Leslie A. Lyons

Leslie A. Lyons is an American geneticist. She is a professor of comparative medicine and the director of the Feline Genetics and Comparative Medicine Laboratory at the University of Missouri College of Veterinary Medicine. Lyons is one of the world’s foremost experts in feline genetics. Her work has advanced the understanding of the feline genome, highlighting its similarity to the human genome and its potential in precision medicine, which she frequently emphasizes while advocating for the use of cats as model organisms in genetic research.

Leslie A. Lyons
Nationality	American
Scientific career
Fields	Genetics
Institutions	University of Missouri, California National Primate Research Center

Career

In 1999, Lyons joined the Department of Population Health and Reproduction at the UC Davis School of Veterinary Medicine. In 2002, she analyzed the DNA of the world's first cloned cat, a kitten named Cc:, and confirming that it was indeed a true clone, a genetic copy of its mother.

Lyons has focused her research on heritable diseases and traits, as well as the population dynamics of domestic cats. She prioritizes specific conditions, including polycystic kidney disease (PKD), skin abnormalities, structural defects, and inherited blindness. Her earlier work involved using assisted reproduction techniques to create F1 and backcross cats between domestic cats and Asian leopard cats (Prionailurus bengalensis). She continues to collaborate with theriogenologists to maintain the biomedical model through gamete cryopreservation. Lyons has also conducted DNA studies for the first cloned domestic cat, wildcat, sand cat, and the GFP transgenic cat. Her laboratory has discovered nearly 50 mutations across more than 20 genes, which are linked to various diseases, coat colors, fur types, and cat AB/B blood types. Through her investigations of phenotypic traits, she has enabled cat breeders to enhance the efficiency of their breeding programs, ultimately benefiting feline welfare. Her studies in cat population genetics have clarified the genetic relationships among breeds and distinguished random-bred cat populations, reinforcing the idea that the Near East was the primary site of cat domestication. Research on ancient DNA from mummified cats indicates that today’s cats in Egypt are descendants of the felines that belonged to the pharaohs.

In 2013, Lyons joined the College of Veterinary Medicine at the University of Missouri and launched the 99 Lives Cat Genome Sequencing Initiative, with funding from the Winn Feline Foundation. This initiative aims to sequence cats with inherited diseases and provide a DNA variant resource for the research community. As of January 2016, her team had obtained DNA samples from 74 domestic cats and 9 wild felids, including lions and tigers, with close to 200 sequenced by November 2018. The initiative creates a comprehensive database of cat genomes, aiding in the investigation of genetic health issues, and their research has identified genetic causes for health conditions in cats. It aims to advance precision medicine for cats, providing more accurate diagnoses and tailored treatments based on genetic profiles. The Felid Taxon Advisory Group once informed the program about a widespread issue of black-footed cats (Felis nigripes) iin U.S. zoos going blind. Lyons and her team investigated and identified the genetic cause. The first case came from the Kansas City Zoo, and subsequently, other zoos across the country submitted samples for screening, preventing the birth of additional blind offspring. She has developed many genomic resources for felines, such as DNA panels for cat identification and parentage verification, a 63K DNA array, a new high-density array, exome capture arrays, and updated cat genome assemblies. The gene mapping resources derived from Geoffroy's cat and Asian leopard cats have now facilitated the creation of haploid-based phased genome assemblies for all three species, including a new reference assembly for the domestic cat. Lyons maintains significant collaborations with commercial animal genetic testing laboratories, as many of her tests are provided to the cat breeding community. Through the use of cat genetic testing, several genetic diseases in felines have been nearly eradicated, including polycystic kidney disease and blindness in Persian cats, hypokalemia in Burmese cats, spasticity in Devon Rex and Sphynx breeds, and blindness in Bengal cats.

In 2004, Lyons and her team discovered that the genetic mutations causing polycystic kidney disease occur in the same gene in both humans and cats. The finding opened new avenues for studying the disease, leading her to investigate other parts of the cat genome to understand their impact on the progression and severity of PKD. She has helped develop DNA tests for the disorder. Previous tests for this condition involved ultrasound scanning and were not very accurate, unlike the DNA test devised by Lyons. Approximately one third of all Persian cats carried the PKD gene at one time, but because of ultrasound testing and the newer, more accurate DNA tests, these PKD-carrier cats are gradually being identified and removed from the feline gene pool by spaying and neutering. A DNA test for feline coat color carriers and feline parentage has also been developed by Lyons, and is being offered to cat breeders, like the PKD test, so that they can determine whether cats they have bred have correct pedigrees, and whether these cats carry colorpoints, Burmese Colour Restriction, long hair, colour dilution or rare coat colors, such as chocolate and cinnamon.

