Tag Archives: genetics

As new age technology, such as high-throughput sequencing and nanopores, slashes both costs and time needed for genomic analysis, the age where commercialisation of individual one thousand pound gemones dawns. With its inevitable manifestation around the corner, it has never been more pressing to assess impacts, both social and clinical, so that we can truly be prepared for the changes in how the genetic world interacts with everyday life.

As 10,000 new germline mutations are identified annually, and 300 new inherited disease genes highlighted, personalised genomic sequencing could be used to locate, monitor and understand further disease-associated mutations, though this will only be possible if the data is in fact made public. Inheritance of disease will be better understood, which is a very exciting prospect for potential parents, as current prenatal tests only identify a fraction of potential defects. Currently personalised genome sequencing is used for prenatal and preimplantation genetic testing of conditions such as Turner’s syndrome and muscular dystrophy; however these tests are currently available only to high risk children. With the potential commercialisation of sequencing, testing may be readily available to everyone, undeniably changing the way in which these tests are implemented and as with most change, the line between it being positive and negative lies thin.

‘All creatures would agree that it was better to be healthy than sick… well fitted than ill fitted for their part in life; in short that it was better to be a good rather than a bad specimen of their kind’ – Galton

Global screening of embryos for disorders could lead to self directed human evolution, in other words, eugenics. The risk of profitable ‘designer babies’ could lead personal genomics to encounter ethical scrutiny, therefore a balance will have to be struck:

‘Given the power and the authority granted to parents to seek to improve or better their children… at least (by) some forms of genetic selection or alteration (it) seems equally ethically defensible if they are undertaken freely and do not disempower or disadvantage their children’ – Galton

Certain countries have banned inappropriate preimplantation diagnosis, such as that for sex selection in the UK.

After heart disease, cancer and stroke, adverse drug reaction is the fourth most common cause of death for americans, the fast growing field of pharmacogenetics will find genomic profiles vital in the production of personalised medication. Not only would personalised medication reduce deaths from undesirable reaction, but these tailor made gems would benefit both diagnosis as well as treatment efficiency. While focusing on disease, it must be said that it’s susceptibility is complex, often involving multiple genes, with a partial influence of environmental exposure to certain substances, such as carcinogens. Shedding light on perhaps a limitation of sequencing is the reality that it is not likely to have a great deal of predictive power; a study analysing over 53,000 pairs of monozygotic twins for the incidence of 24 diseases, ranging from autoimmune to obesity associated diseases and cancer, implied 2% of women undergoing whole genome sequencing would have mutations linked to ovarian cancer detected; at least a one in ten chance of developing ovarian cancer. However, the remaining 98% having found no mutations would still be at a 1.4% risk, that of the general public; it would be fair to say that the day when sequences produces infallible figures is a while away.

Unfortunately sequencing may also reveal to patients more than they were prepared to know, diagnosing age-onset, incurable diseases such as Alzheimer’s disease. And once the diagnosis has been confirmed, who else has the right to know? New guidelines issued by the UK GMC allow disclosure of patient information, given the diagnosis of a genetically heritable disease to family members if it is ‘justified in the public interest’. Genetic availability dawns a problematic issue as the UK lacks a counterpart to the USA Genetic Information Nondiscrimination Act.

There also remains the risk of people missing out on potentially life-saving intervention; as genomic sequencing enable quick, cost-efficient diagnosis and family history has long been collected as a means of assessing risk, individuals may not get tested in the fear of employment and insurance discrimination. Although comfort can be taken in the fact that the US Department of Energy and the National Institute of Health devotes 3-5% of their annual Human Genome Project budget towards studying the ethical, legal and social issues surrounding genetic availability, illustrating how research into the issue is currently active.

Sequencing potentials are astounding; from revolutionising diagnosis of disease to screening embryos for chromosomal abnormalities. Personal genomic sequencing allows useful deviations from the reference genome to be analysed. In turn, these incentivise an increase in the sophistication of modern technology. The ethical issues of pharmacogenetics, eugenics and social discrimination dawn as a result of personal genomic sequencing; although there is evidence that research is going towards investigating problematic issues, with rules and regulations already in place. As time progresses, so will our knowledge, all that remains is the hope that we are prepared for the double helix’s dormant revelations.

