GENETIC DEFECTS - QUESTION and ANSWER
AA has endeavored to be transparent in managing genetic conditions, supplying industry with the best information available at that point in time. This page contains discussion on some commonly asked questions.
If you have any other questions on genetic conditions and how to manage or would like to contribute to any of the following discussions please email Carel Teseling.
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I have sold a lot of bulls that are potentially carrying the AM gene. I feel an obligation to contact clients about this and am currently drafting a letter, but unsure of what I should include in this letter.
I am wondering how other stud breeders are handling the issue of contacting clients that have purchased bulls which potentially carry the AM gene?
Paul Murray, Wagga Wagga
Answer:
Some members will not advise any of their previous bull buyers. It will depend on the breeder and their relationship with the bull buyer. They may not worry about phoning a bull buyer that only bought one bull from him in the past 5 years where the bull only has a 10% probability of being a carrier at this stage. However if they sold 10 bulls to a bull buyer and 5 of them have a 10% probability they may phone or visit the buyer and discuss the situation with them. The key objective is to make sure the bull buyer is informed of the status of the bulls and understands the practical implications of that.
Topic 2 - Explaining AM and NH to Bull Buyers:
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Bull sale season is approaching. I am concerned that they may not be well informed about AM/NH and this may affect the sale of all animals with any bloodlines known to have AM/NH.
Answer:
A two page article about AM and NH, written for commercial bull buyers is now available. DOWNLOAD A COPY HERE...A one page explanation of genetic recessive conditions has also been developed for sale catalogues. DOWNLOAD A COPY HERE...
(26/08/09)
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What is Fawn Calf Syndrome?
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What does an animal with Fawn Calf Syndrome look like?
Answer:
Care needs to be taken to not confuse AM with another genetic syndrome in newborn Angus calves, “fawn calf syndrome’ (FCS). Calves affected with FCS usually have less severe contractures of the spine and limb joints. Within a few months these abnormalities dissipate, so long as the affected calf is able to get up and suckle. FCS is characterised by distal (away from the body) joint over-extensibility at birth despite proximal (towards centre of body) joint contractures. Poor muscling (low muscle score) persists to maturity. Weak foot conformation also persists in adults.View a NSW DPI video with a text description of FCS.
Angus bloodlines identified as affected by AM are different from bloodlines proven to be carriers of FCS in a NSW Department of Primary Industries breeding trial.
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Will Fawn Calf Syndrome animals be handled the same as AM and NH animals?
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Will registration certificates and animal details page in the Angus Australia web-database display the FCS status of registered animals?
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Will the industry be notified of FCS carriers soon?
Answer:
FCS is also thought to be a recessive heritable defect. Once we have a DNA test we plan to handle Fawn Calf Syndrome in exactly the same way as AM and NH.Unfortunately, at this stage, we only have reports on about 30 animals that have produced FCS syndrome progeny. The benefit we had with the AM test results was that we had results for more than 300 animals with the vast majority free of the genetic defect. We could do a probability analysis for Fawn Calf Syndrome but because we don't have a test yet, publishing this information would not really be beneficial. In the absence of a DNA test we lack the ability to identify the 50% of the population that is free of the genetic condition. Another very important consideration is that we expect the frequency of FCS carrier animals in the Angus population (seedstock and commercial) to be a lot less than AM.
Bulls that have been identified as confirmed FCS carriers in the research trial (ET program with parent verification) Angus Australia carried out at Elizabeth Macarthur Agricultural Insitute include Bando 598 and Rambo 465T of JRS.
(26/08/2009)
Topic 4 - Reporting of Unusual Calves:
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What do I do if I find a defect calf on my property?
Answer:
The easiest way to collect blood from a dead calf, is to get it out of the heart using a needle. It is preferable to put the blood into an EDTA tube and a serum tube. We suggest getting some of these from your local vet. If you don't have any of these tubes then another option is a clean, heat sterilised bottleIf you are in South Australia Dr. Mary Carr is interested in getting reports of calves born with any defect.
26/08/09
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Every now and again I have been getting an otherwise normal blind calf. Are there any known blindness genetic defects in cattle?
