January 18, 2011
Category:
Posted by Daniel MacArthur at 6:30 PM • 1 Comments
January 13, 2011
Category: carrier testing • counsyl • disease genetics • genomic medicine • illumina • next-generation sequencing • pre-natal genetic diagnosis
In the last century infant mortality has
declined precipitously in the Western world, thanks in large part to the development of antibiotics and vaccination. Yet as the suffering and death from infectious disease has reduced, the burden from genetic disease has become proportionately greater: currently around 20% of all infant deaths in developed countries are a result of inherited Mendelian (single-gene) disorders.
What can be done to reduce this burden? Increasingly sophisticated methods for detecting disease in embryos during pregnancy will help, and these have recently taken another step forward with the development of accurate, non-invasive methods based on analysing foetal DNA in the blood of pregnant mothers (an
article in the BMJ this week demonstrates the feasibility of this approach for a non-Mendelian disease, Down syndrome; and the same group showed
late last year that this approach can also be applied to effectively any known disease-causing mutation). Yet these approaches detect disease after pregnancy has already begun.
Disease mutations can also be detected in embryos prior to implantation, for prospective parents undergoing IVF. But IVF remains an expensive, arduous and invasive procedure, and thus a weapon of last resort for most parents-in-waiting; as Armand Leroi notes drily in
an exceptional 2006 article in EMBO Reports: "nature has contrived a cheap, easy and enjoyable way to conceive a child; IVF is none of these things." (While Leroi goes on to argue that the challenges of IVF are less severe for young couples with no fertility problems, it still seems fairly implausible that this will become the default mode of reproduction in the near future.)
However, for some classes of Mendelian disease it's possible to move the screening one step back. Recessive diseases are insidious things. The mutations that cause them lurk undetected - each of us carry perhaps 5 to 10 of them - as their carriers are protected by the presence of a healthy second copy of the affected gene. These mutations can thus wait silently for generation after generation, until a carrier is unlucky enough to fall for someone who carries the same mutation, or another mutation in the same gene. The children of such a couple will each have a 25% chance of inheriting one damaged copy of the gene from each parent and thus developing the disease.
The ability of a recessive mutation to pass silently from generation to generation means that many children born with recessive diseases have no family history. And while certain marriage practices (notably serial first-cousin marriage) can dramatically increase the risk of having a child with a recessive disease, these diseases can also explode into appearance in families with no obvious risk factors.
However, the fact that both parents must carry mutations in the same gene to pass a recessive disease to their children raises the possibility of detecting risk before a couple has even conceived children. For instance, one could screen both members of a couple for a panel of known mutations, an approach currently offered by US company
Counsyl (disclaimer: my wife and I both accepted free tests from Counsyl in 2009). However, while a panel containing all known Mendelian mutations
could detect a substantial fraction of all genetic disease (Leroi again), it can never eliminate the risk, because many Mendelian mutations remain undiscovered. However, one could go one step further: rather than simply look for known mutations, one could examine the entire sequence of all genes known to be associated with Mendelian diseases, and thus identify new mutations lurking in the same gene.
In
an article published today in Science Translational Medicine a group of US researchers describe a high-throughput approach for doing precisely that.
Read on »
Posted by Daniel MacArthur at 9:00 AM • 11 Comments
January 11, 2011
Category:
Software company 5AM Solutions has just launched
a neat little FireFox plug-in for customers of consumer genomics company
23andMe.
The idea is very simple:
- Download your raw data from 23andMe (or use one of the files from me or my colleagues at Genomes Unzipped);
- Install the plug-in from here and point it to your 23andMe data;
- Browse to a website discussing one of the genetic variants included on the 23andMe chip, and you'll see highlights around the rsID of any variant on the page (rsIDs are unique codes assigned by dbSNP to most of the common variants targeted by personal genomics companies);
- Mouse over the rsID and your own genotype for that SNP will appear.
