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Woodmagic Wheatear #2406
 (suggested source in N.American Dexters) 

PHA
(Pulmonary Hypoplasia with Anasarca)

Maine Anjou breeders manage oldest genetic mutation

(This article is copied, in it's entirety, with permission from Midwest Ag Journal. Their web address is copied following  the article)  

 

“PHA looks to be the oldest mutation we have dealt with. It continually pushes down through generations having continual sequential breed downs,” said Universityof Illinois researcher, Dr. Jon Beever.

By Jennifer Bremer

In 2005, the Maine Anjou breed was affected by a genetic defect that eventually was traced back to a bull born in 1970.

Pulmonary Hypoplasia with Anasarca (PHA) is a lethal recessive disorder which affects Maine Anjou and Maine Anjou influenced cattle. The calves have little, poorly formed lungs, and they have lots of excess retained fluid. The calves are usually born dead and may be aborted early. “At the onset, June 2005, the AMAA had just been introduced to the potential genetic problem,” said John Boddicker, executive vice president of the AMAA. “An immediate research program was set in motion and a notification letter was sent to the entire membership in September 2005.” Indiana veterinarian Dr. Chuck Hannon had discovered some of these PHA calves while he was researching Tibial Hemimelia (TH) in the Shorthorn breed. Some Shorthorn calves thought to have had TH actually were PHA calves.


FLUID-FILLED—A close-up of the PHA calf’s head. Notice the complete loss of detail due to the fluid accumulation. (Photo provided by Jennifer Bremer.)

University of Illinois researcher Dr. Jon Beever had been working with Dr. Hannon with TH testing and then became aware of PHA.

Dr. Beever then began the search for the gene causing PHA. PHA was a bit of a challenge since it overlapped some of the same cattle which were carriers of the TH gene. “With PHA we had to rely heavily on breeder reports and samples in order to develop the test,” he said. “Now we know cattle can be carriers for both TH and PHA or perhaps other genetic mutations and that they aren’t linked to each other.”

PHA, unlike some of the other genetic defects, will cause early term abortions, which leads to open cows. Dr. Beever said this made many breeders unaware of the PHA problem, often blaming the open cows on other health issues.

With PHA, embryo loss at 90 to 180 days can be as high as 30 percent. Calves that do survive and go full term or near full term often times must be delivered via cesarean section. Calves can retain so much fluid that an 80-pound calve can weigh as much as 200 pounds. Often times difficult deliveries can lead to extreme damage to the cow and may lead to problems with future breeding or even survival, according to Beever.

Old mutation

“PHA looks to be the oldest mutation we have dealt with. It continually pushes down through generations having continual sequential breed downs,” said Dr. Beever. After much research and pedigree search, the mutation was traced to three commonly used AI sires in the American herd. Due to incomplete or inaccurate pedigrees or the inability to obtain samples from older full-blood Maine Anjou cattle, Beever said molecular markers surrounding the gene suggested a bull born in 1970 to be a common source for the mutation.

While the Maine Anjou breed is considered the source of PHA in the U.S., with the allowance of registering percentage cattle in some breed registries, PHA has been found in other breeds as well.

The genetics

PHA, like other recessive defects, can only show up when two carriers are mated to each other. Affected calves are rarely tested for the defect and some are aborted too early to be tested; however, those calves would be considered homozygous for the mutation. A PHA carrier (PHAC) would be heterozygous for the mutation. Using the genetic information known on two animals, a breeder can determine the chances of having an affected calf, according to Dr. Beever.

He explained: “If the normal gene is “P” and the defective gene is “p,” mating a carrier bull with the genotype Pp for the PHA gene to a carrier cow also with the genotype Pp for the PHA gene will result in three calves that look normal at birth, but two of the three will be PHA carriers (Pp). The fourth calf will be born with PHA (pp). Thus, mating two carriers gives a breeder a 25 percent chance of having a PHA calf every time this mating is repeated.

“Mating a carrier bull or cow to a non-carrier cow or bull will result in 50 percent of the calves being PHA carriers (Pp). A non-carrier or PHA-free (PHAF) animal would have the genotype PP.”

