TH and cattle

[MedGen]

This is a bit of an odd one. About 4 years ago there was a sudden spike in the prevalance of Tibial Hemimelia, a deblitating genetic condition in Shorthorn cattle in the states (USA). It was calculated to have arisen from a single sire (bull) which then spread the recessive allele to its progeny. After a while, as I said above, the prevalence spiked, most likely due to distantly related progeny encountering their cousins/grandchildren and getting the TH phenotype expressed.

 

Anyway the ASA (American Shorthorn Association) implemented a stringent protocol for dealing with this and included a list of known carriers in its monthly magazine. Since then there has been little news of it. That's the history lesson over.

 

Recently a bull was imported from Canada to Britain and was used to cross with a dam (a breeding hefer). Very strangely TH started to appear among the progeny, infact values were recorded at around 80% of progeny being affected by TH. That sounds closer to a dominant trait as a result of two carriers mating. The condition however has been confirmed as recessive.

The bull and the hefers had samples taken that were sent away for analysis back in America where the bull was confirmed as a carrier, but a large proportion of the dams were not. I don't have the exact figures here in front of me so I can't confirm this quite yet, I've got this information directly from the cattle breeder.

 

On a side note the carriers sometimes present mild symptoms, almost like sickle cell trait in carriers.

 

My initial thougts were that this could be epistatic, but there has been nothing to confirm this conjecture. In fact there has been very little research into the matter. I was wondering if anyone had either a) heard anything about TH in cattle (note there is a lot of research on this in humans), or b) had any idea how the hell a recessive condition can present with an observed phentotypic ration of 4:1?! My only other guess is that an alternative allele is present in the population that either a) effects the recessive nature of the mutant allele (something I've never heard of except in cases of epistasis and co-dominance which clearly don't apply here), or that b) a new variant that was not assayed for has the same phenotypic effect so that when brought together with the original mutant allele it presents with the disease phenotype.

 

I'm at a bit of a crossroads with this one, any ideas?

[asaroj27]

Hello sir/madam

Pedigree analysis demonstrated a mechanism by which a recessive allele in a homozygous state could be responsible for the disorder. The condition in these calves was considered the result of a recurrence of a genetic mutation affecting a putative hemimelia locus.

[MedGen]

Hello sir/madam

Pedigree analysis demonstrated a mechanism by which a recessive allele in a homozygous state could be responsible for the disorder. The condition in these calves was considered the result of a recurrence of a genetic mutation affecting a putative hemimelia locus.

 

Can you expand on that a little. I would also like to add that I am not referring to the American cases here, but the British ones. I have a copy of a pedigree analysis carried out on six American calves from LaPointe et al, 2000. The observed:expected ratio is way out, we're looking at incidences of 60%-80%, far too high for a single factor autosomal recessive trait.

 

I would also like to point out that the TH locus has not been physically mapped, the only breakthrough I am aware of is the development of a marker for detection, hence the derived pedigree analysis. There is no sequence data either, very strange considering how much of the Bos taurus genome has been sequenced and uploaded to NCBI's various genebanks.

[Psycho]

6 really isn't a large enough number to give the correct ratio, the reality of genetics is that that is what the probabilities say the calves should be, their actual phenotypes could be whatever they want within the constraints of the parents genotypes.

 

The other possible explanation is that the gene is epistatic too something else and this has yet to be realised.

 

I would have to say though you need a larger sample too start making any assessments.

[MedGen]

I think I haven't explained this properly.

 

First the confirmed, documented cases of TH in America was over a period of years, the article I mentioned was merely an example of this and a pedigree analysis of six affected calves.

 

I am trying to work out what is going on with the British calves, so far I only have a rough estimate of the afflicted calves of 60-80%. This percentage represents a number of dams, and thus a number of calves. My point is that TH is an autosomal recessive trait, that has already been worked out. What I am trying to find out is why the hell is it not following it's expected ratio's in these British calves?

 

My first assumption was epistasis, but the TH mutant allele is behaving in a dominant manner, which flys in the face of all previous tests and pedigree analysis that characterised it as a recessive allele. My next conclusion was that there is a loci in these British calves that affects the penetrance of the disorder so that it comes out with these observed ratio. I still haven't got any more figures at the moment, still waiting to hear back from the breeder.

[asaroj27]

hello sir

can you explain me the experiment of yours or tell me the result of your experiment.so that i can give you some idea(may be).

thank you

[MedGen]

This is not an experiment, it is an observation that I was told about. I did a little literature researching and turned up the LaPointe et al, 2000 paper as well as some press releases from the ASA. That is all background information.

 

Essentially I was asking if anyone had encountered and inheritance pattern like this before? As I have said already, I previously suspected the mutant allele is epistatic to another unknown loci. Is there anyway of determining whether or not an allele is hypostatic or epistatic just from pedigree analysis? Or does it require further investigations?

[Psycho]

Is there anyway of determining whether or not an allele is hypostatic or epistatic just from pedigree analysis? Or does it require further investigations?

Not conclusively you would need to obtain which allele is at the known loci and compare that with similarities between other alleles in the genotype of the other cattle as well as the individuals.

 

What size sample is this and how common is the recessive allele in the population?

[MedGen]

Not conclusively you would need to obtain which allele is at the known loci and compare that with similarities between other alleles in the genotype of the other cattle as well as the individuals.

 

What size sample is this and how common is the recessive allele in the population?

 

No idea, this is just some preliminary info I got from a cattle breeder, I don't even know what breed they are. I'm still waiting on numbers and other info. They sire and the dams may have only been genotyped for the mutant and wildtype allele though, which of course would not give any new information. I'll try chasing up the breeder and see what he says about it.