PUNE: Focusing on complex diseases, biologists the world over have come together to find future healthcare solutions. Indian Institute of Science Education and Research (IISER), Pune is among the 20 centres the world over working on the Deep Genome Project.

Speaking to Sakal Times, Sanjeev Galande, one of the leaders of the Deep Genome Project, author of research editorial on the project and professor at IISER, Pune   said, “It is easier to find out the genetic disease and the care related to it as we can study the genes and make out what mutation has taken place and accordingly offer the therapy. However, when it comes to complex metabolic diseases, which include diabetes, cardiovascular diseases among others, there are multiple factors at play,” he said, adding these factors affect the person over the years. It does not take place in one day.

The research paper on the Deep Genome Project published in Genome Biology has been authored by 44 leading scientists, clinicians, and academics in 15 countries on 5 continents. It raises awareness of how limited our understanding is of function of most of our genes. 

“Genetic diseases are like hemophilia or sickle cells where we can recommend the cure. The world over, biologists, scientists and doctors are involved in research in mircobiota. They are checking whether microbiota affects Alzheimer’s or neurological diseases,” he said. 

“Only 3 to 5 per cent of our DNA code is used for making proteins. Researchers are beginning to learn what the other 95 per cent is for. But significant portions of the human genome, including much of the DNA, is still ‘dark’ and not understood. These ‘dark’ genes are understudied, so their functions and links to disease remain unknown. This lack of knowledge limits developments in medicine and prevents us from producing new drugs that target disease-linked proteins and finding new genetic markers that could assist in early diagnosis, even before symptoms start to show,” he added.

Mouse models are important for studying the human genome. We share 97 per cent of our DNA with mice and the mouse is a powerful tool for using gene editing techniques for analysing function of genes and their role in disease. 

The International Mouse Phenotyping Consortium (IMPC) is working to do this by turning off each gene and then studying the physical and chemical changes in a mouse. By 2021 over 9,000 mouse genes, around half the genome, will have been analysed and this has to be completed in order to fully understand the impact of genetics on disease. 

“This project was started in 2014,” said Galande, adding,  “Experts are working to catalogue all the genes in the mammalian genome, as well as their function and physical effects, to improve our understanding of disease and enable discovery of next generation therapies,” he said.

Experts propose four steps for the global mouse genetics research community to deliver a better understanding of the genome, and to continue to improve the resources that researchers and clinicians use for study of disease, efficient diagnosis, development of treatment and improved patient care.

Four steps for studying the mouse genetics

• The first step is to study the section of the mouse genome that produces proteins, which is 3 to 5 per cent of mouse DNA, describing which gene produces which protein and what happens when that protein stops working.  
• The second step is to target the noncoding section of the genome. This is the other 95 per cent of the mouse genome. DNA in the noncoding genome has important roles and can significantly affect how genes function. This will help understand how abnormalities in noncoding genome can contribute to disease.
• The third step is to turn the genetic information into clinical knowledge. Doctors, specialists, clinician-scientists, and researchers across the world will be able to use this information to study the role of genes in health and disease and find new targets for therapies.
• The fourth step is to ensure fast and easy access to this information so that it can be integrated in the clinical decision-making process. By streamlining the production of these mouse models, clinicians could diagnose patients more easily and administer targeted therapies with a better chance of being effective early in a patient’s course of disease.

Completing proj
The authors of research editorial state that completing this project will require continued funding and global collaboration. IMPC has been developing a functional catalogue of mouse genome, linking each gene to disease, enabling a better understanding of how genetic variation in the humans causes disease and identifying new targets for therapeutic intervention.