PHA hot off the presses!

Well we all know about PHA, recessive genetic disease in cattle, described recently in Maine -Anjou and tracing back to 3 bulls at about the same time (implying that a common ancestor was involved in passing the defective gene to all 3 bulls at the same time).  These bulls are Draft Pick, Stinger and Payback. Dr Beever and his trusty side kick Barrel Racer have identified the gene and the defect and so now we can test for PHA (Hallelujah  ;D)

We have trundled back thru Draft Picks pedigree and found that his sire (Nortex General) and his maternal grand sire (AA Black Gold 500) are PHA free - making his dam a suspect, and low and behold her sire Paramount is a PHA carrier. To date he is the only old Maine bull that is identified as a carrier. ALso interesting is that we cannot connect Draft Picks pedigree with Stingers - although the defect is the same. Payback has an incomplete pedigree.

Big deal, you say, nothing new there, but wait......

Recently a group in Australia described PHA in Dexter cattle ( in Australia are not considered a "hobby" breed but a viable beef producing breed)  - some of whom were of Canadian origin (some of us wondered if we were raising big Dexters or they were raising mini Maines!) BUT guess what ------ (drum roll) the genetic defect in PHA seen in Maines is different from the genetic defect seen in PHA in Dexters (same gene, same protein involved but different defect) ----Now isn't that just so cool and interesting - who said the double helix wasn't fun! Not Watson  (clapping)

So Maine breeders are raising Maines
And Dexter breeders are raising Dexters
and both breeds have PHA
and the genetic defect is different

DL

ps I have a copy of the Dexter paper in the AUstralian Vet J if anyone wants it... (cow) (cow) (cow) (cow)

Dl, I was holding my breath afraid you were going to tell me I've raising big Dexters all this time! Really fascinating and yes, I'd like a copy of the article.
For those that aren't familiar with PHA or even TH can you give us a quick & dirty course?
As a Maine breeder it's something I've been struggling with ever since I found out about the defect. Now, knowing have some cattle with it, I've really had to educate myself. I thank both you, Dr Beever & Barrel Racer for the time you've put into it. Also Don Coover at SEK for putting out some of the first lists.
Having had 2 calves that were born with TH, it's a terrible thing. Luckily I haven't seen a PHA calf yet.
To me these aren't words we should ignore or bury our heads in the sand over.
THANKS,
Red (clapping) (cow)

How is it different DL? From what I understand, the same genes are involved, same protein. So it the physical defect different? How can they be compared? Is it like the Outcast TH mutation? Different but the same?
Help me DL, my purple tube top is coming apart!!! (OH MY!!)

DL - That is very interesting and confusiing at the same time. Any theories on the how's and why's this very same gene is defective and what are the theorist thinking when it's involving two different breeds and two different kinds of defects.
What is the defect in Dexter cattle and how is it different then the PHA in Maine cattle?  Is the pathogenesis of the two breeds different also?  Is there a common ancestor in both Maine's and Dexter's?

I don't know if that made sense?

I think we need to get genes out from Canada to explain it to us!
HEY GENES- SOS!!!!!

Red ))

Hehe...or to wake up from her nap 

Anyway I would need to look at the article and stuff.  Anyway, I would guess it is similar to the Outcast thing - the same but different.  So the same gene and resulting protein, but a different actual mutation.  There are different types of mutation...some are a change of a single nucleotide that change the "word" written out..  Others are insertiions or deletions of pieces of DNA.  And sometimes a chunk of DNA gets cut out of its rightful spot and put in somewhere else.  The thing is, if it hits the right part of the genome, any of these can cause significant changes.  In the case of PHA, it has apparently hit a very important gene.  Anyway, what DL is so excited about here, is that the fact that these are different mutations in the two breeds shows that these had a different origin.  So the Maine breeders weren't infusing Dexter blood.

Sorry if that doesn't make sense to you guys...I'm pretty sleepy here, but I can try again later if you need clarification.

