Identification of a novel deletion variant in the feline CMAH gene and its prevalence in Norwegian Forest Cats
This study identifies a novel homozygous three-nucleotide deletion (c.1052_1054delATC) in the feline CMAH gene associated with blood type B in a Norwegian Forest Cat and reveals that this variant is present at a significant frequency in the breed's population, suggesting it contributes to feline blood type diversity.
Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). This is an AI-generated explanation of a preprint that has not been peer-reviewed. It is not medical advice. Do not make health decisions based on this content. Read full disclaimer
Cats, like people, have different blood types. Most domestic cats carry type A, but some have type B, and a very few have a mix called AB. This difference is not just a label; it is a matter of life and death if a cat needs a blood transfusion. Giving a type B cat type A blood, or vice versa, triggers a dangerous immune reaction. The reason for these types lies in tiny chemical flags on the surface of the cat's red blood cells. In type A cats, the enzyme responsible for making these cells produces a specific sugar molecule called Neu5Gc. In type B cats, this enzyme is broken or missing, so the cells display a different sugar, Neu5Ac, instead. The gene that holds the instructions for building this enzyme is called CMAH. Scientists have long known that changes in this gene cause the shift from type A to type B, but the exact genetic instructions for why some cats have type B have remained a puzzle. While researchers have found several genetic typos associated with type B, they do not explain every case, leaving a gap in our understanding of feline biology.
A team of researchers set out to fill this gap by looking closely at the genetic code of a specific cat. They focused on a one-year-old male Norwegian Forest Cat, a breed known for its thick coat and friendly nature, who was registered as a healthy blood donor. When the team tested his blood, it came back as type B. To find the cause, they extracted DNA from his blood and read the entire sequence of the CMAH gene, comparing it against the standard genetic map for cats. They were looking for any differences, or mutations, that might explain why his enzyme was not working. They found that he did not carry the most common genetic change known to cause type B. Instead, they discovered something new: a tiny deletion in the genetic code. In the ninth section of the gene, three specific letters of the DNA code were missing. This small gap caused the cat's body to skip over a single building block, a leucine amino acid, when assembling the enzyme. Because the missing piece was just one block and the rest of the instructions remained in order, the enzyme was still made, but it was slightly shorter and likely misshapen, rendering it unable to do its job.
The researchers then asked a crucial question: is this tiny deletion a rare accident found only in this one cat, or is it a common trait hidden within the Norwegian Forest Cat breed? To find out, they gathered blood samples from 48 other Norwegian Forest Cats. Every single one of these cats had type A blood, which is the most common type for the breed. When the team checked their DNA for the same three-letter deletion, they found it in 13 of the 48 cats. These 13 cats were not type B; they were healthy carriers who had one working copy of the gene and one copy with the deletion. This meant that about 14 percent of the gene pool in this breed carried the variant. The researchers did not find any other cats in this group with two copies of the deletion, which would be necessary to produce type B blood. The fact that the deletion appeared in nearly a third of the cats tested suggests it is a common feature of the breed, even though it only causes type B blood when a cat inherits two copies.
This discovery helps clarify why the genetic rules for cat blood types are more complex than previously thought. The study shows that the loss of enzyme function can happen in different ways. In this specific case, the missing three letters of DNA were the only change found in the cat with type B blood, suggesting this deletion is the direct cause of his blood type. However, the researchers could not prove exactly how the missing amino acid breaks the enzyme, as current computer tools are not designed to predict the effects of this specific kind of genetic change. They also noted that other unknown factors might be at play, but the absence of any other genetic errors in the cat supports the idea that this deletion is the key. The findings highlight that different cat breeds may carry their own unique genetic variations that influence blood type. For veterinarians and breeders, this means that understanding blood type requires looking beyond the most common genetic markers, as rare or breed-specific changes could be the reason behind a cat's blood type. The study expands the list of known genetic causes for feline blood types and reminds us that the genetic landscape of cats is diverse and still being mapped.
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