Friday, April 26, 2024

I tested my cat’s DNA, but the results only led to more more mysteries

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At the first modern cat show, which took place in London in 1871, the stars — more than 150 of them — snoozed on crimson pillows positioned in luxuriously close proximity to saucers of milk. If they were too lethargic, women would poke them with their parasols. There was a lot of variety, but only a few recognizable breeds, like the Persian and the manx. One attendee called the Siamese, which were new to the country, an “unnatural, nightmare kind of cat.”

The show and those that followed did much to raise the profile of the cat in England, where children were taught “that cats are treacherous, that they are thieves by nature and incapable of honesty, that they have no real affection for master or mistress, and love the places where they live far more than the people who own them,” according to Gordon Stables, who wrote about felines.

Harrison Weir is often credited with popularizing cat shows. He and his brother even managed to get Charles Darwin as a patron for one. (Darwin did warn that “people may refuse to go and admire a lot of atheistical cats!”) As the shows grew, both Weir and Stables attempted to herd cats into some semblance of breeds, though they mostly relied on color, as well as coat length, to distinguish them: tortoiseshells, tabbies that were blue or silver, brown, red, black, white, or black and white. In the decades that followed, specialty cat groups, like the Silver and Smoke Persian Cat Club, started forming. Of the between 42 and 71 cat breeds recognized by various associations, 16 are considered “natural” or “foundational.” These include Maine coon, Abyssinian, Persian, and Russian Blue. More modern breeds, like Bengals and Ragdolls, are less than 100 years old and were created by people purposefully selecting for traits.

Well spotted

Anthony Hutcherson has been breeding Bengal cats for decades. “It’s like having a little bit of the Amazon rain forest in your house every day,” he told Digital Trends. The first Bengals began as part of a leukemia research program in the 1970s, when Loma Linda University pediatrics professor Dr. Willard R. Centerwall bred wild Asian leopard cats with domestic cats. Jean Mill received some first-generation offspring from these pairings, which she then bred with her own domestic cat. Even several generations in, Bengals retain their leopard-like spots and love of water. They “occasionally saunter in as you take a shower,” Hutcherson said.

The Begal cat is a hyrbrid breed of cat created from domesticated cats and the Asian leopard cat. Rosalina Stevens/Getty Images

Starting out, Hutcherson wanted a pet leopard but quickly realized his family and neighbors wouldn’t appreciate bunking so close to a wild animal. He moved on to ocicats, which are a completely domestic mix of Siamese, Abyssinian, and American Shorthairs. Cat coat colors and patterns are controlled by a number of genes, so it’s possible to end up with an ocicat that’s solid instead of spotted. Trying to minimize the number of offspring who looked more like panthers than ocelots required pedigrees, charts, and test litters. “That was a lot of cats and a lot of cat litter and cat food and effort to find out things that modern science now allows us to find out with a cheek swab,” said Hutcherson.

In 2007, a four-year-old Abyssinian cat named Cinnamon had her genome partially sequenced. Since then, researchers have learned a lot about cat DNA, despite funding challenges. “There’s been less funding for cats than there is for dogs, and mainly this is driven by the fact that there are a lot more dog breed than are cat breeds,” said Dr. Leslie Lyons, one of the foremost feline-only geneticists. (Her lab’s nickname is the Lyons Den, so she’s probably already heard any joke about her name you can think of.) She started the 99 Lives project to sequencing the genomes of a wide variety of cats. They’ve already reached over 200. Ten years after Cinnamon’s first sequencing, Lyons’ lab put out an expanded, improved genome for her.

“It’s like having a little bit of the Amazon rain forest in your house every day.”

Conditions including asthma, retinal atrophy, and polycystic kidney disease have similarities in humans and cats. “If we have 21,000 genes in the human body, a majority of those are the same genes that are found in cats and dogs and pigs and horses, as well,” said Lyon. “So most all mammals have about the same size genomes and they have the same genes. They’re very similar to one another. So the gene that causes polycystic kidney disease in the cat is the same gene that causes polycystic kidney disease in humans.”

Scientists have also found out a lot about cats’ appearance, like the mutation that causes the Cornish Rex’s curly, poodle-esque coat. While a “tameness” gene may exist for certain foxes, it’s still unclear what makes Ragdoll cats go floppy in your arms or the manx so playful. Breeders still favor cats with certain personalities and traits, hoping they’ll get passed on. As an episode of This American Life shows, even creating a clone won’t guarantee an animal will be as loving or good-natured as its predecessor.

