Aussie said:
Has any one heard of a new genetic defect in Angus ? It is rumored over here there is a few bulls that are throwing calves with a fifth leg from the shoulder that have turned up lately
Yes - Dr Laurie Denholm is investigating it
This from the New South Wales Animal Health Surveillance Newsletter July-Sept 2011
Extra legs in Angus calves Polymelia is the condition of being born with one or more extra limbs. If the limb or limbs are attached to the vertebral column, this is called notomelia. The incidence of notomelia seems to be increasing in Angus calves in Australia above the sporadic background level, suggesting the possibility of an emerging heritable defect in this breed. At least 15 cases of notomelia have been reported in newborn Angus calves in NSW in the last 2 years. One purebred commercial Angus herd withan increased incidence of other genetic disorders from line breeding (i.e. mating animals that are closely related genetically, in this case animals with a propensity for high fat marbling in muscle) has also experienced several cases of notomelia in each of the last two calving seasons. The clustering of notomelia cases in this linebred herd suggests the possibility of an underlying heritable cause for notomelia in Angus calves. NSW veterinarians who see polymelia cases in Angus calves should contact their local LHPA veterinarian or Dr Laurence Denholm of the NSW Department of Primary Industries and encourage the owners to participate in finding the cause. Trial breeding can identify patterns of inheritance, and Dr Denholm is seeking further polymelia cases – particularly affected Angus heifer calves – to interbreed to determine the heritability of this congenital defect. Laboratory analysis of the DNA of these calves is also likely to reveal any genetic changes associated with this condition.Samples from affected calves have been sent to a laboratory in the USA to look for any changes in their DNA compared with the DNA of calves without the condition. The laboratory, however, needs additional DNA samples from cases of polymelia to make progress in this research. The aim is to develop a diagnostic DNA test to detectcarriers. The test can then be used to prevent further spread of the defect, as has been achieved with other genetic defects in recent years.
Variants of polymelia are classified according to the point of attachment to the body: notomelia where the attachment is in the region of the embryonic notochord; cephalomelia where the attachment is on the head; thoracomelia where the attachment is on the thorax below the dorsal midline; and dipygus or pygomelia where the attachment is to the pelvis. The majority of bovine polymelia cases are notomelic.The foot of the supernumerary limb may be normal or the digits may be fused (syndactyly). Minor bone abnormalities in these extra limbs are also common, including fusion of the bones at the shoulder and elbow. Thin bands of muscle may or may not be seen embedded in abnormally large amounts of fat on dissection of the limb. Some of the calves have more than one, and up to four, complete supernumerary limbs; others have a single additional limb but with abnormal bifurcations at a level below the shoulder joint, sometimes creating the appearance of multiple limbs. The economic effects of the polymelia condition are related to the management of difficult births and the cost of surgery to remove the extra limbs. In many polymelia cases the additional limbs interfere with birth of the affected calf, leading to death of the calf and even death of the mother cow. After birth, in some cases the supernumerary limbs remain small and the affected calves appear to grow and breed normally, regardless of whether or not the extra limbs are surgically removed. In other cases the supernumerary limbs grow in proportion to the animal and become quite large, interfering with walking and with normal life – a significant animal welfare issue. Developmental anomalies of the limbs are among the most common congenital defects in humans and domestic animals and are more frequent in the lower limbs. The subcellular molecular processes in the developing embryo that lead to polymelia are, however, not well understood at this time. True polymelia apparently results from a failure in the normal regression of the supernumerary primordial limb buds in the mesodermal layer of the developing embryo; hence one or more supernumerary limbs (or parts of limbs) arise from continued development of these persistent vestigial limb buds. Normally, the supernumerary limb buds regress early in embryonic development from localised intercellular signals that stop expression of the genes required for further limb growth, but this seems to fail in the case of polymelia. In Drosophila flies, mutations of the slimb gene are known to cause supernumerary limbs because the gene loses its capacity to regulate the transcription of genes involved in local control of the cell cycle in cells of the supernumerary limb buds. This control is needed for the normal cessation of further cell growth and replication and hence for further development in the supernumerary limb buds.
A similar gene known as the β-TrCP gene exists in mammals, but its functions in mammalian embryonic development are currently unknown. However, there is some evidence of β-TrCP involvement in biochemical pathways similar to those of slimb that regulate the cell cycle – and hence cell replication – to effectively inhibit further cellular development at specific locations, including in the supernumerary limb buds. It may be that mutation of this β-TrCP gene, or another related gene in the same embryonic biochemical pathway, blocks the normal local controls on cell development and replication in the calf’s supernumerary limb buds – i.e. the controls that prevent polymelia from developing in normal calves. Despite the evidence for a heritable basis to polymelia in Angus cattle, alternative causes are possible but do seem unlikely on epidemiological grounds, particularly given the apparent breed predisposition and the wide geographic distribution of these recent polymelia cases. For example, tadpoles of several frog species develop extra legs when infected with parasitic species of the trematode Riberoia, particularly when the tadpoles have also been exposed to environmental toxins such as organochlorine pesticides. Vitamin A toxicity also causes supernumerary hind limbs to develop in frogs. The toxicity and the parasitic infection may simply interfere with the same intercellular signalling pathway in early embryonic development and thereby produce the same developmental abnormality as is seen with a heritable mutation of one of the genes involved in this signalling pathway. By affecting the same developmental pathway, quite different environmental factors and genetic mutations can produce an identical developmental defect such as polymelia.
The NSW contributors to this project are Dr Laurence Denholm (NSW DPI), Lisa Martin (New England Livestock Health and Pest Authority), Andrew Denman (Blayney Veterinary Hospital) and Professor Peter Windsor (University of Sydney).
The collaborating genomics laboratory in the USA is led by Associate Professor Jonathan Beever of the University of Illinois and AgriGenomics Inc. His laboratory has identified the mutations in the genes that code for many heritable defects in cattle, including the mutation that causes congenital ‘curly calf’ syndrome in Angus cattle (arthrogryposis multiplex), which was reported in Animal Health Surveillance 2008/3.
For further information contact Dr
Laurence Denholm, NSW DPI Orange,
on (02) 63655482, or lauriedenholm@
industry.nsw.gov.au.