Now nearly five years later, with the help of a successful crowdfunding campaign, an international feline genome consortium, and Lil Bub’s “dude,” Mike Bridavsky, they finally have. In her internet-royal blood the scientists uncovered two genetic abnormalities that help explain her signature squee-ness—extra toes, short stature, wonky gait, and a tongue that is forever lolling out of her mouth. Their discovery, which they posted on the preprint server bioRxiv in February, is not only helping Bridavsky care for Lil Bub as she ages, it could one day aid doctors in better treating human patients of osteopetrosis. And just as Bub blazed a trail for viral cat celebrity, by having her DNA sequenced she is once again leading the way, only this time toward precision veterinary medicine.
In some respects, Lupianez and his partners in this project, fellow Berlin resident Daniel Ibrahim and University of Pennsylvania’s Orsolya Symmons, now know Lil Bub more intimately than pretty much anyone. They spent four years crowdfunding money to sequence the cat’s genome, creating whimsical videos and a blog to demystify a complicated process, and analyzing Bub’s genetic material to discover what makes her so very unusual.
BUB's fastq files and how to read them.
how to spot variations in a genome that you just sequenced.
4 of 4: how to filter all of the variation in LilBUB's genome for the bits that are relevant
Lupianez and Ibrahim, for their part, wondered whether the cat’s two already-diagnosed conditions — polydactyly, the term for her extra digits, and the rare bone-hardening disorder osteopetrosis — might be the result of one gene mutation, which would be an important finding.
Instead, they found in an initial test that Lil Bub’s polydactyly resulted from the same gene mutation that causes it in Ernest Hemingway’s famous six-toed cats, generations of which have lived at the writer’s former home in Key West, Fla.
That mutation is different from those that cause polydactyly in cats outside North America, which means Bub is somehow related to the Hemingway cats.
1 of 5: what is genome sequencing?
2 of 5: Sequencing LilBub's Magical Genome
3 of 5: How to make a LilBUBome - Part 2
4 of 5: how to spot variations in a genome that you just sequenced
5 of 5: how to filter all of the variations in LilBUB's genome
What it all adds up to, the researchers said, is a new case study for an extremely rare disorder — another example of how it can manifest itself and progress. Which means that Lil Bub, viral Internet cat, could help doctors better treat human patients whose osteopetrosis stems from the same gene mutation. The complete data set is available in the open-access journal bioRxiv, in the hope other scientists might make other Lil Bub-related discoveries, such as the cat’s breeds.
The Find: Lil Bub is affected by two distinct mutations: a heterozygous mutation in the limb enhancer of the Sonic hedgehog gene, previously associated with polydactyly in Hemingway cats; and a novel homozygous frameshift deletion affecting the TNFRSF11A (RANK) gene, which has been linked to osteopetrosis in humans.