Recently, the Lyons Feline Genetics Research Lab at UC Davis discovered a recessive mutation that causes the curly coat in Cornish Rex cats. Romas Zeimys/Getty Images

For Hutcherson, the goal is to keep the look of the Asian leopard cat without its less-than-domesticated behaviors — like urinating all over the house. “Anybody who’s ever been to a zoo has seen lions and tigers and ocelots and cougars pace back and forth for hours,” he said. “Leopard cats do that as well.”  When he’s choosing a cat to breed, he’s selecting against those behaviors, looking for cats that are fine spending more time on the couch and less time on patrol. As he hopes to make Bengals more wild on the outside and tame on the inside, Hutcherson is embracing genetic testing to eliminate diseases, enhance diversity, and select for specific traits. But he’s mindful that tweaking genes doesn’t happen in isolation. Sometimes unwanted side-effects occur. “I recognize both the value and the potential harm that these identifications can make, because there had to be something wonderful about an African wildcat that made people want to live closer to it made somebody want to pick it up and feed it and play with the kittens,” he said.

Well bred

The pursuit of the perfect collection of traits can cause unfortunate outcomes. The beloved look of frying-pan faced cats, including Persians, has led breeders to select for shorter muzzles. A condition called Brachycephalic Obstructive Airway Syndrome, which causes breathing problems, is the result. Despite knowing the associated risks, Hutcherson said he was horrified to see veterinarians cooing over squashy-faced entrants at cat shows. Creating newer breeds, like toygers, can result in extremely mutated offspring.

Hutcherson was horrified to see veterinarians cooing over squashy-faced entrants at cat shows.

There are genetic tests that can help guide breeders to keep more diversity in their lineages and avoid some of the test matings that used to be required to find out which traits a cat was dominant and recessive for. Thanks to feline genetics research, breeders can also avoid mating two cats that would result in kittens with certain diseases, like retinal atrophy, which causes blindness.

Mars makes Twix, Skittles, Pedigree pet food, and the Optimal Selection DNA tests for cats and dogs. The tests are aimed at breeders, using the same type of genotyping as kits like 23andM3. It provides information on animals’ coat color, pattern, and type (there are several varieties of long fur), as well as other physical morphologies, like Japanese bobtail and manx tail mutations. There are also over 40 types of diseases the panel tests for. It also tells owners the cat’s blood type and gives them a diversity percentage.

Optimal Selection

The percentage is based on the ratio of heterozygous genes, ones where the cat inherited two different alleles from its parents. Optimal Selection plots the percentage on a graph. If the number is further to the left, the cat isn’t the most diverse of its breed and should ideally pair with a cat who’s more genetically diverse, whose percentage falls further to the right. “The idea is for the breeders to shift that curve more and more to the right by increasing the genetic diversity available in their population,” said Dr. Angela Hughes, veterinary genetics research manager at Wisdom Health, maker of Optimal Selection. Some breeds are required to have very specific characteristics, though. There’s no Russian blue without the signature, lustrous silver coat.

How a breed is fairing, diversity-wise, depends on a lot of factors. “Many cat breeds started with one individual or a very small population,” said Dr. Katie Lytle, a veterinarian and professional channel manager at Wisdom Health. Even a breed that’s been around for ages, the Siamese, has a median heterozygosity of 24.1 percent. The median for all pedigreed cats is 33.6, and for random-bred it’s 38.7 percent. The company has a tool to help breeders find better matches for their cats, and it can also predict how genetically diverse the offspring will be.

“Many cat breeds started with one individual or a very small population.”

Knowing a cat’s blood type and if it’s a carrier for diseases is essential for breeders. But what about the average pet owner whose cat is definitely not going to have any kittens? “One of the things that we worry about with cats is sort of a silent heart disease, hypertrophic cardiomyopathy,” said Lytle; it’s one of the diseases Optimal Selection tests for. “A bad day in veterinary practice is when you lose a patient unexpectedly.” It’s somewhat common in Maine coons, but what if you have no idea what type of cat you have? The American Society for the Prevention of Cruelty to Animals estimates only around three percent of cats in the U.S. come from breeders. The rest are random-bred — domestic short-hair, long-hair, or medium-hair kitties without pedigree or papers.

If I had to guess the breed of my cat Dobby, I’d say nebelung. Google Lens, which can apparently identify breeds, agrees with me. He has long, sleek, silver fur and trots around after me like a puppy. He ended up at a shelter a couple years ago, along with his littermates who looked nothing like him. Dobby and his brothers and sisters are possibly the result of heteropaternal superfecundation — meaning females can be impregnated by multiple males, resulting in litters full of half-siblings.