Abnormality policy

Beginning Feb. 1, 2006, the AMAA required AI sires, donor dams and cloned animals to be tested for genetic defects. Their initial focus was on PHA and TH, with the thought that other defects may be addressed as needed.

The AMAA publishes a list of animals which have been tested and their carrier status. While PHA seems to be somewhat under control at the breeder level because of testing which has been available, Boddicker said it is important for breeders to continue to report cattle which are affected by the gene.

“Breeders can utilize the commercial test and most importantly use common sense in their breeding schemes. Over time the PHA issue will take care of itself,” said Boddicker. “The key to a quicker resolve in these genetic issues is open communication and a steady stream of documented information.” Genetic problems should be reported to the AMAA or a veterinarian for further research. Jennifer Bremer can be reached by phone at 515-833-2120 or by e-mail at jbremermaj@hotmail.com.

GENETIC DEFECT—The Maine Anjou breed and Maine Anjou influenced cattle have been affected by a recessive genetic disorder over the past few years. (Journal photo by Jennifer Bremer.)

PHA5 PHA-AFFECTED—This Maine Anjou calf with PHA is full of fluid and weighed about 200 pounds at birth. Delivered via c-section. (Photo provided by Jennifer Bremer.)

PHA11


Proper testing procedures get accurate results

By Jennifer Bremer

With many different genetic defects coming onto the forefront in several different breeds, it is important to know how to properly collect samples for testing animals to determine their status. Dr. Jon Beever at the University of Illinois and AgriGenomics lab performs tests for Arthrogryposis Multiplex (AM), Tibial Hemimelia (TH), Pulmonary Hypoplasia with Anasarca (PHA) and Idiopathic Epilepsy (IE), as well as other non-defect tests.

Dr. Beever has developed the tests for these defects, but other labs are performing the tests in some cases.

“With TH and PHA, it was more of a niche market and we estimated the number of tests per year to be what we could handle,” he said. “With the IE test, the American Hereford Association has a contract lab. The AM test will likely be performed by several different labs.”

Dr. Beever said each lab will have its own set of protocols for sample collection procedures. Currently, three labs are online to do the AM test with more expected.

The procedures used at Dr. Beever’s lab are to use either blood or semen samples. When taking blood samples, new needles and syringes should be used for each collection to prevent contamination. The sensitivity of the test can detect very small quantities of contamination potentially producing invalid test results.

Blood samples

• Collect at least 2 cc of whole blood in an EDTA purple top tube. An anticoagulant is used in the purple top tubes to keep the blood from clotting.

• After collecting the blood, the tube must be mixed thoroughly by inverting 5-10 times. Severely clotted blood samples received will not be processed and must be resubmitted.

• Blood tubes must be labeled with the animal's permanent ID and/or registration number, making sure to label the tubes correctly.

• Samples should arrive at the laboratory within 48 hours of collection for best results.

• When temperatures exceed 90 degrees for extended periods, samples should be packed with a cold pack but not frozen.

• When temperatures are below 35 degrees, samples should be in an insulated container to prevent freezing.

Semen samples

If sending a semen sample for testing, producers should:

• Send at least one straw of thawed semen.

• Semen straws should be protected from breakage during shipment by placing them in a semen cane or goblet and packaged in a padded envelope or small box.

• It is important to mail the straw in a protected envelope to prevent crushing during handling.

Other instructions

It is important to include all the pertinent information with the samples. Individual breeds have submission forms available on their websites. Samples sent to AgriGenomics will not be processed without payment.

Written results are provided on all samples tested. Each breed association is handling the results differently. Some require proof of test results prior to registration, while others allow carriers to be registered, but the animal’s genetic status to be known prior to the entry of an animal in an association sponsored sale.

For more information on testing, visit individual breed association websites or AgriGenomics website at www.agrigenomicsinc.com.

Jennifer Bremer can be reached by phone at 515-833-2120 or by e-mail at jbremermaj@hotmail.com.