Answer:
According to the Online Mendelian Inheritance in Animals Website a blindness genetic defect has been confirmed in seven species. Cattle is not one of the confirmed species. However this is no guarantee that genetic blindess in cattle does not exist.
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How many AM calves have been reported?
Answer:
The incidence of affected calves is very low. 25 calves have been reported to AA as AM affected. 10 of these have been confirmed through DNA testing. Dr. Laurie Denholm, NSW DPI, was AWARE of 50 - 60 cases in Australia early December. He has done post mortems on 7 and has collected photos and data on 20. Most breeders are cautious about close inbreeding and there are not many cattle in the current Angus population where animals with AM bloodlines occur on both sides of the pedigree. Since breeders became aware of the conditions, and accurate diagnostic tests became available, affected calves can be avoided through careful breeding management. In several incidences where known matings between carrier animals have been carefully monitored (both in Australia and in USA) the number of affected calves has approximated the expectation of 25% affected calves.The reason why the number of AM affected animals is very low in the field can be understood when we look at some joining case studies.
Consider a herd of commercial 100 cows. They are from a multi-sire mating of their dams to sons of bull X. Bull X is a carrier of AM (i). Therefore of these 100 cows, 50 % of them are expected to be sired by an an AM carrier bull as it’s expected that 50 % of the sons of bull X (ii) will have inherited the AM gene. Of the 50 % that are sired by an AM carrier bull, only 50 % of them are expected to inherit the AM gene. Therefore of the 100 cows (iii) only 25 of them are expected to carry the AM gene.
Next the producer joins their 100 cows (iii) to sons of bull X (ii). In other words they are joining grand daughters of bull X to sons of bull X. So we are talking about some pretty extreme linebreeding for a commercial producer. We expect that only 25 of the 100 cows carry the AM gene. And we expect only half the bulls they are being joined to will carry the AM gene. So only 12.5 % of the matings are expected to be between AM carriers. Of these 12.5 calves, only a quarter of them (3.125) are expected to inherit a copy of the AM gene from both parents and therefore be AM affected (v) or born dead.
A more likely scenario would be that the 100 cows (iii) are joined to grand sons of bull X, so we have cousin matings. We would then expect calf losses to AM to be 1.5625 per 100 (vi)
But the even more likely scenario is that most commercial breeders are conscious not to mate animals with similar bloodlines, so the incidence of AM is much lower than 1.5625 per 100.
Bull X (AMC)
(i)Sons of Bull X
(ii)Daughter of
son of Bull X
(ii)100 Daughters
of sons of Bull X
(granddaugters of Bull X)
(iv)Calves from
joining 100
granddaughters
of Bull X (iv) to
sons of
Bull X (ii)
(v)Calves from
joining 100
granddaughters
of Bull X (iv)
to grand
sons of Bull X
(vi)% probability of carrying the AM gene100%50%25%% of animals in mob expected to carry the AM gene25%%r of carrier to carrier matings12.5%% of AM affected animals3.125%1.5625%
(26/08/2009)
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How many animals are carrying or likely to be carrying the AM gene?
Answer:
12.5 % of animals on the Angus database are either AM carriers (AMC) or have a probability between 1 and 99% of being carriers.
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What is the average probability of a registered Angus animal being an AM carrier?
Answer:
The mean probability of an Angus animal being a carrier is very close to 1.
(26/08/2009)
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How many NH calves have been reported?
Answer:
4 calves have been reported to AA as NH affected. It is thought that a significant percentage of mortalities relating to NH occur through embryonic or fetal loss during gestation. This may cause the condition to be misdiagnosed or go unnoticed.
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How many animals are carrying or likely to be carrying the NH gene
Answer:
Approximately 12.5 % of animals on the Angus database are either NH carriers (NHC) or have a probability between 1 and 99% of being carriers.
Topic 7 - DNA Testing For AM and NH:
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I have already sent in samples for DNA profiling/ parent verification for an animal. Is that test able to be re-used for the AM or NH tests or do new semen, blood or hair samples have to be provided?
