AT Update CA NESTLÉ PURINA PUBLICATION DEDICATED TO CAT ENTHUSIASTS VOLUME 17 | FALL 2019
99 LIVES CAT GENOME SEQUENCING INITIATIVE Aids Discovery of Feline Disease Genes FALL 2019 99 Lives Cat Genome Sequencing Initiative HELPS TO ADVANCE DISCOVERY OF DISEASES AND TRAITS
Research of feline genetic diseases fessor of Comparative Medicine and traits got a huge boost in 2015 at the University of Missouri, who when the 99 Lives Cat Genome began the 99 Lives Initiative, says, Sequencing Initiative was founded. “The idea was to include all breeds The purpose was to build an in-depth, and cats from around the world — accessible genetic database of those that are healthy as well as domestic and wild cat species that those with health concerns.” researchers could use to investigate Thus far, donated DNA samples heritable diseases. Many studies have from more than 200 domestic cats “We found that glitter is benefited from having a handy — including 37 pedigree cat breeds caused by a mutation in source of DNA. and crossbreeds — and 21 wild cats Geneticist Leslie Lyons, PhD, the representing 15 wild cat species a gene called fibroblast Gilbreath McLorn Endowed Pro- have been whole-genome sequenced. growth factor receptor 2, which regulates the growth and structural composition of hair in cats and other mammals.”
Chris Kaelin, PhD, senior scientist at Stanford University and HudsonAlpha Institute
CH Jungletrax Orange Fanta C, a glittered brown-spotted tabby female Bengal kitten, COVER PHOTO BY STARRLIGHT PHOTOGRAPHY was bred and is owned by Anthony Hutcherson. 2 CAT Update
“Currently, there are 56 principle investigators at 43 institutions, companies and zoos contributing to and using data to study about 200 diseases and phenotypes,” Dr. Lyons says. “There are about 52 cats involved with cardiac disease studies, plus there are 21 neurological studies, four behavior studies, five urinary studies, and many others as well.” Research tied to the 99 Lives Dr. Chris Kaelin, studying a strand of glittered hair coat, identified the mutation Initiative stood out among the for the coat color anomaly using data from feline presentations at the 10th the 99 Lives Cat Genome Sequencing International Conference on Canine Initiative. and Feline Genetics and Genomics was independently introduced by held in May 2019 in Bern, Switzerland. multiple, dierent Asian leopard The scientific meeting, attended by cats during Bengal breed devel- 200 research scientists and graduate opment. The Asian leopard cat students from 20 countries, was allele works less eciently when sponsored by Purina. swapped in a domestic cat and the At the Bern conference, Chris result is a dark, Zorro-like appearance.” Kaelin, PhD, senior scientist at A Bengal breeder who has donat- Stanford University and Hudson- ed more than 100 DNA samples to Purina has sponsored the Alpha Institute, told how his team genetic studies, Anthony Hutcher- tapped into the 99 Lives Initiative son of Jungletrax cattery in Port International Conference to find the mutation that causes a Tobacco, Maryland, helped Dr. Kaelin desirable coat trait in Bengal cats discover the glitter variant. His cat, on Canine and Feline called “glitter.” They also added to RW SGC Jungletrax Flowmaster, Genetics and Genomics what was known about a distinctive carried the gene insertion and was Bengal trait called “charcoal.” part of the study. since its beginning in 2002. Bengals are known for the beauty “When ‘Flowmaster’ sits in the of their ornate color coat patterns sunshine, he glows like he’s plugged The 10th meeting of the reminiscent of the spotted coat into an electric outlet,” says Hutch- group of research scientists of the Asian leopard cat that was erson, a member of the board of crossed with domestic cats 35 years directors of Winn Feline Foundation was held in May 2019 in ago to create the popular breed. and The International Cat Association. In some Bengals, a bonus sparkling “Glitter comes from a single domestic Bern, Switzerland. or iridescence – the glitter eect cat, Millwood Tory of Delhi, used to — adds a lovely sheen to the coat. create the Bengal breed. A home- Meanwhile, the charcoal trait gives less cat in India added one of the some Bengal cats markings like most beautiful and unique traits in Zorro, with a white goggle look our breed.” around the eyes and a cape eect Winn Feline Foundation, a non- that extends down their back. profit organization that supports “We found that glitter is caused by exclusively feline medicine research, a mutation in a gene called fibroblast has funded the 99 Lives Cat Genome growth factor receptor 2, which Sequencing Initiative since the regulates the growth and structural beginning, as well as its predecessor, composition of hair in cats and the 9 Lives Cat Genome Sequencing other mammals,” Dr. Kaelin says. Project. Both have evolved from “Extending work done previously completion of the feline genetic map by Dr. Lyons and her colleagues, in the fall of 2005, which was we showed that the charcoal allele developed using an Abyssinian cat 3 FALL 2019