Well born

Basepaws is a cat DNA test that gives you “findings about your cat’s breed,” but emphasizes that it isn’t a breed test. It’s not going to tell you that your cat is 50 percent Persian, 25 percent Ragdoll and 25 percent Birman. It also won’t tell you anything about what diseases your cat is carrying, though Basepaws says that information will come in the future. “[With] recent issues, the mistakes that companies are making, we’re being very careful about overstating our findings and being very, very cautious about what we release,” Anna Skaya, the company’s CEO, said.

Using Basepaws’ two packing tape-like strips, I removed some silky tufts of fur from Dobby’s back. The website said I’d have my results in eight to 10 weeks, though it actually took about five months. According to my report, Dobby is similar to Burmese, Siamese, Persian, Ragdoll, Peterbald, LaPerm, Japanese Bobtail, Himalayan, Egyptian Mau, British Shorthair, and American Shorthair. Each breed had its own graph, plotting from less likely to more likely, with domestic in the middle. The width of the bar on the graph “indicates the exactness” of the test’s prediction. Dobby’s bars were similarly sized for the most part and hovered around the middle, with the ends going towards both “more likely” and “less likely.” It was confusing. My husband, who’s a scientist, interpreted it as if Dobby isn’t a domestic, there’s roughly between a 25 and 82 percent chance he’s a Burmese.

Jenny McGrath/Digital Trends

Within a couple months of getting the results, Basepaws updated the report. Now his ancestry is broken down into groups: 33.21% Western, 21.40% Eastern, 8.61% Hybrid, and 36.78% Polycat. Polycat isn’t really a designation; it’s Basepaws’ own term for domestic, non-pedigree cats. Several researchers have shown that breeds fit into different groups. If you create a plot with Eastern origins on the left, Western origins on the right, and Mediterranean in the middle, you’ll see certain breeds cluster together along the graph.Siamese, Burmese, Korat and Birman skew Eastern, while Persian, Selkirk Rex, British Shorthair, and Scottish Fold are all the way on the other side, the Western breeds. In the middle are the Mediterranean cats, Turkish Angora and Turkish Van. A study also found that non-pedigree, domestic cats from Vietnam, China, Korea, and Singapore were very similar, genetically, to Eastern-associated breeds such as Burmese, Siamese, and so on. Meanwhile, domestic American cats were similar to non-pedigree cats found in Western Europe, but Italian cats had both European and Mediterranean characteristics.

The report also gives three breeds that Dobby is the most similar to. Although overall he has a higher percentage of Western in him, his most similar breed is (still) Burmese, an Eastern breed. (Basepaws knows this isn’t intuitive.) Basepaws ditched the graph for some chromosome maps. The main one shows 18 chromosome pairs with regions highlighted different colors for sections that are Western, Eastern, and so on. For the individual breeds Dobby is similar to, the Burmese, Oriental Shorthair, Birman, and Siamese sections on some unlabeled chromosomes are shown. Per the report, Dobby is more similar to Burmese than 98.79 percent of the cats in Basepaws’ database. His results weren’t nearly as high for the other three breeds: 21.82 percent for Oriental Shorthair, 8.15 percent for Birman, and just 2.07 percent for Siamese.

Without the health data, there doesn’t seem to be much point in telling my vet that Dobby might have some Burmese traits.

It’s interesting, but it isn’t all that helpful. With a mix like that, my cat certainly isn’t entering any cat shows. Maybe Dobby really is a secret Nebelung, but that’s not one of the breeds Basepaws has in its database. There are currently 21 breeds, though it is working on adding six more. But also, without the health data, there doesn’t seem to be much point in telling my vet that Dobby might have some Burmese traits. While it’s nice to confirmation that the breed is dog-like in their tendency to follow owners room to room, but I’d prefer to know if he has hypokalemia, a disease known to affect Burmese cats. (Actually, thanks to his Optimal Selection test, I know he’s in the clear for it and all the other diseases tested, though he is a carrier for a blood-brain barrier dysfunction disorder that may cause certain drugs to be more toxic.)

Basepaws isn’t terribly open about its database. To start, it used publicly available databases of cat genomes, then contacted breeders. For the $95 price, the company isn’t sequencing your cat’s whole genome (thought it says it can for an extra fee). .) “Our methodology tries to get the best of both targeted and broad-range sequencing by combining low coverage sequencing and target specific sequencing,” according to a document the company sent to Digital Trends. “While this method will yield enough data for breed identification and specific diseases/traits, we do not foresee it being enough for downstream novel variant discovery.” Basepaws is working on technology that will help them discover these new variants, which it will then use to try and sell you special cat food: “Personalization in pet nutrition is our first goal.”