Lyons has highlighted the underappreciation of cats in the scientific community and has advocated for their use as model organisms in genetic research. She argues that the feline genome is more similar to the human genome than those of dogs or mice, making cats valuable for studying genetic "dark matter" and diseases. She highlights that the cat genome is organized and conserved, akin to the human genome, which could aid in understanding complex genetic functions. Lyons also emphasizes the potential of cats in precision medicine, particularly for genetic diseases like polycystic kidney disease, suggesting that advances in treating such conditions in cats could be applicable to humans. She also underscores the importance of cat genomics in understanding the genetic basis of traits and diseases in both domestic and wild cat species, which can have broader implications for human health.

Although much of Lyons' research has dealt with cats, she also works on resources for gene mapping of other companion animals, such as dogs and horses, and has worked on the genetics of the rhesus macaque at the California National Primate Research Center.

In 2010, Lyons received the American Veterinary Medical Association/Winn Feline Foundation Research Award for her contributions to feline research.

Lyons holds 3 patents and has over 195 peer-reviewed publications. Her work has been featured in media, including a National Geographic Explorer episode titled "The Science of Cats" and several BBC productions on cats.

Selected publications

• Lyons, Leslie A.; O’Brien, Stephen J; Womack, James E; Moore, Karen J; Jenkins, Nancy A; Copeland, Neal G (February 1, 1993). "Anchored reference loci for comparative genome mapping in mammals". Nature Genetics. 3 (2). Nature Publishing Group: 103–112.
• Lyons, Leslie A.; Laughlin, Thomas F; Copeland, Neal G; Jenkins, Nancy A; Womack, James E; O’Brien, Stephen J (January 1, 1997). "Comparative anchor tagged sequences (CATS) for integrative mapping of mammalian genomes". Nature Genetics. 15 (1). Nature Publishing Group: 47–56.
• Lyons, Leslie A.; Menotti-Raymond, Marilyn; David, Victor A; Schäffer, Alejandro A; Tomlin, James F; Hutton, Michelle K; O’Brien, Stephen J (April 1, 1999). "A genetic linkage map of microsatellites in the domestic cat (Felis catus)". Genomics. 57 (1). Academic Press: 9–23.
• Lyons, Leslie A.; Shin, Taeyoung; Kraemer, Duane; Pryor, Jane; Liu, Ling; Rugila, James; Howe, Lisa; Buck, Sandra; Murphy, Keith; Westhusin, Mark (February 21, 2002). "A cat cloned by nuclear transplantation". Nature. 415 (6874). Nature Publishing Group: 859.
• Lyons, Leslie A.; Gómez, Martha C; Pope, C Earle; Giraldo, Angelica; Harris, Rebecca F; King, Amy L; Cole, Alex; Godke, Robert A; Dresser, Betsy L (September 2004). "Birth of African Wildcat cloned kittens born from domestic cats". Cloning and Stem Cells. 6 (3). Mary Ann Liebert, Inc.: 247–258.
• Lyons, Leslie A.; Biller, David S.; Erdman, Carolyn A.; Lipinski, Monika J.; Young, Amy E.; Roe, Bruce A.; Qin, Baifang; Grahn, Robert A. (October 1, 2004). "Feline polycystic kidney disease mutation identified in PKD1". Journal of the American Society of Nephrology. 15 (10). LWW: 2548–2555.
• Lyons, Leslie A.; Imes, David L.; Rah, Helen C.; Grahn, Robert A. (April 2005). "Tyrosinase mutations associated with Siamese and Burmese patterns in the domestic cat (Felis catus)". Animal Genetics. 36 (2). Blackwell Science Ltd: 119–126.
• Lyons, Leslie A.; Louwerens, Mathilde; London, Cheryl A; Pedersen, Niels C (May 2005). "Feline lymphoma in the Post—Feline leukemia virus era". Journal of Veterinary Internal Medicine. 19 (3). Blackwell Publishing Ltd: 329–335.
• Lyons, Leslie A.; Lipinski, Monika J.; Froenicke, Lutz; Baysac, Kathleen C.; Billings, Nicholas C.; Leutenegger, Christian M.; Levy, Alon M.; Longeri, Maria; Niini, Tirri; Ozpinar, Haydar; Slater, Margaret R.; Pedersen, Niels C. (January 2008). "The ascent of cat breeds: genetic evaluations of breeds and worldwide random-bred populations". Genomics. 91 (1). Academic Press: 12–21.
• Lyons, Leslie A.; Pedersen, Niels C.; Allen, Claire E. (December 1, 2008). "Pathogenesis of feline enteric coronavirus infection". Journal of Feline Medicine and Surgery. 10 (6). SAGE Publications: 529–541.