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At ASHG, 99 Cat Genomes Project Presenter Points to Feline Potential as Trait, Disease Model

BALTIMORE (GenomeWeb) – At the American Society of Human Genetics annual meeting here yesterday, a representative from the 99 Lives Cat Whole Genome Sequencing Initiative discussed progress being made to sequence 99 or more cats from diverse breeds and locations to understand cat conditions and to model human disease and traits.

The University of Missouri at Columbia's Leslie Lyons said members of the team have already sequenced and started analyzing the genomes of 54 cats, including representatives from two wild cat species and 50 domestic cats. The set includes three successfully sequenced cat trios, each featuring parents and offspring with distinctive physical traits.

"Analyses of trios, duos, and singleton cases have all led to variant discoveries for cat models of human disease," she and her co-authors noted in the abstract for Thursday's presentation.

The ongoing sequencing effort stems from the notion that the tens of millions of cats found in American households — together with their domestic and feral counterparts elsewhere — could hold clues to maladies that afflict both cats and humans.

By sequencing and comparing the genomes of many cats from genetically distinct cat "ethnic groups," Lyons explained, the team hopes to define normal genetic variation within cats and uncover genetic variants with ties to particular traits or conditions.

There is also interest in using such data to boost wild cat conservation strategies and come up with improved treatments for ailing pets.

The first draft of the cat reference genome, generated using DNA from an Abyssinian cat named Cinnamon, was originally published in Genome Research in 2007 by a team led by National Cancer Institute investigators.

In 2014, a higher-quality version of the cat genome appeared in the Proceedings of the National Academy of Sciences by a Washington University-, Texas A&M University-, and University of Missouri-led team as part of a broader comparative genomics study on domestic cat biology, traits, and behavior.

Although housecats don't typically get as broad a range of spontaneous cancers as domestic dogs, at least two types of lymphoma are common in cats, as is kidney failure, Lyons noted. Cats are also susceptible to infectious disease and common diseases such as diabetes, allergies, and asthma, she explained.

The large potential pedigrees, population structure, and linkage patterns being parsed from cat genomes make the animals amenable to further study as well, according to Lyons. She noted that there appear to be roughly a dozen cat "ethnicities" for feral and domestic cats from different parts of the world with between 20 and 25 genetically distinct breeds.

For the 99 Lives genome sequencing project, the team is systematically producing two PCR-free libraries per cat, which are sequenced to between 15-fold and 30-fold average genome coverage using Illumina HiSeq paired-end sequencing.

The resulting reads are being aligned to the cat reference genome with the help of data analysis and visualization tools from Maverix Biomics, which is partnering with the researchers on the study.

Using such data, members of the team have tracked down mutations associated with polycystic kidney disease in Palas cats. The kidney condition is common in Persian and other exotic breeds, Lyons said, suggesting cats might make a suitable model for some human kidney conditions.

Likewise, the work has uncovered alterations in genes such as AIPL1 and IQCB1 that appear to be involved in a progressive blindness condition in cats known as progressive retinal atrophy. And variants that appear to play a causal role in feline lymphomas are currently being validated and confirmed, Lyons noted.

The team is continuing to look into these and other conditions in cats such as bone disorders, dwarfism, and heart conditions.

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