‘Dark matter’ in cat genomes may shed light on human disease

While dogs are man’s best friend, cats are more genetically similar to humans than almost any other mammal, according to a researcher and her team at the University of Missouri. The findings, published today in Trends in Genetics, come from decades of genomic DNA sequencing by Leslie Lyons, a Gilbreath-McLorn-sponsored professor of comparative medicine at the MU College of Veterinary Medicine.

“Comparative genetics can play a key role in precision medicine and translational medicine, particularly in inherited diseases that affect both cats and humans, such as polycystic kidney disease and hypertrophic cardiomyopathy,” said Lyons. “Anything we as researchers can learn about identifying the causes of genetic diseases in cats or treating them can be useful in treating people with the same disease.”

As DNA sequencing technology has improved over time, Lyons and her team have created an almost 100% complete arrangement of the cat genome for mice or dogs.

Lyons explains that of the 3 billion DNA base pairs that make up the mammalian genome, only 2% of DNA is encoded in proteins that help our bodies perform natural functions. “Dark matter” DNA, or 98% of DNA with no apparent functions, can play a regulatory role in turning certain genes on or off, but this role is not fully understood by researchers.

“We want to find the regulatory elements in dark matter that may have specific DNA that turns our genes on or off, and since cats have a genome very similar to humans, dark matter is arranged in a similar way,” said Lyon . “By better understanding the cat genome, we can try to target and find these regulatory sequences and then possibly develop therapies that turn these sequences on or off. If we can turn off an entire gene, maybe we can turn off an entire cancer or disease that caused the genetic mutation in the first place. “

Lyon’s research improves animal welfare by discovering genetic mutations that cause disease. In a previous study, she found a specific mutation in a domestic cat in the gene responsible for Chediak-Higashi syndrome, a rare disease in both cats and humans that weakens the immune system and makes the body more susceptible to infection. Their research is also helpful in preventing hereditary diseases from being passed on to future generations.

“In most rare diseases, we get pretty good at finding genes where there is a single mutation that causes something good or bad, but the most common diseases in the general public, such as asthma, diabetes, obesity, high blood pressure, and allergies . are often more complex, ”said Lyons. “Since these are all common diseases that affect both cats and humans, more research comparing the feline and human genomes may one day help us understand what different genes and mechanisms work together to create these complex diseases.”

Lyons added that the COVID-19 pandemic underscores the importance of translational medicine. In addition to the coronavirus that causes COVID-19 in humans, it also causes infectious peritonitis in cats, which can be fatal.

“A few years ago we learned that the drug Remdesivir was effective in curing cats from infectious peritonitis in cats,” said Lyons. “When the pandemic started, we knew we could consider treating people with COVID-19 because the receptors for the virus are similar in cats and humans.”

More research is needed as questions remain to be investigated, Lyons said.

Leslie Lyons is a Gilbreath-McLorn-sponsored Professor of Comparative Medicine at the MU College of Veterinary Medicine.

“There is still a lot we don’t know, including why some cats get very sick and others don’t?” Said Lyon. “Why do some people die of COVID-19 while others show no symptoms? A better understanding of the cat’s biology and genetic makeup will help us to better understand human biology as well. “

Precision medicine will be a key component of the NextGen Precision Health Initiative, helping accelerate breakthroughs for patients in Missouri and beyond. Lyons is passionate about the role of feline genetics in precision medicine by laying the groundwork for tailor-made, specific treatments to suit the individual genetic makeup of the patient, whether the patient has two or four legs.

“Our overall goal is to make cats healthier by alleviating genetic problems and using this information to educate human medicine based on our findings,” said Lyons. “Our work can also help ensure that hereditary diseases in cats are not passed on to their offspring.”

“Cats – Telomere to Telomere and Nose to Tail” was published in Trends in Genetics today. Co-authors are William Murphy of Texas A&M and Wes Warren of MU.

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