Crowdfunded whole-genome sequencing of the celebrity cat Lil BUB identifies causal mutations for her osteopetrosis and polydactyly

Abstract

Rare diseases and their underlying molecular causes are often poorly studied, posing challenges for patient diagnosis and prognosis. The development of nextgeneration sequencing and its decreasing costs promises to alleviate such issues by supplying personal genomic information at a moderate price. Here, we used crowdfunding as an alternative funding source to sequence the genome of Lil BUB, a celebrity cat affected by rare disease phenotypes characterized by supernumerary digits, osteopetrosis and dwarfism, all phenotypic traits that also occur in human patients. We discovered that 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. We communicated the progress of this project to a large online audience, detailing the 'inner workings' of personalized whole genome sequencing with the aim of improving genetic literacy. Our results highlight the importance of genomic analysis in the identification of disease-causing mutations and support crowdfunding as a means to fund low-budget projects and as a platform for scientific communication.

Negotiating Disability in Celebrity Cat Lil BUB’s Eating Videos

“…Certainly, Bridavsky did not hide BUB's disabilities, but rather put them on display as an example of perseverance and positivity. In fact, Bridavsky even assisted scientists who wanted to sequence BUB's genome in order to study her unique mutations (Bridavsky et al 2019), further accentuating BUB as a spectacle who, to add to Elaine Laforteza's analysis (2014), can be stared at so intimately that even her genetic data is no private matter. Nevertheless, it is also crucial to note that Bridavsky exhibited transparencyalbeit curated-in the practice of caring for a disabled animal companion and he actively challenged the cultural understanding of disability as something so abysmal that even death would be a more desirable option.36 Sequencing BUB's 34…”