Image reproduced from pharmaceuticalshealthcare.blogspot.com

We truly are living in the age of technology, but not as we know it. Machines will no longer be developed through scientific knowledge; scientific knowledge will be developed through machines.

Dr Eugene Schuster
Functional Genomics of Aging
Genetics, Evolution and Environment
University College London

Science Writer Sumaya Anwar interviews Dr Eugene Schuster to find out more about the Archon Genomics X prize. The $10 million prize competition, which awaits a team capable of sequencing 100 genomes, at a cost of $1000 per genome, in 30 days or less with no more than 1 error in 1,000,000 bases!

It seems surprising to see head-to-head competition in the scientific world, is this something you have come across often or is the vision of scientists working fully together and sharing their findings more realistic?

There is a growing movement in the scientific community for this type of competition – another example is https://www.innocentive.com and shows that the crowdsourcing movement has entered into the scientific community. I think the impact of these types of competitions will be limited and focused to very particular research areas and will not greatly expand as a funding source for academic research. This is because research is very expensive to conduct and you need funding from the beginning. Only an extremely well funded lab or company could undertake such a project and most likely would already have funding in place to do this type of research – so winning the X prize would only be a bonus. However, I think it is much more likely that crowdfunding – when someone proposes to build or do something and ask the public for funds to accomplish the task – will become a bigger part of scientific funding in the future.

The 100 genomes to be sequenced have been donated from centenarians; as a researcher within the aging field how would this genomic database benefit you?

Although, my group studies ageing in a tiny worm called Caenorhabditis elegans, we are interested in identifying evolutionarily conserved mechanisms that can affect lifespans. We would clearly benefit by this research because when human genes are discovered that might help humans to live past 100 we can immediately test if the equivalent genes in worms also affect lifespan. For example, we study a gene called daf-16 in worms and almost 20 years ago the scientist Cynthia Kenyon discovered that this gene plays an important role in extending the lifespan of worms. In the past few years the equivalent gene in humans (called FOXO3A) has been implicated in helping humans to live past 100. We believe that by understanding the role of this gene in worms we can start to understand what it does in humans.

Which standard of the competition do you think is going to be most difficult to meet: 98% completeness of the sequences, the time restriction of 30 days or less, the cost restriction of $1,000 per genome or achieving complete haplotype phasing of the chromosomes?

Complete haplotype phasing will be the most difficult to achieve. It is very difficult to predict inheritance without sequencing the parents or related individuals. To do this probably requires the ability to sequence very long stretches of single strands of DNA with very little error – which is probably beyond current methods.

The process of aging is no doubt complex; research tends to be conducted on model organisms, would the development of genomic sequencing technology mean the end of model organism use?

No because having genomic information does not mean the end of experiments. Large sequencing studies in human will only provide weak evidence that a gene may be involved in a disease or the prevention of a disease. Experiments will have to be done to show a definitive link between the disease and the gene and it is much easier to test these links in model organisms. In worms, you can do an aging experiment in a few weeks. If I started a study in humans, it is likely that the study would out live me.

Steve Jobs had his genome sequenced for $100,000; $1,000 seems much more commercially viable for the general public. What does the current price stand at?

To get a high quality genome with very few errors it would cost about $10,000 today. Once the price gets near $1000 (approximately the cost of an MRI scan) then it can become reasonable for insurance companies or the NHS to sequence a genome if there is good reason to suspect that there is a genetic basis for a disease or symptom. However, this does not include the cost of making sense of that genome and including analysis and interpretation costs may significantly add to the price.

Which technologies are currently at the forefront in terms of cost-efficient sequencing and how do they achieve this?

Two companies that have recently announced low cost genome sequencing are Ion Torrent and Oxford Nanopore Technologies. Both companies will use a semiconductor based technology – Ion Torrent bases the technology on detecting ion charges during the sequencing process and Oxford Nanopore detects changes to the electrical current as a strand of DNA is passed through a nanopore. The major cost savings of these technologies is that they do not rely on optics (i.e. expensive lasers and scanners) nor on labelled samples (older technology typically relies on costly fluorescent labels to detect sequence).

This competition was first proposed in October 2006, what date would you estimate the commercialisation of the $1000 genome?

I would estimate that it will take 2 years before the first commercial $1000 genome (including the cost of interpretation) is available.