Manchester Eye Tissue Repository Genome-Transcriptome Project

Dr Jamie Ellingford, University of Manchester - £249,950

This research will help our understanding of what gene changes, or combination of gene changes, are involved in macular dystrophies. Understanding the genes and the variants that are responsible for macular dystrophies is important, so that more patients can receive a correct diagnosis and to develop treatments for these genetic conditions.

What is the problem?

Many people with macular dystrophies don’t have a genetic diagnosis, instead they are diagnosed based on what changes are seen in the macula. Even after getting a genetic test, the result may be inconclusive because the changes in the gene may also be found in people without the condition.

This project aimed to better understand how genetic changes can affect or lead to macular dystrophies. Understanding the genes and the variants responsible for macular dystrophies is important for more patients to receive a correct diagnosis and for us to develop treatments for these genetic conditions.

What did the researchers do?

The researchers analysed a large repository of donated human eye tissue to assess how genes are expressed in different layers of the retina. Gene expression is the process by which the instructions in our DNA are converted into a functional product, such as a protein.

The researchers characterised over 200 individuals’ complete genetic codes, each made up of approximately 3.5 billion letters (DNA nucleotides) arranged in a specific sequence. They identified four to five million genetic variations (differences/changes in an individual’s genetic code compared to a reference sequence) for each person.

What did the researchers find?

The researchers identified common and rare genetic variations that were found to impact on gene expression and have been implicated in conditions such as age-related macular degeneration (AMD). Their comprehensive analysis expanded the spectrum and types of genetic variants known to have a critical role in controlling gene expression in the human retina. They were able to identify novel genes that increase susceptibility to AMD and found differences in how certain genetic variants affect the activity of genes already known to cause diseases.

What’s next?

Studies using the results from this project will continue to develop understanding of gene expression, as well as the role of genetic variation in the onset and presentation of macular dystrophies. This research could help us better understand how genetic diseases affect the retina and lead to new treatments. It could also help more patients receive a conclusive genetic diagnosis and be able to better manage and understand their condition.