So basicly what you are saying is that the Maines didn't get PHA from a stray Dexter bull wandering around loose using a step ladder & breeding unsuspecting Maine-Anjous? That the Maines have their own defect within their gene pool? That many have thought that somewhere the two breeds crossed over but by the genes being different they didn't?Golly, maybe I need that nap too! ))

Looking forward to you reading the article Gina, it's still being muddle around in the brain of mine. Now is there anyother breeds of cattle that have PHA? Besides the Shorthorns from Stinger bloodlines?

Red

The bottom line is that the Maines didn't get PHA from the Dexters and vice versa (or you haven't been raising Dexters if you have Maines!)

The article describes the defect but not the genetics. In fact the genetic differences are so hot they haven't been published yet! Talk about insider info!

Scientists do not like to divulge too much info until the data has been published in a peer reviewed publication - in other words if things (specifics) are in the lay press a scientific journal may pull it or refuse to publish it (this happened with a hairy heel wart vaccine article,  in case anyone cares! The author talked to a free lance writer and she (the writier) basically put all the results in the Hoof Trimmers Monthly (or some such name) and it was pulled from the scientific journal - listed in the table of contents but gone....

So this is what I can tell you - there are all kinds of things that can result in a genetic defect - in TH we have a deletion of a part of a gene (we call it the Improver deletion) - major cause of TH, but we also have a bigger deletion in the same gene in the same regiou (much rarer and we call it the Outcast deletion).

There are many ways a gene can be defective - a deletion, insertion, base pair switches, inversions etc - what I can tell you is that the PHA defects in MA and Dexters involves the same gene, the same region of the gene and the same protein (I don't know the name of the protein - if they told me I think they would have to insert a defective gene into my 23 rd chromosome! unlike the mafia where they would have to off me!  ;D - don't know what happens with the Shorthorn mafia - maybe shortdawg knows!)  - but they are 2 different kinds of defects!

Ain't that wild!

I have been working on a TH/PHA tutorial so we are all up to date - if the weather cooperates it shouldn't bee too long!

Heat wave here - above zero! DL (cow)

All I can add is.............YESTERDAY I RECEIVED NOTIFICATION THAT MY ICEPICK HEIFER TESTED BOTH PHA & TH FREE!!!!
Anybody want to buy a sure 'nuff gooood Show Heifer? 

DL - Why is Draftpick not listed as a PHA Carrier?

Dan

Dan - Congrats! Excellent news for you! I honestly don't know why ol' DP isn't listed - you mean on the AMAA web site? I'll check it out....DL

AAOK said:

All I can add is.............YESTERDAY I RECEIVED NOTIFICATION THAT MY ICEPICK HEIFER TESTED BOTH PHA & TH FREE!!!!
Anybody want to buy a sure 'nuff gooood Show Heifer? 

DL - Why is Draftpick not listed as a PHA Carrier?

Dan

Click to expand...

Wow Dan that is great news! I know I went into major depression when I found out the my Gold Club heifer tested positive for PHA. She was going to be a donor cow but nixed that idea fast.
Good luck with her!!
Red (cow) (clapping)

This may be a really stupid question, but how are you getting PHA test results back?  I had a donor I sent in and marked for both TH and PHA testing, I got her TH results back on Nov.22nd but have not ever seen anything on the PHA.  Thanks

Jill - email Dr B and ask for results - give him the info from the TH form.

AAOK - We didn't have to test Draft Pick to know he is a carrier but apparently he isn't listed because there were no official results as of yet! Life is certainly strange, eh! DL (cow)

Thanks DL for the update!!  Glad your on this board. ;D (clapping)  Now let's hope Dr. Beavers and Barrel Racer join us!  I miss there posts from the "other" board.  If there checking in...we really appreciate all your hard work your doing.  Thanks a heap (cow)

OK I have a smiley disease....I love these

I agree justme! The work and dedication that Dr.B and Barrel racer is greatly appreciated by me!! Makes a lot of breeding decisions so much easier! So if their reading, THANKS AGAIN!!  (welcome) (I love these things too!!