12/29/08
None\7-C

Date: 12/22/08

Jennifer Bremer is Field Editor for Midwest Ag Journal
 
 Use this link for this Jennifer Bremer informative article
"Maine Anjou breeders manage oldest genetic mutation"
 
 
ADCA PHA FACT SHEET
(Pulmonary Hypoplasia with Anasarca)

 

This fact sheet addresses the most commonly asked questions about a genetic defect that has recently been confirmed by DNA-testing in several breeds of cattle, including the Dexter breed.

 

The questions and answers presented herein are based on the conclusion that Pulmonary Hypoplasia with Anasarca (PHA) is the result of a mutation in a specific gene.  Dr. Jon Beever, of AgriGenomics, Inc., has developed a genetic test that identifies the presence of this mutation in this specific gene.    

 

1.  What is Pulmonary Hypoplasia with Anasarca (PHA)?

 

“Pulmonary” refers to the lungs and “Hypoplasia” means incomplete formation, thus “Pulmonary Hypoplasia” means incomplete formation of the lungs.  “Anasarca” means a general accumulation of serum fluids in various tissues and body cavities; thus anasarca results in swelling and a swollen appearance.   Pulmonary Hypoplasia with Anasarca is the result of a genetic defect.

 

In order to be PHA-affected, a calf must inherit a PHA-allele from both its sire and dam.  Since the PHA-allele is recessive, the lethal form of this condition is only expressed when the calf is homozygous for the PHA-allele.   PHA-affected calves are either aborted or stillborn.  Because of the anasarca, associated with this condition, the PHA-affected calf may also swell tremendously with fluid, making delivery difficult and potentially endangering the life of the cow.

 

2.  What is a gene?  What is the difference between a gene and an allele?

 

A gene is a sequence of DNA which provides the basic instructions or “code” for a certain trait or function.  Genes are the hereditary information that get passed from one generation to the next, and they can have alternate versions.  An alternate version of a single gene is called an allele.  Genes occur in pairs.  For each pair of alleles, one is inherited from the sire and one is inherited from the dam.  Alleles can be dominant, co-dominant, or recessive.

 

The allele for PHA is recessive.  The PHA-allele does not have the normal sequence and number of base pairs needed to code properly for its functions.  It is a mutation of the normal allele.  Since alleles occur in pairs, an animal that has one PHA-allele and one normal allele will be not be affected by PHA, but it will be a carrier of PHA.  Since the normal allele is dominant in this pair, it will code properly for its functions and normal development of the lungs will occur. 

  

3.  What is a mutation?

 

A mutation is a permanent change in the DNA sequence that makes up a gene.  Mutations can range in size from a single DNA building block (a base pair) to a large segment of a chromosome.

 

The PHA-associated mutation in Dexter cattle occurs on the same gene as the PHA-associated mutation in Maine-Anjou and Shorthorns, but it is a different change in the DNA sequence, so it is considered to be a different mutation.  It results in the same outcome because the same gene is damaged and cannot perform its intended function.

 

4.  Is PHA due to a recent mutation?

 

We don’t believe so.  The Journal of Anatomy and Physiology in Great Britain, published in 1906, page 293, references the following:  “Lesbre and Forgeot describe another achondroplasic calf which was born dead in an extraordinarily anasarcous condition.  Dissection showed that both kidneys were absent.”  Since Lesbre and Forgeot were dealing with “bull-dog” calves that were found only amongst the pure Dexter-Kerry breed, they may have confused a PHA-affected fetus with a Chondrodysplasia-affected fetus, or it may have been a fetus affected by both conditions. 

 

The first tested and confirmed PHA-carrier in the Dexter breed is Trillium Chabotte, ADCA #3168.  His semen was tested in Australia and the test result was very recently reported through Dexter Cattle Australia, Inc.  This bull was born in 1985, in Canada.  He was collected for artificial insemination and his semen was used in Canada and exported to Australia.  Though he has only 9 registered progeny in the ADCA; according to the ADCA Online Pedigree, as of January 12, 2009, he has more than 3,400 registered descendents in the ADCA registry.

 

The ability to genetically test for the PHA mutation is very recent.  The PHA mutation itself is not considered to be a recent occurrence.   