Well made

There are a few ways to genetically differentiate breeds. One is with short tandem repeat (STR) markers, which measures the number of repeats at a certain position on a chromosome in two samples. Single-nucleotide polymorphisms are locations in DNA sequences with uncommon variations. Both can be used to determine breeds, though sometimes cats are so genetically similar that researchers will have to look for other traits. Take the tailless Manx. “A long-haired version of a Manx is called a Cymric,” said Lyons. “Genetically they’re the same cat but they have one genetic difference and that’s long versus short hair.” Many new breeds are these single-gene variants, with only a change in fur length, pattern, or color from the founding breed.

“Random bred cats are the original populations from which the breeds developed, not a population of pedigreed cats gone feral,” Dr. Jennifer Kurushima wrote in her study of domestic feline genetics. That’s the opposite of dogs, which have had hundreds of years to become distinct breeds. The average Rover from the animal shelter might be part lab, part retriever, part German shepherd, and the genetic markers distinguishing them are easier to tell. In contrast, a Havana cat was developed from Siamese lineages, but Siamese are very similar to the domestic cats found in the Eastern group.

Basepaws’ Wild Cat Index compares your cat’s DNA sequence to an assortment of wild cats to help identify which ones your cat may be related to compared to others they have tested. Basepaws

The second part of Basepaws’ report is a “Wild Cat Index.” In the first version, Dobby was more like scimitar-toothed cats than 98 percent of cats tested, more like leopard cats than 82 percent of the database, and varying percentages for 12 other big cats. (He was more similar to lions than zero percent of cats, so he’ll just have to wait to be king.)  The newer report gets rid of the majority of those species and just focuses on leopards, cougars, tigers, and cheetahs and how similar their genomes are to your cat’s. Right now, the report just ranks them, one to four, without giving any other information. Skaya compares it to 23andMe’s Neanderthal report.

“Genetically, it has been demonstrated that the North African wildcat, which is also present in the Near and Middle East, Felis silvestris lybica, is the ancestor of all domestic cats,” Dr. Claudio Ottoni, told Digital Trends. A couple years ago, he published a paper on using DNA analysis to trace the domestication of cats. Five subgroups of Felis wildcats, distributed in areas including Europe, Southern Africa, and China, are the closest relatives to the domestic cats. These wild populations sometimes still intermix with feral cats and are genetically similar enough to produce fertile offspring.

“Cats were most likely never selected for a peculiar task by human.”

In 2001, archaeologists uncovered a 9,500-year-old burial site in Cyprus that contained both a human and a kitten. Researchers believe cat domestication started around 10,000 years ago, and the internment suggests the animal may have been a pet. Because cats aren’t native to the island, it’s likely humans introduced them. The domestication likely began in areas encompassed by the present-day Middle East, especially in agricultural communities. “Cats were most likely never selected for a peculiar task by humans,” said Ottoni. “They already possessed in their wild state the predatory skills that made them useful to human communities: hunting mice and rats that were attracted by grain storages.” That’s in contrast to dogs, goats, and cows, which were bred for specific occupations.

Still, something had to change to move cats out of the barn and into the home. “In our study, we speculate that this change in behavior might have occurred in Egyptian cats, where the peculiar social and cultural context of the Egyptian society (cats were venerated and kept in households and temples) favoured the emergence of such more sociable traits,” said Ottoni. There’s evidence that humans were caring for cats as far back as 4,000 to 6,000 years ago. Studying the mitochondrial DNA of 200 ancient cats, Ottoni found felines from 6,400 years in Southeast Europe with genetic links to the Near Eastern group. “A subsequent, second wave of cat dispersal started most likely from Egypt during Classical Antiquity and led to the diffusion across time of a peculiar African genetic lineage as far as Northern Europe and later the Old World,” he said. The Roman army and ship captains helped cats spread even farther.

For $95, Basepaws didn’t really unlock any mysteries of Dobby. I still don’t know why he insists on jumping on top of my bookshelves and knocking everything to the floor. Why is he so obsessed with robot vacuums? There probably isn’t a DNA test in the world that could tell me. However, if you’re really curious about where your cat comes from, University of California, Davis has an ancestry test for $120 that helps support research instead of trying to get you to buy fancy pet food.

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