Answer:
The ability to use these samples for AM or NH testing will depend on the quality/quantity of the sample previously submitted. Angus Australia (AA) can’t guarantee the suitability of these samples for DNA extraction and analysis and would therefore recommend, if the animal is still available, you supply another sample for those animals.For example if you have supplied a hair sample that was used to obtain the DNA profile AA might be able to find the sample in our archives and submit a sub-sample for AM or NH testing. If you are asking this question because the animal is dead or sold and you have access to semen it might be worth your while to supply us with a thawed straw of semen sticky taped to a piece of cardboard and inserted into a zip-lock bag.
Topic 8 - Crossbreeding and AM:
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I use Angus bulls in a cross-breeding program. Has the AM genetic condition been found in other breeds? What is the risk of an AM calf if joining to cows of another breed?
Short Answer:
If the females you are using to crossbreed with have:-
No Angus content - you can use AMC, AM__%, AMFU or AMF bulls without expecting any affected calves
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Some Angus content - you should use AMF or AMFU bulls to avoid any problems.
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Note: Be aware that some breeds have had infusions of Angus in the past.
Extended Answer:
Over the last century heritable arthrogryposis multiplex has been reported in several cattle breeds including Angus. For example, there are published reports from Canada and France of cases in Charolais with a statistical analysis indicating inheritance of a simple recessive gene.
There are however a number of quite different syndromes in which arthrogryposis (curved or hooked joints) is the common feature. In other words, arthrogryposis is a "symptom" of several different diseases, many of which are now known to be caused by the mutation of different genes.
In man and mouse where most of the research work has been done, several different gene mutations have been demonstrated. Even for defects with the same or similar phenotype (ie where affected calves have the same appearance) there can be a variety of different mutations affecting the same gene and sometimes mutations of separate gene, all nonetheless causing the same physical characteristics. Often each "family" or pedigree in which the particular disease occurs will ultimately prove to have a different mutation.
The current evidence indicates that quite different mutations often underlie syndromes with the same phenotype. Of course the more carefully we investigate and define the phenotype (visual appearance) of these syndromes, the more often we recognize subtle phenotypic differences in the affected calves that correlate to differences at the molecular level. However this takes time and lots of cases.
At the moment there is no reason to believe that all cases of heritable arthrogryposis that have been reported in the past in different breeds of cattle would have been caused by the same mutation as that responsible for the current AM problem in Angus calves. While this is possible it is unlikely. Heritable AM in other breeds could well be caused by different mutations in the same gene as the current Angus AM or even mutations in a different gene.
With regard to the Charolais cases in Canada, the published reports suggest the phenotype was not identical to the current AM problem in Angus, further supporting the likelihood of a different underlying mutation. However, even if these two syndromes are caused by separate mutations, AM affected calves could nonetheless still occur in Angus x Charolais if both mutations affect the same gene and thereby result in the production of two albeit differently defective gene products and no normal product. Normally any recessive mutant allele for a particular gene can only cause an abnormal calf if the calf inherits two copies of the mutant allele, one from either parent. In other words, the calf must be homozygous for the recessive mutation to show the abnormal phenotype. The genetic phenomenon by which an abnormal calf results when two different mutations are inherited, one from each parent, is termed compound heterozygosity.
Although there is some risk of compound heterozygosity in crossbred cattle, we believe this risk is quite low because the current prevalence of any gene mutation that might cause arthrogryposis in other breeds such as the Charolais is apparently below the level at which cases are occurring. Accordingly, the risk of AM affected calves occurring amongst the progeny of F1 Angus crossbred calves is low. Conversely, the risk of cases occurring amongst the progeny of F1 Angus crossbreds that are back-crossed to Angus bulls to produce F2 Angus crossbreds could be quite high if the Angus bulls used in this crossbreeding are not AMF.
In conclusion, based on what we know about the AM syndrome to date it appears that the risk of AM affected calves occurring in crossbred cows joined to AM carrier (AMC) bulls is very low unless the crossbred cows are also themselves descendents of Angus bulls from the affected bloodline.
That does not mean that it is sensible to join AMC bulls or bulls that have a high risk of being AMC to crossbred cattle in the future. AMC bulls should be avoided if replacement breeding females are kept from the resulting progeny. In crossbreeding, regardless of the breed or crossbreed of the parent cows, every Angus AM carrier bull (ie every AMC bull) will produce, on average, at least 50% of his progeny that are themselves carriers of the AM mutation. If some of the cows are also carriers there may also be some AM affected calves born.
