Okotoks said:
If you think Shorthorn breeders are special in that regard you need to get out more
: : ??? ???
: : ??? ??? My information is accurate and my desire to have individuals submit samples is sincere.
Perhaps a little history of TH will shed some light on the current issue and put the numbers in perspective ...the pattern of defect and mutation identification, human and breeder responses to this potential defect is no different than that we have seen in the past with TH, PHA, AM, NH, OS, MA, EI, DM, CA etc etc
In 2000 Dave Steffens and colleagues reported 6 cases of TH (3 from the US and 3 from Canada) and concluded that the abnormality was genetic and inherited in an autosomal recessive fashion - abstract below
Vet Pathol 37:508–511 (2000)
Tibial Hemimelia, Meningocele, and Abdominal Hernia in Shorthorn Cattle
J.-M. LAPOINTE, S. LACHANCE, AND D. J. STEFFEN
Abstract. Six genetically related Shorthorn calves were affected with the tibial hemimelia syndrome. The
lesions included bilaterally malformed or absent tibia and abdominal hernia in all animals, a long shaggy
haircoat, retained testicles in males, and meningocele in three animals. The malformations were similar to those described previously in Galloway calves. 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.
Tibial Hemimelia, Meningocele, and Abdominal Hernia in Shorthorn Cattle
J.-M. LAPOINTE, S. LACHANCE, AND D. J. STEFFEN
Abstract. Six genetically related Shorthorn calves were affected with the tibial hemimelia syndrome. The
lesions included bilaterally malformed or absent tibia and abdominal hernia in all animals, a long shaggy
haircoat, retained testicles in males, and meningocele in three animals. The malformations were similar to those described previously in Galloway calves. 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.
Sometime later, when the frequency of abnormal calves reached a level of concern, and midwest breeders and Dr Chuck Hannon started submitting samples, Dr Beever and crew identified the TH mutation(s) - this was done without benefit of the 50K SNP chip, and thus required informative pedigrees and many more samples than are needed today. Information provided on showsteers was important in educating and alerting breeders and encouraging the submission of samples. The free flow of information was encouraged.
The mutation was traced to the Irish bull Deerpark Improver (ASA # 3,684,142; born 1972), one of a few direct imports to North America. Improver was used extensively in the U.S. in the 1970s, as there are 635 direct progeny registered with the American Shorthorn Association. The defective gene has been shown to be aristaless-like homeobox 4 (ALX4), a major regulator of hind limb formation. The Improver deletion removes approximately one-third of the ALX4 gene, including the upstream regulatory sequence and involves approximately 46,000 base pairs. After identification of the Improver deletion, it was noted that although the parentage of some TH calves was DNA-verified, some parents did not test positive for the Improver deletion. Additional studies revealed that the bull TKA Outcast (ASA # 4,046,304; born 2001) possessed a larger deletion of 450,000 base pairs that overlapped the Improver deletion, and removed four genes, including ALX4. The Outcast deletion is rare and affected calves sired by Outcast were ‘‘compound heterozygotes’’ (heterozygous with the Improver mutation on one chromosome and the Outcast mutation on the other).
I have no idea how many offspring of Improver offspring are listed in the ASA herd book, but if we take 6 of 635 direct offspring this is two orders of magnitude LESS than the example provided by jamiediamond - so with 6 cases of TH we began to identify the bloodlines and mutation(s) responsible for a lethal genetic defect in Shorthorn cattle.
So TH started with the reporting of 6 affected calves, today we have 7 calves reported with a hind limb abnormality
To add a little more perspective
The popularity of the TH phenotype has led to extensive use of carrier bulls in the club calf and show cattle arena. A substantial number of cattle registered with the Shorthorn, Maine Anjou, Chianina breed Associations, as well as crossbred or composite cattle, are known to carry the defective gene. In 2004, more than half of the top 10 sires for a number of Shorthorn registrations were putative carriers. In 2005, 21 of 24 black composite AI sires offered by a single vendor were verified as carriers.
In a 2007 sire directory of popular ‘‘club calf sires’’, one-third of bulls were TH carriers, including clones and sons of a popular TH carrier bull. Of the 10 most popular Shorthorn AI sires for 2006 calves, three were carriers for both TH and PHA and one was a carrier of TH (Shorthorn Country, April 2007).
So let me reiterate what we know so far about this potential genetic defect in Shorthorn cattle
Seven cases of abnormalities of the distal leg/foot and dew claws of the hind limbs in Shorthorn calves have been reported
Hind limbs only affected, below the hock
These cases are not "classic" mule foot and the gene responsible for mule foot (LRP4) is not involved
The phenotype is variable, so one leg could be obviously affected and the other more subtly affected
Typically the calf has inappropriately placed dew claws and may have some other slight curvature or deformity at the base of the leg that makes it somewhat difficult for them to mobilize.
Most calves are born alive; severely affected calves are put down because they cannot walk; less severe can grow into it
If the calf survives it appears to "improve" as it ages (variable phenotype somewhat like like FCS)
Cases are from various geographic regions (again suggesting the abnormality has a genetic component)
All cases have similar ancestors on one side of the pedigree, a popular AI sire or his sons
All 7 cases have been genotyped; 6 of 7 share a segment of 2.7 Mb for which they are homozygous, again suggesting that it may be genetic
Discussion of this potential genetic defect in Shorthorn cattle has led to increased breeder awareness and hopefully submission of samples from potentially affected calves in the pasture or the freezer. If you have a calf with abnormal hind limbs below the hock do the right thing - submit samples
