Chromosome-scale assembly with improved annotation provides insights into breed-wide genomic structure and diversity in domestic cats

Abstract

Introduction

Comprehensive genomic resources offer insights into biological features, including traits/disease-related genetic loci. The current reference genome assembly for the domestic cat (Felis catus), Felis_Catus_9.0 (felCat9), derived from sequences of the Abyssinian cat, may inadequately represent the general cat population, limiting the extent of deducible genetic variations.

Objectives

The goal was to develop Anicom American Shorthair 1.0 (AnAms1.0), a reference-grade chromosome-scale cat genome assembly.

Methods

In contrast to prior assemblies relying on Abyssinian cat sequences, AnAms1.0 was constructed from the sequences of the phylogenetically distant and more popular American Shorthair breed, which is related to more breeds than the Abyssinian cat. By combining advanced genomics technologies, including PacBio long-read sequencing and Hi-C- and optical mapping data-based sequence scaffolding, we compared AnAms1.0 to existing Felidae genome assemblies (20 scaffolds, scaffolds N50 > 150 Mbp). Homology-based and ab initio gene annotation through Iso-Seq and RNA-seq was used to identify new coding genes and structural variations.

Results

AnAms1.0 demonstrated superior contiguity and accuracy than existing Felidae genome assemblies. Using AnAms1.0, we identified over 1.5 thousand structural variations and 29 million repetitions compared to felCat9. Additionally, we identified > 1,800 novel protein-coding genes and structural variants. Notably, olfactory receptor structural variants and cardiomyopathy-related variants were identified.

Conclusion

AnAms1.0 facilitates the discovery of novel genes related to normal and disease phenotypes in domestic cats. The analyzed data are publicly accessible on Cats-I (https://cat.annotation.jp/), which we established as a platform for accumulating and sharing genomic resources to discover novel genetic traits and advance veterinary medicine.