Unraveling the genetics of feline hypertrophic cardiomyopathy: A multiomics study of 138 cats

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease in cats, often leading to congestive heart failure, arterial thromboembolism, and sudden cardiac death. The genetics of feline HCM are poorly understood, and limited genetic discoveries remain breed or family-specific. We aimed to identify novel causative or disease-modifying variants in a large cohort of cats reflective of the general cat population. In a second cohort, we sought to characterize transcriptomic differences between HCM-affected cats and healthy controls. DNA was isolated from 138 domestic cats (109 HCM and 29 controls). No single or combination of variants of high, moderate, or modifying impact were identified in genome-wide analysis to cause or modify the disease severity of HCM. Several rare high and moderate-impact variants in genes associated with human HCM were detected in diseased cats. In a second cohort, left ventricular (LV), interventricular septal (IVS), and left atrial (LA) tissues..., WGS data generation
A total of 1-2 mL of whole blood were collected from the cephalic, saphenous, or jugular vein into EDTA blood collection tubes. DNA was either isolated from whole blood or from buffy coats after whole blood centrifugation at 2000 rpm for 15 minutes. Genomic DNA isolation was performed using commercially available kits (Gentra Puregene Blood kit, QIAGEN, Hilden Germany; ArchivePure;5Prime) and by following the respective manufacturer’s protocol. High-quality unfragmented DNA was selected by a combination of 1% agarose gel visualization and spectrophotometric confirmation (a 260/280 ratio of ~1.8 and a concentration of > 50 ng/uL; NanoDrop One/One, Thermofisher, Waltham, GA, USA). Samples were stored at -20°C until ready for shipment to Theragen Bio Co., Ltd, Gyeonggi-do, Republic of Korea for WGS. Paired-end DNA libraries were generated with a TruSeq DNA Nano library prep kit. Samples were then pooled and sequenced at ~30x coverage on the Illumina NovaSeq6000 platf..., # Unraveling the genetics of feline hypertrophic cardiomyopathy: A multiomics study of 138 cats

Dataset DOI: [10.5061/dryad.cjsxksnjh](10.5061/dryad.cjsxksnjh)

## Description of the data and file structure

### Data available

1\. A population level vcf of polymorphic SNP and indel variants were called among 138 domestic cats with and without hypertrophic cardiomyopathy (HCM). The VCF was generated by mapping paired wgs fastq reads to the Fca126 reference genome with bwa mem and calling variants through GATK4 best practices. Variant annotations were generated with Ensembl's VEP based on Fca126 gene and exon boundaries.  The vcf file contains meta-information lines, followed by a header line specifying fixed fields per sample and subsequent data lines detail variants at genomic positions. The fixed fields include chromosome (CHROM), position (POS), identifier (ID), the reference base(s) (REF), alternate base(s) (ALT), quality (QUAL), filter status (FILTER), and additional information ...,