Mapping genetic susceptibility to hypertrophic cardiomyopathy in cats and assessing their utility as a disease study model

Lead Research Organisation: Royal Veterinary College
Department Name: Clinical Sciences and Services


Sarcomeric genes (e.g. MYBPC3) are commonly associated with hypertrophic cardiomyopathy (HCM) in humans and Maine coon and Ragdoll cats, but no such variants are identified in 40-60% of people with HCM. Clinical and histopathological similarities between the two species render cats a useful study model. Genome-wide genotyping technologies offer the opportunity for novel studies that could provide new insights in the genetic architecture of the disease in cats, potentially leading to previously unidentified causes in humans. Alternatively, if feline and human HCM mutations are similar, this would further support the notion of using cats as a model for the human disease.

In the proposed study we will conduct genome-wide association (GWA) analyses to detect loci affecting HCM susceptibility using 150 meticulously phenotyped domestic cats (HCM cases and breed-matched controls) from Birman, Norwegian Forest, British shorthair, Bengal and Ragdoll cats. Different GWA models will be investigated to assess the genetic architecture of HCM susceptibility within and across breeds. Analysis according to disease severity will help identify putative genetic modifiers. Using available pedigree and genomic relationships in a mixed model analysis we will estimate the heritability and the genetic effects associated with the identified significant SNP markers. In order to identify causative genes and mutations underlying HCM, whole-genome sequencing (WGS 30X coverage) will be performed in an affected family (heterozygous parents, and homozygous affected and non-affected offspring) and compared with published data in humans. Human WGS data from HCM patients and controls will be analysed focusing on human orthologue genes identified as good candidates in the cat analysis.

Blood and DNA samples are already available for this project. Phenotyping will be based on echocardiography and histopathology records at QMHA. Genotyping will be performed using a genome-wide 70K DNA array. The high-performance computer cluster at RVC will be utilised for all computational analyses.


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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M009513/1 01/10/2015 30/09/2023
1903448 Studentship BB/M009513/1 01/10/2017 30/09/2021 Jade Raffle