Whole-genome sequencing enables an individual cat’s entire genetic blueprint to be analyzed for changes to the genetic code. The feline genome is made up of 2.5 billion coding units, consisting PHOTO BY STARRLIGHT PHOTOGRAPHY BY STARRLIGHT PHOTO of four nucleotides denoted by the letters A, T, C and G. These dierences are then compared to see if any may be linked to a certain disease or trait. Among the successes that have come from researchers using the 99 Lives feline databank, Dr. Lyons, who also presented at the Bern genomics conference, gives credit to the discovery of dierent gene mutations for progressive retinal atrophy in Persians, Bengals and South African black-footed cats, myopathy in Devon Rex, lymph- adenopathy in British Shorthairs, and the tail mutation in the Japa- nese Bobtail. Work underway involves a com- plicated study to identify cats at risk for feline infectious peritonitis (FIP), with a goal of ultimately helping clinicians determine whether cats exposed to the virus will develop disease. The most important viral disease in cats under 3 years of age, FIP is caused by a mutant form of a highly contagious but RW BW SGC SimplyBlessed Arctic Summer, named “Cinnamon.” In 2005 there common virus in cats’ intestinal bred and owned by Beth and Lori Bearry, is the first longhaired Bengal to be named were about 1,680 markers. tract, feline enteric coronavirus a Supreme Grand Champion by The Inter- “Our DNA array has 63,000 mark- (FECV). The mutation that causes national Cat Association. ers, and many have been mapped FIP is believed to occur in individ- in cat pedigrees,” Dr. Lyons says. ual cats that cannot fight o the “The cat genome is now one of new type of infection, commonly the best for any species, except aecting kittens and cats with mouse and man.” weak immune systems. “The 99 Lives Initiative makes it quicker, easier and cheaper to find EARLY PRA DISCOVERIES DNA variants that cause significant Among her own breakthroughs, disease,” says Vicki Thayer, DVM, Dr. Lyons discovered the dierent DABVP (feline), former executive autosomal recessive gene mutations director of Winn Feline and current causing progressive retinal atrophy member of the board of directors. (PRA) in Bengals and Persians, “Over the past three decades Winn projects that took place over a Feline has funded genetic feline decade and through her moving diseases, there certainly have been from the University of California- a lot of ‘wins’ along the way.” Davis to her current position at the 4 CAT Update
99 LIVES CONSORTIUM FELINE GENETIC DISCOVERIES
Disease or Trait Status
Progressive retinal atrophy DNA test available via the University (PRA) in Bengals of California-Davis Veterinary Genetics Laboratory “With PRA, I would like to be at the point where we PRA in Persians DNA test available via the University of California-Davis Veterinary Genetics could correct vision by Laboratory & research published in BMC Genomics putting a corrected version
PRA in South African Research published in Scientific Reports of the gene into the black-footed cats in 2017 & in 2018 photoreceptor of the eye.”
Niemann-Pick Type C1 Variant identified & research published Leslie Lyons, PhD, Gilbreath McLorn (neurological condition) in in March 2017 in the Journal of Veterinary Endowed Professor of Comparative American Shorthairs Internal Medicine Medicine, University of Missouri
Japanese Bobtail short-tail Variant identified & research published gene mutation in BMC Genomics
Retinal degeneration in black- Variant identified footed cat (felis nigripes)
Lil’ Bub celebrity cat with Variants identified & research published osteopetrosis and poly- online in 2019 in bioRxiv dactylism causal mutations identified
Dwarfism in Munchkin cat Variant identified breed
Macular degeneration Variant identified
Hydrocephalus in Orientals DNA test available and Toygers
Amyloidosis in Abyssinians Variants identified
Chediak-Higashi syndrome Variant identified (albinism) in Persians
Epilepsy Variants identified
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University of Missouri. An inherited Veterinary ophthalmologists eye disorder, PRA causes degen- suspected that Idle Chatter could eration of the retina, eventually have PRA. “We were heartbroken leading to blindness. Located at when he was diagnosed at 8 months the back of the eye, the retina takes old and then went blind between 12 the light gathered and focused and 14 months old,” says Beth Bearry. by the eye’s rods and cones and Dr. Lyons began studying Idle converts it into electrical nerve Chatter’s genetics. First, she and signals, sending it on to the optic her team ensured that the cat’s PRA nerve and then the brain for inter- was not due to a dietary taurine pretation. deficiency or antibiotics, both of An early-onset PRA in Persians which can cause blindness. Working progresses rapidly in kittens and with Beth and Lori Bearry, through causes blindness by 12 to 16 weeks repeat breedings of the tom and of age. In