i'll try a little stab at how it could be different.  if a gene is made up as below as a cDNA, and not genomic sequence without the introns spliced, and i didn't check for stops other than TGA, one defect could be to change the C in the first TCA to a G, and the other defect would be to change the C to a G in the second TCA.  both changes would prematurely terminate the protein.  But since a product is still made in both cases, there could be a different result, albeit slight, particularly if the calf is born dead.  it would be interesting to know if there is any background with a premature stop towards the end of the protein which doesn't kill the calf.  Since i don't know what this gene does when not defective, it would be interesting to see how many other genes this gene interracts with.  I would love to be a new grad student in todays world.  now that the grunt work of figuring out how to sequence is done, all the kids coming up today won't have to worry about wanting a job like DNA sequencing gel pouring supervisor.  That era lasted about 3-4 years.  sorry for too much detail.  i'll probably hear a swoosh.

GAA TCC GAT TCA ACT GTA TCA GAA GAT
                            X                      X
GAA TCC GAT TGA ACT GTA TGA GAA GAT

Telos said:

DL - That is very interesting and confusiing at the same time. Any theories on the how's and why's this very same gene is defective and what are the theorist thinking when it's involving two different breeds and two different kinds of defects.
What is the defect in Dexter cattle and how is it different then the PHA in Maine cattle?  Is the pathogenesis of the two breeds different also?  Is there a common ancestor in both Maine's and Dexter's?

I don't know if that made sense?

Click to expand...

I got the invite to join the board from our pal DL, so figured I'd stop by  ;D

So just a bit of information about the PHA mutations.  I cannot mention the gene name and actual mutations due to patent and licensing issues.  They are in the same gene and the same area of that gene.  They are two different mutations that basically have the same end result, making that portion of the protein nonfunctional.  Scientifically this is interesting because the gene that is mutated is one that I would not have picked (and didn't pick) to be a candidate for this disease.  The described function does make some sense, but there are ton of other genes that would make more sense.  So, the fact that we have two different mutations in the same gene, knocking out that portion of the protein's function, with the exact same phenotype is pretty good evidence that they are the causative mutations.  I still have some work to do with the Dexter mutation, but I think that I have it characterized.  

So the fact that there are two mutations, is very similar to TH.  The difference in that I do not believe that we will ever see a TH affected calf homozygous for the Outcast mutation.  I think it is an embryonic lethal.  I think that I have the actual sequence deletion breakpoints for it (we'll know more this week probably).  The problem is that the Outcast mutation wipes out more than one gene, as it is a much larger deletion (37,000 vs. 500,000 bp of DNA).  The patent for TH is filed and waiting in line.  I'm guessing once it is granted we will try and publish the journal article.  I believe this will be one of first instances has mapped the actual deletion breakpoints for one this large, so I'm pretty excited about that.  

Jill-you will not see any written report of your PHA results yet.  We cannot send them out until the test is "official".  I would call AgriGenomics and see if they are done, if so they should be able to tell you verbal results.  Along that note, the reason that there are not more carrier animals listed on say the AMAA site is that until the test is official we cannot release any results to them.  If you're concerned about a bull, I'd just call the owner and ask if they've had him tested.

Thanks so much for the compliments for the research we have done!  TH and PHA have by far been the most interesting projects (as well as frustrating at times) I've had the opportunity to work on, but it's great to see an end result and actually seeing people able to use something you have done.  We should all also thank all of those who sent us samples when we requested them, kept an eye out for affected calves, sent samples of those, etc...  I can't do anything without any samples, so anything we can do is because of them.  

Well not to jabber on...... If anyone has any questions, I'll try and answer them as best I can.

Barrel Racer & Dr B, I think I can speak for all of us (welcome) (clapping) (welcome) (clapping) (welcome) (clapping)
Now, how's that for going crazy with the smilies?
Red

Knabe, (welcome)
Yep you were right SWOOSH!
But I do agree that that it's an exciting time in the fields all around. I just heard that they can take a woman who has breast cancer & by looking at her markers determine if she'll develop it again. Fascinating information. Especially for someone like me, an 11 year survivor.
Thanks for joining us!
Red

just me - think you should be seeing them soon - and thanks for the thanks (I like all the little critters too but where's the beef!) DL (cow) (cow) (cow)