The battle has long raged over the impact of nature (in the form of genetics) vs Nurture (in the form of environmental factors) on an individual’s susceptibility to disease. Clearly both play a huge part in deciding the expressed phenotype, but scientists always struggled to explain the variation in phenotype found between identical genomes even in the same lab conditions or between twins raised in the same household.
The reason for these variations may well be due to the unknown purpose of large sections of DNA previously believed to be ‘Junk’ (also known as Dark Matter). New research shows that 80% of the genome is now biologically relevant as opposed to the 2% of protein coding genes that were previously the regions focussed on.
These findings were identified by the Encode project (The Encyclopaedia of DNA Elements), which recently published 30 connected open access journal papers based on the work of 400 scientists from 32 labs in the UK, US, Spain, Singapore and Japan. Started 5 years ago the project has cost $288 million and was set up to explain the findings of the 2003 Human Genome Project, which highlighted only 2% of genes were involved in producing blood, bone and tissues. The work was based on more than 1600 experiments and 180 different cell types.
The project identified four million gene ‘switches’ or regulatory genes, which are areas of DNA that control when genes are turned on and off in a cell and hence how much of any particular protein is produced. It was of particular interest that these switches were often not located close to the gene encoding regions of DNA, explaining the assumption that these other regions were Junk. This had been questioned for some time has and now been proved incorrect.
It seems regulatory genes are of significance for rare diseases, such as Crohn’s disease, as well as more common diseases such as cancer. Considerable early excitement surrounded mistakes in single gene or monogenic disease such as sicklecell anaemia, but the complexity of human biology has proved that the majority of disease is polygenic. The impact of mistakes in regulatory genes is much more significant and is suspected to be 5-10 times more impactful than mistakes in coding genes. For example, cancer defects in 20 regulatory genes surface repeatedly in 17 major cancer types, providing new avenues for drug targets and personalized treatments.
Use of these new findings in medical treatment is still a long way off. This project demonstrates why basic, fundamental research is key to understanding the building blocks of life. As we continue our journey into the mysteries of human existence and disease susceptibility, the incredible foundation of our lives that is DNA continues to amaze us with its sophistication and complexity.