Bengals, the disease queen, they found that some of the occurs later and is slower progress- kittens became blind, indicating ing, with vision problems starting an inherited link. around 4 to 5 months of age and “We recognized this as a recessive resulting in severe visual impairment. trait, but then we needed to know Bengal breeders Beth and Lori how and why PRA developed in Bearry of Simply Blessed Bengals Bengals,” Dr. Lyons says. in Jackson, California, recall visiting The gene variant discovery finally the University of California-Davis came in 2013 — through the 9 Lives Veterinary Medical Teaching Hospital Cat Genome Sequencing Project. with their 6-month-old kitten named Dr. Lyons, who had now moved Idle Chatter and thinking he may her laboratory to the University have developed cataracts because of Missouri, had access to the they noticed his eyes glowed. “He whole-genome information would pace back and forth as eve- of 10 cats. “We sequenced the ning fell,” Beth Bearry says. “When DNA of a trio of cats and performed it got dark outside, he would find a comparative, genome-wide a safe place in our house to stay association study,” she says. “This until morning.” narrowed the PRA defect down to one chromosome and one region on that chromosome.” FELINE DNA NEEDED FOR 99 LIVES Although several variants were CAT GENOME SEQUENCING INITIATIVE possible in Bengals, three gene mutations discovered previously The research team at the University of Missouri is in Abyssinians and Persians were seeking DNA samples from 16 cat breeds and from cats with particular not it. Neither was the first DNA feline diseases. Breeds in which DNA is needed are: American Bobtail, variant they studied in Bengals. Balinese, Bombay, Burmilla, Cornish Rex, Chausie, Exotic Shorthair, “A blind cat showed us a second Khamomanee, Kurilian Bobtail, Manx, Norwegian Forest Cat, Russian variant in a gene never known Blue, Singapura, Somali, Thai, and Turkish Van. before to cause blindness, which They are looking for DNA from cats diagnosed with inherited cancers: turned out to be key in Bengals,” lymphoma, fibrosarcoma, squamous cell carcinoma, melanoma, and Dr. Lyons says. mammary cancer. They also are seeking DNA from these cats with Findings of the gene variants for unusual coat phenotypes: Peterbald, Don Sphynx and American Wirehair. PRA in Bengals and Persians were For information contact Dr. Leslie Lyons at the University of Missouri developed into genetic tests at at [email protected]. For information about the cancer studies, the University of California-Davis contact Dr. Wesley Warren at [email protected]. Veterinary Genetics Laboratory.
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Cat Update articles may be reprinted provided the article is used in its entirety and in a Jungletrax Scion Affinity Marquee is a Bengal male bred by Anthony Hutcherson. positive manner. If you are inter- ested in reprinting this article, Cat breeders have been able to of the eye. This would take over please contact the editor at: order genetic testing kits since and make the right proteins and [email protected]. 2015, enabling them to identify do what is necessary for normal com. Reprints should include carriers and breed away from the vision. We are just at the tip of the following attribution: Used disease. In an autosomal recessive the iceberg.” with permission from the Cat disease, an aected cat inherits the Reflecting on the progress that Update, Nestlé Purina PetCare. gene mutation from both the queen has been made thanks to the 99 and tom, which are carriers and Lives Initiative, particularly related have one copy of the PRA variant. to how it impacts cat breeders, All of the cats at the Simply Hutcherson, who attended the Blessed Bengals cattery have genomics conference in Bern, says, been DNA tested for PRA. “We “It’s thrilling to see advances in feline have never had any more PRA health understanding. I appreciate resulting in blind cats or kittens,” that these advances are a direct says Beth Bearry. “We are care- result of collaborations between ful to only breed carrier cats to research scientists like Dr. Kaelin non-carriers, and we test the litter and Dr. Lyons, cat enthusiasts like if we want to keep a cat in our me, funding organizations like breeding program.” Winn Feline Foundation, and pet The hope of being able to breed industry leaders like Purina.” n away from genetic diseases is the crux of the 99 Lives Initiative. “The long-term goal is to be able to use Purina appreciates the support precision medicine to treat cats of the Winn Feline Foundation, with diseases in which the gene and particularly Vicki L. Thayer, mutation is known,” Dr. Lyons says. DVM, DABVP (feline), former “With PRA, I would like to be at executive director and current the point where we could correct member of the board of direc- tors, in helping to identify this vision by putting a corrected version topic for the Cat Update. of the gene into the photoreceptor
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