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In the fall of 2020, when Chad Dechow received a call from New York vets describing a strange condition affecting Holstein calves on two farms under their care, he was unfamiliar with the condition that became known as calf recumbency.
The animals were weak and could not stand at or shortly after birth, and most did not survive beyond six weeks of age. Veterinarians have found no neurological, infectious, or metabolic abnormalities in the very young animals. It was a mystery.
“They couldn’t figure it out, they had calves necropsied that died and they couldn’t find anything wrong,” said Dechow, an associate professor of dairy genetics at Penn State. “They contacted me because they had read an article in a popular print magazine I had written about another recessive genetic condition.”
Veterinarians sent tissue samples from two of the calf autopsies to Dechow’s lab at the College of Agricultural Sciences and an investigation began. Soon after, Dechow learned that a herd of Holsteins in Florida that use IVF for their genetic elite, which means high-yielding animals, had been experiencing a similar problem. A remarkable mating had resulted in several calves that could not stand, and herd managers sent them samples of Dechow tissue.
“Then I found a herd in Pennsylvania that also uses IVF that had a similar problem in some of their calves,” Dechow said. “So, between the two herds in New York, the herd in Florida and the herd in Pennsylvania, we were able to assemble a population large enough to start tracking the mutation. We conducted genome-wide matching using thousands of DNA markers and pedigree analysis to determine whether a genetic origin for decubitus was plausible.”
To pinpoint the DNA region that was triggering the condition, Dechow needed to not only genotype the recumbent calves, but also a group of unaffected relatives so that the different genome region could be determined between the two groups. The research was aided by the accurate genetic registry maintained by Holstein breeders internationally.
In the case of the recently discovered “haplotype”, which is a physical grouping of genomic variants along a chromosome that results in calf recumbency, 18 calves that exhibited the inability to stand in the neonatal period were genotyped and compared with 26 unaffected calves from the same family groups. Dechow and colleagues determined that the 18 affected calves carried two copies of a region on chromosome 16.
“What was different about this condition from most other known cattle genetic defects is that the mutation does not guarantee that the calf will be affected,” he said. “Some animals carry two copies of the mutation and are normal. Most, however, are not so lucky.”
The researchers traced the closest ancestor to a common bull born in 2008 that was present for both the paternal and maternal lineages of all affected calves. That sire had an influential son born in 2010 who is now one of the closest sires to the Holstein breed. Subsequent research has identified a bull born in 1984 as one of the first carriers, and perhaps the progenitor, of the mutation.
Dechow and his collaborators published the results in November 2022 in JDS Communications.
After determining the different genomic region, he needed to pinpoint the specific mutation within that region to develop a DNA test to identify other animals carrying the mutation. Dechow sequenced three animals with the help of bovine genetics company ABS Global to identify a mutation in a gene associated with calcium channels in muscle. Mutations in this gene are known to affect skeletal muscle function in other species, including humans.
Dechow devised a simple genetic test to identify Holsteins harboring the mutation. He and Penn State later applied for a patent and have worked with three companies to date to commercialize the technology. Farmers only need to send a few strands of hair, blood or tissue to the laboratory to find out if the animal from which it came is healthy, a carrier of the mutation or suffering from pressure sores.
For Dechow, solving a mystery through research, developing an innovative test, and then working with the private sector to commercialize the technology has been a rewarding process.
“It pleases me that we found it early enough, before it really exploded into a big calf welfare issue,” he said. “We detected this before a wave of calves were hit with decubitus and it would have been suppressed. I think we nipped this condition in the bud before it spread. I am also very grateful that our technology office has recognized the need to commercialize the DNA test quickly”.
DeChow expects the dairy industry to start using the test to aggressively select bulls that carry the mutant gene.
“In fact, it’s already started happening,” she said. “As a result, in a couple of years the frequency of the condition will be really low. In the long run, the lower frequency will mean that testing won’t be as much needed, but animals that are part of the artificial insemination industry will continue to be tested to ensure no hidden wearers are lost.”
CD Dechow et al, Identification of a putative haplotype associated with recumbency in Holstein calves, JDS Communications (2022). DOI: 10.3168/jdsc.2022-0224
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