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A fundamental hurdle hampering the interpretation of feline disease variant data is the availability of a high-quality, gapless reference genome. The previous domestic cat reference, Felis_catus_8.0, contains over 300,000 gaps, compromising its utility for identifying all types of sequence variation [ 16], in particular SVs. In conjunction with various mapping technologies, such as optical resolved physical maps, recent advances in the use of long-read sequencing and assembly technology has produced a more complete genome representation (i.e., fewer gaps) for many species [ 17– 20]. Choi JW, Chung WH, Lee KT, Cho ES, Lee SW, Choi BH, et al. Whole-genome resequencing analyses of five pig breeds, including Korean wild and native, and three European origin breeds. DNA Res. 2015;22(4):259–67. Epub 2015/06/29. pmid:26117497; PubMed Central PMCID: PMC4535618. However, the introduction of the domestic cat to the Americas from Europe and Africa accompanied by T. gondii strains adapted to the domestic cat provided conditions for the emergence for the first time of toxoplasmosis as a major zoonotic disease in those areas,” he said. The 1000 Genomes Project Consortium, Auton A, Brooks LD, Durbin RM, Garrison EP, Kang HM, et al. A global reference for human genetic variation. Nature. 2015;526(7571):68–74. Epub 2015/10/04. pmid:26432245; PubMed Central PMCID: PMC4750478. Data Availability: The datasets supporting the conclusions of this article are available in NCBI’s sequence read archive. The whole genome sequence data generated in this study have been submitted to the NCBI BioProject database ( http://www.ncbi.nlm.nih.gov/bioproject/) under accession number PRJNA16726. Illumina WGS data used in this study can be found under the NCBI BioProject accession PRJNA308208. Source code used for analyses is publically available on GitHub ( https://github.com/mu-feline-genome/Felis_catus_9.0_analysis).

Foldynova-Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Hum Mutat. 2012;33(1):29–41. Epub 2011/11/03. pmid:22045636; PubMed Central PMCID: PMC3240715. Rausch T, Zichner T, Schlattl A, Stutz AM, Benes V, Korbel JO. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics. 2012;28(18):i333–i9. pmid:22962449; PubMed Central PMCID: PMC3436805. Fabrizio F, Calam AE, Dobson JM, Middleton SA, Murphy S, Taylor SS, et al. Feline mediastinal lymphoma: a retrospective study of signalment, retroviral status, response to chemotherapy and prognostic indicators. J Feline Med Surg. 2014;16(8):637–44. Epub 2013/12/25. pmid:24366846.Macavity: The Mystery Cat" – Bombalurina, Macavity, Mungojerrie, Rumpleteazer, Griddlebone & Company Hug P, Kern P, Jagannathan V, Leeb T. A TAC3 Missense Variant in a Domestic Shorthair Cat with Testicular Hypoplasia and Persistent Primary Dentition. Genes. 2019;10(10):806. Another hurdle for performing feline genomic medicine is the availability of WGS data from various breeds of cat with sufficient sequencing depth to uncover rare alleles and complex structural variants. Knowledge of variant frequency and uniqueness among domestic cats is very limited and is crucial in the identification of causal alleles. As a result of the paucity of sequence variant data across breeds, the 99 Lives Cat Genome Sequencing Initiative was founded as a centralized resource with genome sequences produced of similar quality and techniques. The resource supports researchers with variant discovery for evolutionary studies and identifying the genetic origin of inherited diseases and can assist in the development of high-density DNA arrays for complex disease studies in domestic cats [ 1, 21– 24].

Yang J, Li WR, Lv FH, He SG, Tian SL, Peng WF, et al. Whole-Genome Sequencing of Native Sheep Provides Insights into Rapid Adaptations to Extreme Environments. Mol Biol Evol. 2016;33(10):2576–92. Epub 2016/07/13. pmid:27401233; PubMed Central PMCID: PMC5026255.Chang, Justin (18 December 2019). "Review: 'Cats' is a horror — and an occasional hoot". Los Angeles Times. Archived from the original on 19 December 2019 . Retrieved 19 December 2019. There will be regular updates for "The Battle Cats" with new and improved features. However, some older devices may not be able to support these changes. Online Mendelian Inheritance in Animals (OMIA). Sydney School of Veterinary Science, 03/12/2019. World Wide Web URL: http://omia.org/. Available from: http://omia.org/. Andrew Lloyd Webber warned Universal bosses Cats movie would be 'a car crash' ". Film-News.co.uk. 9 June 2021.

An important concern with using human constraint metrics for identifying causative variants in cats is the potential for false positives. For example, out of 16 SNVs initially identified as potential feline disease candidates, many belonged to cats with no recorded disease status ( S7 Table). However, since a large fraction of healthy humans also carried SNVs matching similar disease causing criteria as used in cats [ 58], evolutionary distance between humans and cats is unlikely to be a significant contributing factor to false positive candidate disease variant identification. Instead, the frequency of high impact variants in constrained genes is likely due to the limited resolution provided by analyses at the gene level. Recent strategies in humans have confronted this problem by focusing on constraint at the level of gene region. These analyses identified many genes with low pLI values that contained highly constrained gene regions that were also enriched for disease causing variants [ 71]. Alternatively, another strategy for further refining constrained regions could involve combining genomic variation from multiple species. Many variants observed in cats, along with their impact on genes, are likely unique to cats and could potentially be applied to variant prioritization workflows in humans. D'Alessandro, Anthony (25 September 2018). " 'Cats' Cast Grows: Tom Hooper-Directed Musical Adds Laurie Davidson". Archived from the original on 26 September 2018 . Retrieved 25 September 2018.D'Alessandro, Anthony (19 November 2018). "Rebel Wilson To Play Jennyanydots In Universal-Working Title's 'Cats' ". Archived from the original on 19 November 2018 . Retrieved 19 November 2018. Funding: Funding for this project has been provided in part by Nestlé Purina to pay for personnel salaries and sequencing (W.C.W. and R.M.), Wisdom Health unit of Mars Veterinary to pay for personnel salaries (L.A.L.), Zoetis to pay for RNA sequencing used in annotation (L.A.L), the University of Missouri College of Veterinary Medicine Gilbreath-McLorn endowment was used for the BioNano optical map (L.A.L.), and Winn Feline Foundation W15-008 (W.J.M.), Winn Feline Foundation/Miller Trust MT14-009 (W.J.M.) ( https://www.winnfelinefoundation.org/), and Morris Animal Foundation D16FE-011 (W.J.M.) ( https://www.morrisanimalfoundation.org/) were all used for PacBio sequencing. The funders had no role in study design, data collection, data analysis, interpretation of results, or decision to publish.