 

5.  What is a PHA-affected calf?

 

A PHA-affected calf is a calf born dead with underdeveloped lungs (Pulmonary Hypoplasia) and swelling caused by excessive fluid retention (Anasarca).  When genetically tested, this animal has two PHA-alleles for this specific gene, it is homozygous for PHA. 

 

 6.  What is a PHA-carrier?

 

A PHA-carrier is an animal that has one PHA-allele and one normal allele in its gene pair, it is heterozygous for PHA.  A PHA-carrier appears normal, there is nothing in its appearance (its phenotype) that indicates the animal is a carrier of the PHA mutation.

 

7.  Can an animal be a non-carrier of Chondrodysplasia and still be a PHA-carrier?

 

Yes, the two genetic conditions are not related to each other.  Two different tests are used to determine the status of these two unrelated genetic conditions.  An animal can be a non-carrier of either, both, or neither. 

 

8.  Can a “bulldog” calf also be a PHA-affected calf?

 

Yes, a severely affected Chondrodyplasia ( “bulldog”) calf, can also be a PHA-affected calf, if it is homozygous for the Chondrodysplasia allele and is also homozygous for the PHA allele. 

 

With a dead, deformed Dexter fetus that has not developed sufficiently, it may be difficult for a breeder to discern which condition lead to its death.   There are also other factors that may result in abortion or stillbirth of a calf, so those factors should not be ruled out without a DNA-test of the fetal tissues to confirm its PHA and Chondro status.

 

9.  If a bull sires a PHA-affected calf, what does that mean?

 

If a bull sires a PHA-affected calf, it means that the bull is a PHA-carrier and the dam is also a PHA-carrier.

 

10.  If a cow has a PHA-affected calf, what does that mean?

 

If a cow has a PHA-affected calf, it means that the cow is a PHA-carrier and the bull she was bred to is also a PHA-carrier.

 

11.  If I’ve never had a PHA-affected calf, does that mean that my cows are non-carriers of PHA?

 

No, a cow’s status as a non-carrier of PHA can only be determined by genetically testing the cow.

 

12.  How do I test to determine the PHA-status of an animal? 

 

The ADCA is actively promoting PHA testing for all Dexter AI bulls to build the initial knowledge base needed to determine the extent or potential extent of the number of PHA-carriers that may currently exist.  This is a recently developed test, and at the present time, only semen or blood samples can be tested in the United States.  Efforts are underway to develop and make available a test procedure that uses tail hair samples.

 

Note:  Semen samples for more than 30 Dexter AI bulls have already been submitted for testing and we are awaiting these test reports.  A list of these results will be posted on the ADCA web site and published in the ADCA Bulletin.  
 

13.  What can happen when a PHA-carrier is bred to another PHA-carrier?

 

Every time you breed a PHA-carrier cow to a PHA-carrier bull, there is a 25% probability of having a dead PHA-affected calf.  There is also a 50% probability of having a normal-looking calf that carries the PHA-allele, and a 25% probability of having a normal-looking calf that is a non-carrier of PHA.

 

14.  What can happen when a PHA-carrier is bred to a non-carrier of PHA?

 

Every time you breed a PHA-carrier to a non-carrier of PHA, there is a 50% probability of producing a PHA-carrier and a 50% probability of producing a non-carrier of PHA.  You will never have a PHA-affected calf if you breed a PHA-carrier to a non-carrier of PHA.

 

15.  What are the recommended “best practices” to breed the cows in my herd that are confirmed as PHA-carriers and conserve their desirable genetic traits?

 

  • Breed only to a bull that has been genetically tested and confirmed as a non-carrier of PHA.
  • Test any calves that you produce and intend to retain or sell as registered breeding stock to determine their PHA-status.  Make careful selections based on that knowledge.  Inform prospective buyers of the PHA-status on any registered breeding stock that you offer for sale.
  • Retain the offspring that are non-carriers of PHA and that have the desired traits you wish to propagate within your herd.  Gradually replace your PHA-carriers as they become old and unproductive with these carefully selected non-carriers of PHA.

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P.O.Box 135
Antelope, OR 97001
 

 

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