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Approved Research

Defining the Association of Human Endogenous Retroviruses (HERVs) and genes implicated in the inherited cardiac diseases

Principal Investigator: Professor Rameen Shakur
Approved Research ID: 93796
Approval date: April 19th 2023

Lay summary

Human Endogenous Retroviruses (HERVs)  are 'genomic scars' whereby viruses have integrated into the human genome throughout our evolution and our interaction with the environment we reside. This form of integration has been occurring into the human genome some 30-40 million years ago and now makes up 8% of the genome. Evidence suggests HERVs may cause a number of neurological and also autoimmune diseases,  such as rheumatoid arthritis and, among other rheumatic diseases. However, we are not so clear on the impact of such HERVs which are seen in different populations and are inherited across different subpopulations have on complex diseases such as cardiovascular diseases. To this end we are keen to understand in inherited heart muscle diseases called the Cardiomyopathies could the HERV signatures across patient groups explain why some patients develop disease outputs  from the underlying genetic changes in their genomes and others do not even though they may have inherited the same genetic changes. Furthermore, could such markers in ones genome be guide for early signs of disease developing? We have   identified potential candidate HERV regions  that are having gene expression effects in human diseases, namely in cardiac development and in the instigation of cardiac diseases. This has been achieved through a novel data pipeline we have developed and been able to curate and integrate global data on previously sequenced human normal and diseased patient hearts.  Given the variable penetrance in patient genotype and phenotype data in the inherited cardiomyopathies, this HERV map will enable us to understand why some phenotypes seem less clinical homogenous in populations where the genotype maybe prevalent. For example  the hypertrophic cardiomyopathies are prevalent in 1 in 200 of the population, but the incidence of clinical cardiomyopathy is not as high. The concept of a trigger or an initial environmental initiator remains, but this could be explained through the differing HERV backgrounds that are seen in individuals, which we know changes and degrades from generation to generation. This has not been undertaken before nor has this novel concept been applied previously in the chronic disease context nor in the complex diseases such as cardiovascular diseases before.