Author Archive for Vincent Plagnol

Exaggerations and errors in the promotion of genetic ancestry testing



One thing we have done in Genomes Unzipped is to report on what is on the market for consumers interested in getting information about their genetic data. While we have found generally positive things to say about this market, there are also many exaggerated claims especially when it comes to making inferences about an individual’s ancestors from direct-to-consumer genetics companies. An example came up last summer with a BBC radio 4 interview of Alistair Moffat of Britain’s DNA.  This post will discuss the scientific basis of some of the claims made in the interview.

But first of all, what is my motivation to write this post? After all, there are quite a few genetic ancestry companies like Britain’s DNA, making similar claims. Why specifically discuss this BBC radio 4 interview? The main reason is that listening to this radio interview prompted my UCL colleagues David Balding and Mark Thomas to ask questions to the Britain’s DNA scientific team; the questions have not been satisfactorily answered. Instead, a threat of legal action was issued by solicitors for Mr Moffat. Any type of legal threat is an ominous sign for an academic debate. This motivated me to point out some of the incorrect, or at the very least exaggerated, statements made in this interview. Importantly, while I received comments from several people for this post, the opinion presented here is entirely mine and does not involve any of my colleagues at Genomes Unzipped.
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A review of openSNP, a platform to share genetic data

I initially came across openSNP when the team won in late 2011 the PLoS/Mendeley binary battle. This competition was open to software that integrate with Mendeley*, a suite of web and desktop tools designed to manage bibliography. So while the scope of the competition was quite broad, the winners self described their project in an interview in a way that directly relates to themes of interest to the Genomes Unzipped crew and readers. Precisely I quote:  “we try to be a community-driven platform for people who are willing to share phenotypic and genetic information for the public”. Given these aims, I decided to look into openSNP to understand what the service and aims are. I also contacted Bastian Greshake from the openSNP team who has been very helpful in answering my questions. To make a long story short, this is a fantastic idea and a great implementation, a real must-try for all users interested in the direct-to-consumer (DTC) genetic market. Keep reading for the full story.

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A personal view of genetic diagnosis using modern DNA sequencing technologies

Medical and personalized Genetics

One of my research area is the diagnosis of rare genetic conditions and in that context I collaborate with David Kelsell at Queen Mary University of London. One of the interesting cases we have analysed recently is an extremely rare condition in which the patients suffer severe chronic skin and bowel inflammation. I was in charge of the analysis of the sequence data, so for readers interested in the technical aspects here is a short overview: this was a sequencing project of pooled DNA (from three samples, only one of them relevant to this study), using a capture array to enrich for regions of the genome showing evidence of being linked to the disease. I first came across a 4 bp deletion in the ADAM17 gene, and it was rapidly identified by David Kelsell and his team as a likely cause of the disorder. Further functional work confirmed that this variant is almost certainly the disease-causing mutation.

This study was published last year and an interesting aspect is that the individual in whom this mutation was first seen is now 19 years old, doing well, and entering his second year at the University of Cambridge. Daniel MacArthur and myself met with him to discuss his thoughts and feelings about the whole experience. Continue reading ‘A personal view of genetic diagnosis using modern DNA sequencing technologies’

23andMe publishes new findings for Parkinson’s disease


The Genomes Unzipped members have spent a lot of time discussing their 23andMe genotyping data, and therefore it makes sense to follow-up on the recent scientific publications from this company. This new publication from 23andMe is particularly newsworthy because while 23andMe had already reported new findings for common traits, this is as far as I can tell the first time that a direct-to-consumer genetics company has tackled a major disease. Here, this is Parkinson’s disease (PD) a relatively common condition which has been a focus of 23andMe for a long time now. This 23andMe study identifies two new PD loci. They also replicated the vast majority of published findings, hence confirming the validity of their approach and confirming their role as a significant player in the field of common disease genetics. 

I should also mention that I was involved in a companion paper that will be published shortly in the same journal (only slowed down by technical issues, hopefully only a matter of days) and therefore my enthusiasm about this study may be somewhat biased.

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The genome hasn’t failed

On Monday, the Guardian published an article by plant geneticist Jonathan Latham entitled “The failure of the genome”. Ironically given this is an article criticising allegedly exaggerated claims made about the power of the human genome, Latham does not spare us his own hyperbole:

Among all the genetic findings for common illnesses, such as heart disease, cancer and mental illnesses, only a handful are of genuine significance for human health. Faulty genes rarely cause, or even mildly predispose us, to disease, and as a consequence the science of human genetics is in deep crisis.

[…] The failure to find meaningful inherited genetic predispositions is likely to become the most profound crisis that science has faced. [emphasis added]

The claim that human genetics is in crisis is not novel. Latham made an extended version of this argument in a blog post at the Bioscience Resource Project in December last year, which Daniel critiqued at length at the time, and which contained a schoolboy statistical error corrected by Luke. And Latham is by no means the only genome-basher out there: the 10 year anniversary of the sequencing of the human genome triggered a spate of “genome fail” pieces (see Nicholas Wade, Andrew Pollack, Matt Ridley, and a particularly horrendous example from Oliver James, for instance).

We suspect for most of our readers Latham’s rather hysterical critique will fall on deaf ears, but it is part of a bizarre and disturbing trend that needs to be publicly countered. Here are several of the places where Latham’s screed gets it patently wrong:

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People Have A Right To Access Their Own Genetic Information

This week has seen another FDA meeting seeking guidance on how to regulate direct-to-consumer (DTC) genetic tests in the US. The meeting itself has been covered by GNZ bloggers Daniel at Genetic Future and Dan at Genomics Law Report, and its apparent outcome has sparked furious debate elsewhere. The discussion among the “independent” panel convened at the meeting appeared to converge on the proposal that all health-related genomic tests should be ordered and reported through physicians. However, the outcomes of the meeting in terms of FDA policy remain unclear, and one FDA official has indicated that decisions about the availability of genetic tests will be made on a test-by-test basis.

