Epigenetic modifications associated with development of cardiomyopathy

Functional transcription is essential for proper cell function.

Erroneous transcription, due to mutations in promoters/enhancers or epigenetic modifications of the DNA, can lead to disease.

Epigenetic modifications are reversible changes targeting the genomic structure that alter gene expression without affecting the DNA sequence.

These changes are suggested to explain some of the observed incomplete penetrance of cardiomyopathy (CM), but fresh human tissue to study this is seldom available.

Formalin-fixed paraffin-embedded (FFPE) tissues are valuable due to their abundance and well characterized pathology, but limited in use of whole genome sequencing (WGS) due to DNA-degradation.

However, with important biomarkers of disease identified in fresh tissue, screening for relevant targets in valuable FFPE-samples will be possible and result in major improvement of their use.The aim is to study the epigenomic impact on CM in hearts of animals and humans.

This will be done by WGS and transcriptome sequencing of fresh and FFPE-samples from healthy and CM-affected cats and dogs, but also human FFPE-tissue.

This way epigenetic modifications of the genome and transcriptomic variation, such as nucleotide methylation and/or histone modifications, but also changes in gene expression can be studied.

We believe this project provide valuable knowledge regarding an improved understanding for the development of such a fatal group of diseases as CM, but also suggest new targets for treatment.