Using AMC bulls in cross-breeding where heifers are retained or sold as future breeders will disseminate the AM gene in the commercial cattle population. This will create a situation where commercial breeders who unwittingly use unidentified carrier (AMC) bulls in the future over these females or their descendants could get AM affected calves.
- What
is the risk of an AM calf if joining an AMC bull to Limousin cows?
Jason Schulz, Coonalpyn
Answer:
We are not aware of any confirmed reports of heritable arthrogryposis multiplex (AM) occurring in the recent past in any other purebred cattle in Australia. We are also not aware of any reports of outbreaks of arthrogryposis in Limousins anywhere in the world that suggest a heritable condition in that breed. However, like most Continental breeds in North America, the Limousin breed in North America has recently accepted infusions of Angus genetics in animals registered in its herdbook. Nowadays it is therefore quite possible that some Limousins and particularly black Limousins (and black Simmentals for that matter) could potentially be AM carriers (AMC). The same applies to many Red Angus and composite cattle in Australia as these breeds have also apparently been using black Angus bulls that are now known to be AMC
(26/08/2009)
- What is the risk of an AM or NH calf
if joining an AMC or NHC bull to Murray Grey cows?
Answer:
While the incidence of AM and NH is likely to be low in the Murray Grey population, producers with Murray Grey cattle need to be aware that there is the possibility of the AM mutation being present in some Murray Grey animals that have been bred up from Angus.
- I have a bull with an AM_% of 11 %. His grandsire is an AM carrier. I don’t understand why he doesn’t have an AM_% of 25 %?
Answer:
A software program called GeneProb is being used which uses the DNA test results and AA pedigree database to calculate the probability of untested animals being carriers.
GeneProb looks at the status of the parents and contributes a probability to the progeny. It also looks at the status of the progeny and contributes a probability back to the parents. In this case it has resulted in the animal having a lower than expected % if you were only to consider the AM status of its ancestors. In other cases it can result in an animal having a higher AM_% than its' parents.
For this case study the dam of the bull has an AM_% of 22 %, but we would have expected that as the daughter of an AM carrier bull she had a 50 % chance of carrying the AM gene. The reason for the difference is that she has some progeny and grand-progeny that have tested AMF, and this data feeding back up the pedigree tree has reduced her probability of carrying the AM gene.
The bull’s status of AM11% is then simply half of the chance of his dam being a carrier.(26/08/2009)
Topic 10 - Validation of the AM DNA test
- Has the AM DNA test been validated?
Peter Meynink, TerrigalAnswer:
Below is a section from an article by Dr Jonathan Beever, Associate Professor of Molecular Genetics at the Department of Animal Sciences at the University of Illinois. Dr Beever developed the test.“Using breeder reports on AM affected calves as well as DNA samples obtained from these calves and many of their parents, we have been able to identify the gene and mutation that we believe is responsible for the genetic abnormality. As part of the test development, we have been able to provide the genotypes and AM status of 736 AI sires. These sires were used as an essential part of our research because a broad cross section of genetics representing the Angus breed is necessary to assess the validity of any diagnostic test that is developed.
After identifying the specific mutation, experiments were conducted to validate the relationship between the mutation and AM. Based on these experiments, we believe that the scientific basis of the test is accurate; in other words, testing for this specific mutation will lead to correct classification of any animal. In regard to the diagnostic assay that is used for determining an animal’s AM status, the test has undergone several optimizations that also lead us to believe that the test is highly reproducible and accurate. However, as with any task requiring human intervention, errors can occur. Of course, we do our best to limit any errors that occur by automating portions of the test and appropriately incorporation of testing controls. Although we cannot guarantee perfection, we estimate the assay may have an error rate of around 1 in 10,000.”
It has been felt that there hasn’t been a need for an independent validation of the test because:
17/02/2009
Contact Details:
Dr. Mary Carr
Veterinary Officer, Disease Surveillance
PIRSA Glenside
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Phone: 08 8207 7872
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Mobile: 0437 328 592
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Angus Society of Australia
86 Glen Innes Road
Armidale, NSW, 2350
Australia
Email: office@angusaustralia.com.au
Phone: +61 2 6772 3011
Fax: +61 2 6772 3095