There is no doubt that the appropriate regulation of personal genomics tests is a complex issue, and there is a diversity of opinion about how best to achieve it within GNZ (as there is throughout the genomics community). However, there are several points we agree on:

  • Individuals have a fundamental right to access information about themselves, including genetic information. While it is important to also consider the accuracy, interpretation, validity and utility of tests, this underlying principle should guide policy.
  • There is currently no evidence that DTC genetic tests pose a danger to consumers. A recent study of over 2,000 participants in DTC testing concluded that “testing did not result in any measurable short-term changes in psychological health”. In the absence of any evidence of harm there is no justification for restricting individual autonomy.
  • DNA does not have magical powers, and does not require special treatment simply by virtue of being DNA. Genetic exceptionalism – the idea that genetics must be treated as special under the law – is an inappropriate basis for policy-making. Tests should be regulated appropriately based on their predictive power, utility and potential for harm, all of which are related concepts.
  • As DNA sequencing becomes cheaper, the line between medical and non-medical testing will continue to blur. Excessive regulation of health-related genetic tests could also unncessarily hinder the ability of people to access their entire genome sequences for other purposes (such as genetic genealogy).
  • Most clinicians do not have the appropriate knowledge to interpret genomic tests, particularly in healthy individuals. This point is almost universally agreed, even by the FDA, and has certainly been the experience of some of the GNZ members upon taking our genetic results to doctors. Physicians in general are therefore a strange choice for ‘guardians of the genome’.
  • Most early adopters of DTC genetic tests are sufficiently well-informed to understand the implications of a genomic test and interpret the results correctly. Putting a general physician between these informed individuals and their own genomes is paternalistic and unnecessary.

While the outcome of the FDA’s deliberations remain uncertain, it is clear that there will be intensive lobbying against any attempt at excessive legislation. In the worst case scenario, the fledgling and innovative personal genomics market could be crushed by the FDA. However, there is still plenty of room for a measured approach that enforces test accuracy, punishes false claims and promotes informed choices by consumers, without reducing the ability of responsible companies to continue to operate and innovate.

We urge others in the genomics community to make their voices heard on these issues. Let the FDA – and, if you’re based in the USA, your political representatives – know that regulation of genetic testing should be based on evidence, not fear, and that any attempt to unreasonably restrict your access to your own genetic information is unacceptable.

Our favourite papers of 2010

To celebrate the end of the blogging year here at Genomes Unzipped, we wanted to spend a bit of time reminiscing about the papers we enjoyed the most in 2010. Feel free to add your own suggestions in the comments!

Joe: Mice, men, and PRDM9. A key goal in evolutionary biology is to identify the mechanisms leading to speciation. One way to get at that goal is to identify genes that cause sterility or reduced fitness in hybrids between species or diverged populations. In mammals, exactly one such gene has been identified to date: the DNA-binding protein PRDM9. This year, three groups working on a seemingly different problem–deciphering the molecular mechanisms by which recombination shuffles genetic variation between generations–stumbled across an important gene in this process: PRDM9. Variation in this gene influences recombination patterns in both mice and humans, and is responsible for the dramatic differences in recombination patterns between humans and chimpanzees. Is it a simple coincidence that a gene which influences recombination also appears to have a role in speciation? Time will tell.

Parvanov et al. (2010) Prdm9 Controls Activation of Mammalian Recombination Hotspots. Science. DOI: 10.1126/science.1181495.

Baudat et al. (2010). PRDM9 Is a Major Determinant of Meiotic Recombination Hotspots in Humans and Mice. Science. DOI: 10.1126/science.1183439.

Myers et al. (2010). Drive Against Hotspot Motifs in Primates Implicates the PRDM9 Gene in Meiotic Recombination. Science. DOI: 10.1126/science.1182363.

Daniel: Whole-genome sequencing to develop personalised cancer assays. The area of medicine where the transforming power of new DNA sequencing technologies is moving the fastest is in cancer diagnostics and therapy. There were many studies relevant to this field in 2010 (with a fair proportion featuring on the excellent MassGenomics blog), but this paper was a simple, elegant example: the authors performed low-coverage whole-genome sequencing of four tumour samples, identified large genomic rearrangements present in the tumour cells but not in the patient’s healthy tissue, and then designed personalised, quantitative assays measuring the proportion of cells carrying these rearrangements in the patients’ blood. These assays allowed them to track, almost in real time, how the patients’ cancers responded to various therapies, like so:

Leary et al. (2010) Development of personalized tumor biomarkers using massively parallel sequencing. Science Translational Medicine. DOI: 10.1126/scitranslmed.3000702.
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Rhesus, paternity tests and 23andMe

The story behind this post is that my wife recently gave birth to our first son and we experienced a funny story about genetics the day following the birth. Before I start I should say, to reassure the reader, that I have no doubt that I am indeed the father of my child. But as you will see, a non-geneticist might have become worried when faced with the same situation.

Firstly, my wife has a negative rhesus type. This has important medical implications because if the baby were to have a positive rhesus type, she would create antibodies against this marker which could be life-threatening for any subsequent child of positive rhesus type. Basically this is a relatively big deal, but there are ways to deal with this, and therefore knowing the blood type of the baby is essential.

The day after the birth, while we are both lying on our bed, very tired, a midwife comes by and asks us whether we know the rhesus status of the baby. We answer negatively, she checks her notes and says, “Ah, good news, the baby is rhesus negative. The father must also be rhesus negative then!” Well, I am not…

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Communicating genetic data to DNA donors

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).
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