Dr Anna Middleton is an Ethics Researcher and Registered Genetic Counsellor, based at the Wellcome Trust Sanger Institute. She leads the ethics component of the Deciphering Developmental Disorders study, a collaborative project involving WTSI and the 23 National Health Service Regional Clinical Genetics Services in the UK. This project involves searching for the genetic cause of developmental disorders, using array-CGH, SNP genotyping and exome sequencing, in ~12,000 children in the UK who currently have no genetic diagnosis.
One of the issues raised by this, and many other research projects, is what should happen to ‘incidental’ findings, i.e. potentially interesting results from genomic analyses that are not directly related to the condition under study. Here Anna discusses the research she is conducting on this topic as part of the DDD study, and provides a link to the DDD Genomethics survey where you can share your own views (I should also disclose here that both Caroline and I also work on the DDD study).[KIM]
Whole genome studies have the ability to produce enormous volumes of valuable data for individuals who take part in research. However, as a consequence of analysing all 20,000+ genes, whole genome studies unavoidably involve the discovery of health related information that may have actual clinical significance for the research participant. Some of this will be considered a ‘pertinent finding’, i.e. directly related to the phenotype under study (e.g. the child’s developmental disorder); some of this will be considered an ‘incidental or secondary finding’ in that it is not directly linked to the phenotype under study or the research question that the genomic researchers are trying to answer.
Continue reading ‘Ethics and Genomic Research: ‘Genomethics’’
I have no strong family history of any disease, despite having 7 blood aunts and uncles and countless cousins. So when I sent my spit off to 23andMe at the start of the Genomes Unzipped project, I was expecting something very similar to Caroline’s experience: a 5% increase in risk here, a 2% decrease in risk there, nothing that would really tell my anything about my health.
However, this was not my experience. Along with a pretty interesting Y haplogroup, I also had three unexpected and potentially worrying health results. I am a cystic fibrosis carrier, a hemochromatosis compound heterozygote, and have a strongly elevated risk of age-related macular degeneration. This cocktail of genetic disease certainly was not what I came to the test expecting!
After some thinking, I decided to take my test results to my GP, and see if there was any advice or testing he would recommend. In the end, my GP referred me to a clinical geneticist, which started a cascade of appointments which in turn led to a number of important changes in how I treat my own health.
What was most interesting is how the whole experience got me thinking about my health as something I am in charge of. I have since made a number of important life-style changes, some of them directly related to my genotyping results, some more generally to improve my overall health.
The point of this post is just to go through some of the experiences, what I have learned about specific conditions, and what changes I have made to my life since. In some sense, I feel like my experience is a case-study in what good outcomes can come from personal genomics, both for specific conditions, and more generally for how genetic data can change your own approach to your health.
Continue reading ‘A case study in personal genomics’
To celebrate 10 years since the back-to-back publications of complete human genomes in Science and Nature, Science has published series of articles looking back at the last 10 years of genomics, and forward to the future. The article contains short essays from Francis Collins and Craig Venter, the former talking about some of the successes of medical sequencing (including giving a name and photograph to the exome-sequenced IBD patient I discussed a few weeks ago), and the latter discussing how far we still have to go before genomics can reach its potential. Baylor’s Richard Gibbs talks about how the large-scale technical discipline of genomics and the biological subject of genetics are starting to re-merge, after the Human Genome Project saw the two diverging, and there is an oddly inspiring comment from theologian Ronald Cole-Turning about how genomics is redefining our vision of humanity.
Of particular interest is an article by Eliot Marshall on why genomics hasn’t yet had a large effect on medical practice, and what needs to be done to allow the genomic revolution to trickle into medical care. He argues that scientists and doctors need to meet each other half way; scientists need to focus more on showing the direct clinical utility of genomics, whereas doctors need to be more ready to accept new technologies and discoveries, and adapt the way they practice medicine to make full use of them. [LJ]
Continue reading ‘A decade of genomics, 60 new genomes, parenthood and sharing genetic data, and more on data return’
Illumina CEO Jay Flatley announced that an upgrade to their HiSeq 2000 platform expected this spring will allow users to generate 600 gigabases of sequence (the equivalent of 5 high quality human genomes) per one-week run of the machine. This would essentially double the current throughput of the platform and propel Illumina even further ahead in the arms race of delivering vast quantities of low cost sequence data. [JCB]
Over at Golden Helix, Gabe Rudy has just completed a three-part series introducing readers to the promise and challenges of new DNA sequencing technologies, which is well worth a read for those just starting out in the analysis of next-gen sequence data or who have a more-than-casual interest in the current state of the field. [DM]
This month’s edition of Trends in Genetics includes a review article on the ethical issues raised by the feedback of individual genetic data to research participants by Bredenoord and colleagues. This has long been a subject of debate, but the recent increase in studies that assay a large number of genetic variants (such as genome-wide association studies and whole-genome sequencing studies) has brought this issue to the fore. There is currently no consensus on how to deal with this, and in my experience the approach favoured has varied both between projects and between the ethics committees that have assessed them.
