Potential genetic defect in Shorthorn cattle

[knabe]

i got a few phone calls and emails to keep quiet.

did this one ever get found?

http://calfology.com/library/article/retinal-dysplasia-and-internal-hydrocephalus-shorthorn-calf

 

[DL]

i got a few phone calls and emails to keep quiet.

did this one ever get found?

http://calfology.com/library/article/retinal-dysplasia-and-internal-hydrocephalus-shorthorn-calf

The current issue appears to be slightly different from the one in the article - it is hydrocephalus and cleft palate - if I recall less than 10 have been noted - a couple of samples have been submitted and pedigrees from other affected calves (it is lethal) are similar - but that is as far as it got - not enough samples to identify the mutation

 

[oakview]

From yesterday afternoon:  This defect does take two carrying parents.  2 or 3 months ago it was thought it only took one, behaving differently than TH and PHA.  It was thought that approximately 5% of the offspring of a carrier parent mated to a non-carrier parent would display the defect.  I am happy this is not the case.  There seems to be some relationship between the presence of the PHA gene and the appearance of DS.  Perhaps this explains why it didn't show up sooner in Improver offspring since PHA didn't appear on the scene to my knowledge in the 70's or at least Stinger and his ancestors were not commonly mated to Improver offspring at that time.  Again, call Patrick Wall with the ASA and he can fill you in far better than I.  I am repeating what I was told, hoping I didn't lose anything in the translation. 

 

[knabe]

So affected calves are hetero for Pha and ds?

 

[oakview]

The way I understand it is that the PHA gene does not have to be present, but the incidence rate of DS is higher if it is.  I also understand that if the parents have that "club calf" look, short pasterns, very straight hind legs, etc., the rate of incidence is higher.  It doesn't sound like this defect behaves exactly like TH or PHA where if you mate two carriers, you'll get 25% defective, 50% normal, but carrying the gene, and 25% normal without the gene. Perhaps this explains why there is such a variance in visual appearance of the affected calves.  The defective calves I have seen range from very deformed to almost looking like a good foot trimming would fix them right up.  I'm feeding out a couple of these calves for a friend of mine and there is quite a difference in the two.  The roan heifer is so good, maybe I'll trim her feet and advertise her on steer planet.  Just kidding.  That won't happen.  Remember, I am not a scientist and didn't even stay at a Holiday Inn last night. 

 

[aj]

The calf that I x-rayed......if I remember right......went back to Suds on the bottom side. PHA deal. I don't understand what about Improver though.....he wasn't pha was he?

 

[oakview]

Deerpark Improver is not PHAC, but Suds (through Stinger I assume) is to the best of my knowledge.  The PHA gene doesn't have to be present for DS to be expressed, just makes it a little more likely, the way I understand it.  Maybe a companion in a certain kind of cattle.  Patrick Wall is worth a phone call.

 

[knabe]

i think it's just best to wait for an official notice.

 

[DL]

OK - since I started this thread way back when - here is what I now know -( interestingly we seemed to understand the variable penetrance and the mode of inheritance pretty well before we knew the mutation and the whole story - )

DS is inherited as an autosomal recessive (like TH and PHA) - to have DS both parents must be carriers

BUT DS it is kinda complicated

AND there are some differences between DS and TH or PHA

1) Variable penetrance - we know there is variable phenotypic expression (ie some are severely affected and do not survive and some are "almost normal") - this is because the mutation alters a gene that makes a protein - sometimes that protein is not functional and sometimes it is partially functional - this leads to the variability of what we see. Penetrance is defined as the frequency with which a heritable trait is manifested by individuals carrying the principal gene or genes conditioning it. So for DS some homozygous animals are severely affected and some are not

2) Both the DS mutation and the PHA mutation are on the same gene - calves that carry the DS mutation (from one parent) and the PHA mutation (from the other parent) are susceptible to developing the DS phenotype - again it has to do with a functional protein - further these calves are likely to have more severe pathology

We were able to get x-rays, a CT scan and a full necropsy of the DS calf shown below which helped to determine that the abnormality was confined to the distal hind limb - thanks JT also thanks to everyone who submitted samples (including the stew meat sample)

 

[knabe]

Are they ever going to publish a paper on this?  One never came out for Pha.

 

[knabe]

Have snps in this gene affecting the protein been found in other phenotypes, ie stiff pasterns, slipping pasterns, spastic paresis monkey mouth other developmental ?

Any changes that don't terminate the protein but still cause problems?

 

[aj]

So DS isn't nessecarily a "Improver" thing......or is it......or maybe?

 

[oakview]

I was told it was an "Improver thing", but it was from a breed ass'n. rep., so it might not be official.

 

[Okotoks]

I was told it was an "Improver thing", but it was from a breed ass'n. rep., so it might not be official.

I have never seen the defect but given the fact it doesn't always express itself the same way it I suppose it could skip along for a few generations without showing up. We did do some linebreeding to Deerpark Improver 2nd at one point and never had any issues. I wonder if Deerpark Improver 2nd dodged the bullet with both TH and DS?

 

[oakview]

According to the ASA website, Improver 2nd is TH free.  I would not worry about any defects being passed from old Improver to Improver 2nd.

 

[DL]

I was told it was an "Improver thing", but it was from a breed ass'n. rep., so it might not be official.

I have never seen the defect but given the fact it doesn't always express itself the same way it I suppose it could skip along for a few generations without showing up. We did do some linebreeding to Deerpark Improver 2nd at one point and never had any issues. I wonder if Deerpark Improver 2nd dodged the bullet with both TH and DS?

I don't know if "skip a generation" is the right way to think about it as a DS homozygote can look almost normal but still be homozygous for the mutation so bc of the penetrance issue they may look phenotypically normal but genetically carry 2 copies of the DS mutation. So it hasn't genetically skipped a generation it has just been variable in its phenotypic expression (ie what you see)

DS goes back to Deerpark Improver (and may go beyond that but without samples we will never know) -

What kind of questions do people have about DS - if you could ask anything what would you want to know?

 

[aj]

If bull A.......who sired a defective calf......sire sons who were free of DS? And is DS a deal.......like th.......where a certain look occurs with carriers?

 

[knabe]

What kind of questions do people have about DS - if you could ask anything what would you want to know? [/color][/size]

what pathway/s is this gene in? to me, it's the DS/PHA gene.

why are genes more or less susceptible to mutation?

what rates do snps occur in each protein position and are those occurrences influenced by anything such as gene position with respect to telomere, centromere, other landmarks on the chromosome?

is the DS snp before or after the PHA snp

how far is it from the 3' end of the mRNA and the end of the protein (in relative terms so as to not give away anything)

what other organisms have mutations in this gene and what are their effects?

if they are known, are the causal snps clustered or random in location?

is a paper in review for publication describing the gene's function?

is it on the same gene as any other defects?

what % homology does this gene in shorthorns have with maine's through the rest of the gene, other breeds?

 

[sue]

DL

Is there a marker for DS ? Can I send a sample to Jon and know if I have a carrier for DS?

 

[oakview]

When I was told about the testing procedure some time ago I was told that they had to be blood samples.  All that I was told at that time has proven to be correct with the exception of taking 2 carrier parents as opposed to 1 as was thought a few months ago.  Is the blood sample still a requirement?  I was given a different address than where we used to send our TH tests at U of I.  I was also told there had to be separate samples for DS and TH/PHA/DNA testing.  It would be convenient if they could all be done at once at the same place.