Tins can manifest in an increased occurrence of inherited diseases, leading to production losses and animal welfare concerns. We have investigated eight diseases with a predicted recessive mode of inheritance in Australian sheep and cattle using 80 k SNPchip based homozygosity mapping and/or candidate gene analysis, with the ultimate aim to identify disease causing genes and mutations. We confirmed that the mutation known to cause congenital contrac-tural arachnodactyly in Angus cattle caused several cases of congenital contractural arachnodactyly in Murray Gray cattle. Congenital mandibular prognathia has been reported in several Droughtmaster cattle, and was mapped to a 3.1 MB region on BTA26. A positional candidate gene has been partially sequenced. Homozygosity mapping analysis for two suspected cases of Niemann-Pick disease in Angus cattle identified a region of homozygosity on BTA24 that contains the candidate gene NPC1. Sequencing identified a possible causative mutation which is currently being validated. Incomplete sequencing of the bovine candidate gene for pulmonary hypoplasia with anasarca in Persian sheep has so far not identified a disease associated mutation. Two suspected cases of cardiomyopathy and woolly haircoat syndrome in Poll Hereford calves tested negative for the mutation in PPP1R13L known to cause this disease in this breed. Partial sequencing of the gene did not identify a disease-causing mutation and homozygosity mapping revealed that neither animal was homozygous in the region of the candidate gene. The mutation in ABCA12 known to cause congenital ichthyosis in Chianina cattle was excluded as the disease causing mutation in a single Hereford calf that presented with ichthyosis. Homozygosity mapping confirmed ABCA12 as a strong candidate gene. Homozygosity mapping for congenital blindness or oculocutaneous albinism in two White Shorthorn cattle identified four regions of interest for further analysis. Samples for cervicothoracic vertebral sublaxation in Merino sheep have been collected and are awaiting homozygosity mapping. Despite lim