The widespread use of popular sires can lead to genetic defects in offspring, but the defects aren’t always obvious until generations later. When several New York dairy farmers noticed newborn calves that couldn’t rise and stand after birth, they were facing a mystery.

The farms’ veterinarians had done blood work on live calves and necropsies on calves that didn’t survive, but nothing stood out. One herd that was doing IVF for more valuable calves conducted extensive testing to figure out what was wrong with newborn calves that couldn’t stand.

“There was another calf from a different farm that had issues,” said Chad Dechow, associate professor of dairy cattle genetics, Penn State. “I started asking people if they had seen it and there were two additional farms. In one case there were quite a few calves from one particular IVF mating. They had several embryos from that mating and a reasonably large proportion of calves showed this condition.”

Dechow said the difference in this issue compared to calves with obvious physical deformities is that affected calves appear to be entirely healthy other than the inability to stand up. He noted that farms have different tolerance levels regarding how much they’re willing to work with an animal to help it recover, so some farms were able to save calves by helping them get up and nursing them to recovery.

After finding no obvious answers, a New York veterinarian contacted Dechow in autumn 2020 regarding the issue. Vets were aware of Dechow’s work regarding the genetic aspect of a cholesterol deficiency in dairy cattle, so they hoped he could provide insight from that angle.

“Vets had already done exhaustive testing on calves with the condition,” said Dechow. “They were saying ‘If it isn’t genetic, we don’t know what it is.’”

It wasn’t obvious at first that the issue was genetic. When farmers with affected calves first contacted Dechow, he requested tissue samples for possible future genotyping. “In many of the first calves affected, the farms were doing a lot of IVF fertilization,” he said. “One of the farms had been working with the organization doing their IVF to see if something went wrong in the IVF process.”

Further investigation showed that some of the calves, including some from natural service and traditional AI, showed signs of having the problem, so IVF was eliminated as the cause.

Untangling a genetic defect

Genetic testing now can help both breeders and producers try to avoid early onset muscle weakness syndrome in Holstein calves. Photo by Courtney Llewellyn

What’s different about this condition, and something that’s similar in humans with the same genetic issue, is that some people can have the mutation and never express it. “That’s one of the trickier parts of this,” said Dechow. “The penetrance of the condition is not 100% – we don’t really know what the penetrance is. Some animals are perfectly normal but have the genetic basis for it, and we don’t know why at this point.”

As he worked to unravel the possible genetic connection, Dechow’s best guess was that the defect traced to 1984 and a sire named Southwind Bell of Bar-Lee. “A mutation occurred, probably in the late ‘70s or early ‘80s, which had a low frequency,” said Dechow. “Some animals had it but we never knew about it. After the mutation was amplified because of a popular pedigree, it became apparent there was a problem.” He said the defect wasn’t apparent in the ‘80s, with only random and rare incidences of the issue.

At first Dechow referred to the defect as “motor inability” but that wasn’t a good term because it implied a neurological condition. “Muscles are stimulated by nerves,” he said, “so a neurological issue could cause the same clinical signs. But that turned out to not be the case.”

The condition was eventually labeled calf recumbency, and now the genetic defect is referred to as early onset muscle weakness syndrome (MW).

“The mutation was in the [Holstein] population at a very low level until Roylane Socra Robust, a fairly popular bull that has several sons in AI,” said Dechow. “One of those sons is Seagull-Bay Supersire. That bull was extremely popular and is currently one of the most highly related bulls in the Holstein cow population. Those two bulls amplified the mutation that had been around for a while, and many of their descendants are carriers.”

Several bulls have been homozygous for the condition, but to Dechow’s knowledge, none of the widely used older sires such as Elevation and Ivanhoe are sources of the mutation.

Dechow said time between when the defect was first reported to identifying the genetic mutation was less than two years. “We were able to do it pretty quickly because of genomic testing,” he said. “The problem was sampling enough calves with the condition. Once I reached that number – about 18 calves with the condition – the actual ability to find the chromosome where the condition is located took several months.”

Dechow added that locating the mutation within the chromosome took a little longer because it required the expensive process of whole genome sequencing.

As he continued researching the issue, he used established techniques to discover the mutation. Since this mutation affected quite a few calves and is still present in the breed, Dechow believes the dairy industry will be more focused on reporting issues as they occur to more quickly identify carriers.

In the early stages, there were likely far more calves with the mutation, but they showed up as a random calf that had something wrong and no one thought a lot about it. “I suspect there were hundreds that had it here and there, and some recovered,” Dechow said. “Unfortunately, it took a herd that had quite a few of these calves to consider something was seriously wrong.”

The potential welfare issue of calves not able to stand at birth is a concern, but thanks to genetic testing, Holstein breeders can make sure a heifer with two copies of the gene is not bred to a bull that will result in an affected calf. Holstein breeders whose goal is to market superior genetics are likely aware of the issue.

“Commercial dairymen might not be aware,” said Dechow, “but the good news is that because there’s a genetic test, there isn’t a big risk it will explode in their herds because most of the bulls they use will be mostly free of the condition. There will be some real good bulls that are still available and are carriers of the condition, but we’ve started to reduce the frequency.”

by Sally Colby