On Sept. 5, 2008, the American Angus Association posted a notice on its Web site requesting assistance in obtaining reports of any abnormal calves believed to fit the description of what was called “Curly Calf Syndrome." On Nov. 3, Jon Beever, DVM, posted a description of the mutation and identified the status of over 700 A.I. bulls. In a mere two months, researchers obtained samples and pedigrees from affected calves and their parents, the mutation was identified, and a DNA test was developed and validated.
Arthrogryposis Multiplex (AM) is a lethal autosomal recessive defect recently reported in Angus and Angus-cross calves. In just a few months AM has undergone multiple name changes, including Curly Calf Syndrome (CCS), Bovine Hereditary Arthrogryposis Multiplex Congenita (BHAMC) and Muscle Hypoplasia, Arthrogryposis, and Kyphoscoliosis (MAK). The name Arthrogryposis Multiplex reflects the prominent phenotypic characteristics, while not resulting in confusion with a similar phenotype observed in Akabane or other similar Simbu viral disorders seen in Australia and referred to as Curly Calves.
Calves with AM are born dead or die shortly after birth. They are small for gestational age and have markedly diminished muscle mass. It appears that in AM there is a deficit in the development of the neuromuscular junction, thus causing lack of fetal movement in utero and resulting in tetramelic arthrogryposis. There are several landmark characteristics of AM including arthrogryposis, kyphoscolosis, and decreased muscling. The forelimbs are invariably in fixed flexion, with fixed flexion of the forelimb pasterns. The hindlimbs are usually in fixed extension, with fixed extension of the hindlimb pasterns, but the hindlimbs may be in fixed flexion in some cases.
In addition to kyphoscoliosis, calves with AM have torticollis, and associated abnormalities of the ribs and sternum. There may also be cleft palate, cranial doming and lateral deviation of the facial bones. The ear pinnae are often set lower than normal and closer together on the back of the skull. There is no destruction of the brain tissue. The most obvious histopathological finding is the lack of muscle organization and adipose infiltration.
The genetic cause of AM was suspected when pedigree analysis of the original cases found that all affected calves trace on one or both sides of their pedigree to GAR Precision 1680 (#11520398) — a bull born in 1990 and used heavily for his carcass genetic merit. Later investigation revealed that those AM calves that did not trace to 1680 on both sides of the pedigree did trace to his maternal grandsire, Rito 9J9 of B156 7T26 (#9682589), who has subsequently been determined to be a carrier of AM. Sons and grandsons of 9J9 and 1680 were exported to Australia. Laurie Denholm, BVSc, PhD and other Australian researchers were instrumental in providing information and samples for the process of identifying the mutation.
In accordance with the suggestion of the World Holstein Friesian Federation the genetic nomenclature used designates carrier individuals as AMC and those free of the mutation as AMF.
Beever and Brandy Marron of the University of Illinois have identified the mutation involved in AM. The mutation is a deletion that involves three genes — one of these genes is involved in the development of the neuromuscular junction. Affected calves are missing ~23,000 base pairs of DNA. These missing base pairs result in complete loss-of-function of all three genes in homozygous calves. Once the mutation for AM was identified they developed and validated a DNA based test. As part of test development the AM status of 736 AI sires was determined. The results of these tests are posted on the American Angus Association Web site. It was felt by the researchers, the AI studs, and the AAA that it would beneficial to release these results to the industry prior to the breeding season. Breeders can thus avoid using carrier bulls on untested cows with 9J9 in their pedigree.
To date only Angus and Angus-cross cattle are known to be affected by this mutation. A condition with similar appearance has been reported in Charolais cattle, but the genetic basis of this disorder has not been determined.
For genetic defects to be recognized by producers there has to be a “critical mass” of abnormalities to raise a red flag and cause concern. Many producers would think nothing about having one “weird” calf, but when the numbers increase, and our neighbors have the same issue, and maybe the vet becomes involved, we start to think genetic. The use of artificial insemination and embryo transfer has dramatically increased both the desirable traits and the less desirable and potentially lethal traits within the population of cattle worldwide.
The American Angus Association has information on AM, test results, and approved laboratories listed on their Web site. In addition, animals that are tested as carriers of the mutation are listed under their pedigree (www.angus.org/registeredangus/).
This case study was contributed by Lana Kaiser, MD, DVM, Mason, Mich.
Currently, there are 5 laboratories approved by the AAA to run the AM test—each has different sample requirements and costs.
1756 Picasso Avenue
Davis, Calif. 95618
(800) 311-8808, ext 3016
2399 N. 1000 E. Road
Mansfield, Ill. 61854
Pfizer Animal Genetics
250 Plauche Street
Harahan, La. 70123
1-877-BEEF DNA • 1-877-233-3362
4701 Innovation Drive, CB 101
Lincoln, Neb. 68521
1-877-IGENITY • 1-877-443-6489
4665 Innovation Drive, Suite 120
Lincoln, Neb. 68521