Continue reading ‘HiSeq doubles its output, a next-gen sequencing primer, and return of genetic data to patients’
A paper out in PLoS Genetics this week takes a step towards using genome-wide association data to reconstruct functional pathways. Using protein-protein interaction data and tissue-specific expression data, the authors reconstruct biochemical pathways that underlie various diseases, by looking for variants that interact with genes in GWAS regions. These networks can then tell us about what systems are disrupted by GWAS variants as a whole, as well as identifying potential drug targets. The figure to the right shows the network constructed for Crohn’s disease; large colored circles are genes in GWAS loci, small grey circles are other genes in the network they constructed. As an interesting side note, the GWAS variants were taken from a 2008 study; since then, we have published a new meta-analysis, which implicated a lot of new regions. 10 genes in these regions, marked as small red circles on the figure, were also in the disease network. [LJ]
23andMe customers will be interested in a neat little FireFox plug-in that allows them to view their own genotypes for any 23andMe SNP mentioned on a web page. You can download the plug-in here (you’ll need to have an up-to-date version of FireFox), and I have a brief review of the tool here. [DM]
Continue reading ‘From GWAS to pathways, the consequences of DTC genetics and screening by sequencing’
A quick note about the Reader Survey; we are going to stop taking responses at the end of Saturday (Pacific Time). If you haven’t already done so, please fill out the survey now.
A couple of interesting articles this week on the Personal Genome Project and public genomics in general. Mark Henderson at the Times has an opinion piece (behind a paywall, I’m afraid) about Misha Angrist‘s book Here Is A Human Being (see also this review from The Intersection), and in the Duke Magazine Mary Carmichael has an in-depth feature on the work of George Church, with some interesting history of the early days of the PGP.
One aspect that comes out of these articles is how those who take part in public genomics projects are starting to own the unknown unknowns. They accept that they cannot anticipate all the risks of making their data public, but are willing to take the risk of exposing themselves to these unknown risks, and in doing so turn them into knowns. Another aspect is the sheer number of individuals who want to sign up to have their data published online: 15,000 people have expressed interesting in being part of the PGP, despite initial NIH concerns the no-one would want to take part at all. This also chimes with research presented at ASHG this year, showing that members of the public are more concerned with contributing to scientific knowledge, and, crucially, getting access to their own genetic data than they are about the potential risks that such data could expose them too. [LJ]
Continue reading ‘Friday Links’
The work of geneticists, a category that includes the majority of Genomes Unzipped contributors, typically consists of analyzing DNA sequences from large collection of individuals and this constant flow of data gives us an overview of the diversity of human genotypes. And while in most cases these mutations do not have any functional impact, some rare cases are well documented and have important adverse effects.
A famous example is the BRCA2 gene for which rare mutations have been linked to an increase prevalence of breast and ovarian cancer. Another example: multiple rare variants have been linked to various forms of familial hypercholesterolemia, a condition that significantly increases heart disease risk. I picked these examples because for both cases the identification of carriers of these rare mutations in the general population could improve health: aggressive detection of breast cancer, and use of relevant treatments (such as statins) if you are a familial hypercholesterolemia patient, can make a real difference.
The fact that, in some cases at least, something can be done can put geneticists in a difficult situation. Indeed, we often come across known disease related mutations in the DNA from patients who were not recruited for anything linked to that disease. And it is not clear how this information should be handled. On one hand, we cannot assume that the patient has any desire of knowing anything about his/her disease risk. On the other hand, while analysts always work on anonymous genetic data, the medical staff that collected the sample could potentially get back in touch with the patient who donated his/her DNA. Letting DNA donors know may actually make a difference in their lives (again, this situation is rare but it happens).
Continue reading ‘Communicating genetic data to DNA donors’