Genomics Helps Scientist and Producers Understand and Manage Emerging Disease

Genomics Helps Scientist and Producers Understand and Manage Emerging Disease

Brittle bone disease, or osteogenesis imperfecta, is a detrimental disorder in livestock.  Calves with the condition commonly suffer multiple bone fractures in utero or at delivery, and if able to stand, have lax tendons.  Depending on the cause, calves may also have blue coloration in what is otherwise the white of the eye and soft teeth. Osteogenesis imperfecta (OI) occurs in many species where it is more highly studied.  In most cases, it is attributed to a new genetic mutation that occurred in the affected individual. 

Early last year, the Red Angus Association contacted Dr. David Steffen at UNL’s, Nebraska Veterinary Diagnostic Center (NVDC), reporting a bull calf with symptoms suggestive of OI.  The calf was delivered to the NVDC where the phenotype was confirmed. This case was notable as the sire of the affected calf had sired another calf confirmed to have OI the previous year.  Further, a small number of other suspect cases were verbally reported associated with the wide use of the bull. Working with the Red Angus Association, it was verified that the sire and dam of the bull calf shared 4 ancestors within three generations.  Considering the occurrence of the condition in two calves sired by the same bull, the relationship between the bull and dam of one affected calf, and the usual low frequency of the defect,  it became of concern that OI in these calves could be due to a recessive mutation carried by the bull and the cows.  If this were the case, identification of the mutation would be important so carriers could be identified by genetic testing prior to breeding to eliminate the risk of producing affected calves.

DNA samples from the affected calves, the sire, and the dam of the bull calf were sequenced.  Analysis by UNL Animal Science researcher, Dr. Jessica Petersen, revealed a genetic mutation present in each of the calves in an important part of a collagen gene critical to the formation of bone and cartilage.  While the bull did not have this mutation in DNA isolated from his blood, the mutation was found in a small proportion (4.5%) of the cells in his semen.   The investigators hypothesize that the mutation occurred in the cells of the bull’s developing testicle while he was in utero.  This finding means the bull produced two types of semen – a majority of the semen was normal, while a small portion carried the mutation associated with osteogenesis imperfecta.  The affected calves were simply unlucky as they were each derived from one of the estimated 4.5% of the sperm cells with the deleterious mutation. 

The identification of this novel mutation was possible due to the producers’ careful recording and reporting of abnormal calves to the breed association.  The submission of samples for diagnostic analysis and support of the American Red Angus Association was crucial to understanding the problem.  This successful outcome demonstrates how genomic tools are efficiently employed to help understand emerging conditions, and how they can allow for rapid action to limit losses.  Importantly to the breed, the data indicate the condition is not being carried as a hidden recessive in offspring of the sire or in other related individuals. While this particular bull has been culled, continued use would have meant a low risk of abnormal calves; all normal calves he produced did not inherit the mutation and therefore are clear with respect to OI.  

The analyses performed in this study are outlined in the publication Evidence for a de novo, dominant germ-line mutation causative of osteogenesis imperfecta in two Red Angus calves in the journal, "Mammalian Genome."


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