Is arthritis due to DNA’s dark matter?

Much of the universe is thought to be made up of invisible ‘dark matter’; in the same way, much of the genome consists of DNA that does not code for a protein and was thought to be unimportant. However, this ‘genomic dark matter’ may be important in controlling gene function in health and disease, and it is these interactions that Steven Witte is exploring [Image Credit: ESA/Hubble]

By Steven Witte

Many autoimmune diseases – from arthritis to ulcerative colitis – have a strong genetic component, being passed down from father to son and mother to daughter. Yet the genetic secrets of how they work are still very much a mystery.

It is this mystery that brought me from America to the UK and made me take time out of my medical studies at the University of Alabama School of Medicine to work at the Sanger Institute. Over the next four years I will be investigating how the genome regulates itself in mice to try to understand what is happening in the genomes of people with allergies and autoimmune disorders.

In high school I became entranced by the complex simplicity of genetics. That such a basic material as DNA is able to carry all the information needed to make every cell of our bodies – and make them work together in harmony – really caught my imagination. The idea that scientific research might be able to understand and ultimately treat human disease inspired me to become a doctor.

It was during my medial studies that I became hooked on understanding immune diseases. I was fascinated by how such a wide range of problems, which produce a huge diversity of symptoms, can be caused by problems with our own DNA. But more importantly I was disappointed that we have no idea how to fix these problems, because we don’t know what is causing them.

Since we now have a comprehensive map of all the genes in the human body and we know that genetics lies at the heart of these diseases, it seemed reasonable to assume that the answers must be tantalizingly close. However, the genome is proving to contain many more secrets than we first thought.

Much like our understanding of the universe, genomic research is finding that ‘the more we know, the more we find we have yet to discover’. Recently published research by the ENCODE and GENCODE projects have hinted that our genomes contain a wide expanse of ‘dark matter’ whose role and workings we haven’t yet unlocked.

Once thought to be ‘junk’ it now seems that this expanse of DNA – known as non-coding DNA because it does not produce protein – has the potential to answer questions that have puzzled medical researchers for decades.

I believe that genomic dark matter could contain the answers to our questions about the causes and workings of immune diseases, including arthritis. To find out more I will be working with mice to discover whether or not non-coding RNA sequences contribute to these diseases. These non-coding RNA sequences are found in the genome’s dark matter and appear to control the actions of other genes by switching them on or off.

If we can understand the control mechanisms that affect how genes work – and what happens when they go wrong – we hope to be able, ultimately, to develop ways to fix them. I’m passionate to help find these answers, so that we can help people with debilitating diseases.

Steven Witte is a first year PhD student from the NIH Oxford Cambridge Scholars Program,  studying non-coding RNA in the immune system. He is a part of the Mouse genomics group led by Professor Allan Bradley at the Wellcome Trust Sanger Institute.

Related Links

• Mouse genomics group
• Professor Allan Bradley