All of us begin our life as a single cell, roughly the width of a human hair. Within this cell is the human genome, made of 3 billion bases of DNA that carries the instructions for life. In 2001, after a decade of work involving scientists from over 16 countries, the sequence of the first human genome was completed at a cost of $3.8 billion.
Over the past decade, advances in DNA sequencing technologies have made it possible to sequence a human genome for $1,000 in a week’s time. A number of groups, using DNA sequencing, have begun to catalogue variations in human populations. This has enabled us to understand human migration and population history.
In 1865, Gregor Mendel discovered the two laws of inheritance that are now named after him. Almost 90 years later in 1953, the work of James Watson, Francis Crick, Maurice Wilkins and Rosalind Franklin, deciphered the structure of the molecule — DNA — that stores our hereditary information and gets transmitted from parents to children over generations.
What are the uses of genome sequencing?
Genomics is an interdisciplinary field of science focusing on the structure, function, evolution, mapping, and editing of genomes.
Advances in genomics have triggered a revolution in discovery-based research and systems biology to facilitate understanding of even the most complex biological systems such as the brain.
- Cancer is caused by deleterious mutations that accumulate in the genome. Inherited genetic disorders arise due to mutations in DNA that are passed on at birth. Increased risk for developing breast cancer is linked to variations in genes such as BRCA1 in the genome. Sequencing an individual’s genome or the tumour genome and comparing it to a reference human genome has helped identify the differences that contribute to the disease. In many cases, it has the potential to help with treatment decisions.
- In pregnant mothers, the blood also contains DNA from the fetus. Scientists have developed methods that can sequence the cell-free DNA in mother’s blood to monitor the genetic health of a developing baby.
- The genomics revolution has enabled sequencing a large number of organisms including bacteria, plants and animals.
- While it has confirmed the common evolutionary origin of life on earth, it has provided the code for a number of life forms.
- Sequencing of plants including cereals like rice and wheat has set the stage for rapid crop improvement.
- Understanding genomes of livestock such as cattle and goats has created a rich resource of genetic variations that can be used to produce animals with superior traits.
Perhaps this will also make interventional treatments feasible, in the not too distant future, thanks to the revolutionary advances brought about by the discovery of new gene-editing techniques, such as CRISPR/CAS9 (application of a precise genome editing/engineering technology). The editing combined with sequencing will enable rapid crop and livestock improvements that have the potential to end hunger and improve the standard of living across the world.
Examples of genome projects
- Human Genome Project (HGP)
The Human Genome Project (HGP) was an international scientific research project with the goal of determining the sequence of nucleotide base pairs that make up human DNA, and of identifying and mapping all of the genes of the human genome from both a physical and a functional standpoint. It remains the world’s largest collaborative biological project.
- Genome Project – Write
- 100K Genome Project
It aims to sequence the genomes of 100,000 infectious microorganisms to create a database of bacterial genome sequences for use in public health, outbreak detection, and bacterial pathogen detection. This will speed up the diagnosis of foodborne illnesses and shorten infectious disease outbreaks. The 100K Genome Project will provide a roadmap for developing tests to identify pathogens and trace their origins more quickly.
- 1000 Genomes Project
1000 Genomes project set out to map the genetic variations in human across the world sequenced 1,092 individuals from 14 populations. The resulting 20,000 GB bases of raw data will be basis for understanding of human genetic variations.
What implications do these developments have for India?
To gain fully from the genomics revolution, India needs to collect information about the genetics of its population and train manpower capable of interpreting it.
The information that is needed has to come from a large and sustained collection of data — fully sequenced individual genomes along with medical histories for the individuals who volunteer for this effort.
This kind of longitudinal study is what would allow actual physical manifestations relevant to health, e.g. specific illnesses, to be related to features in the genome.
China has been studying half a million people since their recruitment in 2004-2008. As India is much more genetically diverse — with something like 5,000 ethno-linguistic and religious groups (castes and others), all of which probably have some degree of genetic distinctiveness — it needs a larger survey.
The genetic distinctiveness of different Indian groups is in part the result of endogamy. While we cannot know the full impact of endogamy in advance of a proper survey, some recent research has shown that endogamy is very likely to be medically significant.
The genetic implication of this is that there are likely to be many recessive diseases stemming from single genes specific to individual groups that can be identified.
Decreasing disease burden
This knowledge could then also be quickly applied to the task of managing diseases in these groups as well as be used for genetic counselling that could reduce their incidence in future generations. As an example elsewhere, the founder group of Ashkenazi Jews have almost eliminated Tay-Sachs disease from their population by such means.
With large samples the technique of “genome-wide association studies” that compare genomes of cases and controls could be used to identify genetic risk factors related to common diseaseslike Heart diseases.
- This is a good point at which to note that such a survey of Indian genetic diversity will be an important asset, beyond disease genetics.
- The data collected as part of these efforts will also help to uncover the basic biological function of genes and their interactions, which are not yet fully understood.
- This knowledge will be useful to humanity worldwide and also offer India a chance to claim a piece of the global medical and scientific frontier.
As a large part of the enterprise would be theapplication of information technology or “bio-informatics”, the prospects of establishing viable commercial enterprises with synergies to existing IT champions are also promising.
What then is to be done?
There has been path-breaking work in using genomics to shed light on Indian history, a small number of hospitals are using genetic information to help patients.
- But all of this activity is on a much smaller scale than needed and is currently not generating the manpower required to equip the next generation of medical and research activities in the area.
- What is needed is a coherent push at the national level that involves government, academic institutions, the existing health-care industry, the IT industry and the nascent biotechnology industry.
- This coherent push should aim to set an ambitious but realistic objective of creating an Indian genetic data bank, to promote academic programmes that train scientists, technicians and doctors in this area and to create a regulatory framework that promotes broad objectives for both public and private sectors without being self-defeating.
Since both genetic data and biological samples are easily transported across borders, the Indian regulation cannot be shortsighted. It will simply cause Indian genomics to move abroad to places such as Singapore.
While this is eminently worthwhile as it will provide a broader pan-Asian set of data, it would be important to make similar investments at a national scale.
All in all, the time is ripe for India to begin its own genomics revolution. What is needed is a vision and leadership at the national level to leverage this and seize the day.