For any 23andMe user who's ever come across a variant on PubMed and wondered what their own genotype was, then gone through the process of logging into 23andMe and checking, the value of this tool is immediately obvious.
Here's a screenshot using my own data:
Read on »
Posted by Daniel MacArthur at 12:00 PM • 11 Comments
January 7, 2011
Category: FDA • commercial genetic testing • diy genetics • genomes unzipped • genomic medicine • informatics • next-generation sequencing • open science • paternalism • personal genomics • personal utility • risk prediction • transparency • whole-genome sequencing
As part of his Gene Week celebration
over at Forbes, Matthew Herper has a provocative post titled "
Why you can't have your $1000 genome". In this post I'll explain why, while Herper's pessimism is absolutely justified for genomes produced in a medical setting,
I'm confident that I'll be obtaining my own near-$1000 genome in the not-too-distant future.
Matt's underlying argument is that while sequencing costs will continue to drop, obtaining a complete genome sequence that is sufficiently accurate for medical interpretation will require additional expenses (increased sequence coverage to ensure accuracy, all of the computation required to stitch the raw data into a useable form, and paying doctors to perform the interpretation) that will keep the cost of medical sequencing well above the
arbimagical US$1,000 threshold. Instead, Herper argues, we will likely see medical-grade genomes stay above $10,000, or at least above the $2,000 currently forked out for MRI scans.
There's certainly some depressing truth here. I believe Herper is right that
if you intend to access your genome sequence via a traditional medical route, it will certainly cost more than $1000 for the foreseeable future - if indeed you can get access to it at all, which is by no means guaranteed. The costs of clinical sequencing will include even more overheads than Herper notes in his short post: for instance, even as the accuracy of high-throughput sequencing technology improves, there will still be a need for variants with major medical impact to be independently validated in clinical labs, and custom assays don't come cheap.
However, many of these extra costs of clinical sequencing will be further inflated by regulatory demands (at least some of which will be arbitrary and pointless), and many will only apply if you obtain your genome through the medical system.
Individuals with the motivation to seek alternative routes will be able to obtain a perfectly serviceable genome sequence at a substantially lower price: they'll have to be cautious in how they interpret the results, of course (although, importantly, this is also true of a medical test), but it will be possible to obtain substantial and potentially extremely useful information from your own genome without having to pass through the clinical toll-booths.
The key obstacle will be the development of cheap (or free), intuitive tools for annotating large-scale genetic information. Purchasing the sequencing itself will be trivial: even if the FDA succeeds in crushing innovation in direct-to-consumer genetic testing in the US, there will be plenty of companies abroad (especially in East Asia) willing to convert a mailed saliva sample into an assembled genome sequence. What the individual needs to do with that sequence is to (1) validate that the sequence they receive is in fact their own genome; (2) extract medically useful variants; (3) confirm that these variants are real; and (4) figure out how that information should be used to make health and lifestyle decisions.
Read on »
Posted by Daniel MacArthur at 10:10 AM •
December 15, 2010
Category: anti-genism • errors • luddism • risk prediction
Late last week I stumbled across a press release with an attention-grabbing headline ("
The Causes of Common Diseases are Not Genetic Concludes a New Analysis") linking to
a lengthy blog post at the Bioscience Resource Project, a website devoted to food and agriculture. The post, written by two plant geneticists, plays a tune that will be familiar to anyone who has encountered the rhetoric of GeneWatch UK: basically, modern genomics is pure hype perpetuated by scientists seeking grant money and corporations seeking to absolve themselves of responsibility for environmental disasters.
The post is long, but its core argument can be summarised as follows:
- Genome-wide association studies (GWAS) have failed to find variants explaining much of the risk of common diseases like type 2 diabetes;
- The potential hiding places postulated for the remaining "missing heritability" are implausible;
- Many epidemiological studies have shown a major role for environmental factors in determining disease risk;
- Studies estimating the proportion of disease risk determined by genetics using twin pairs are flawed;
- Both corporations and medical researchers have incentives to prop up the notion that common diseases have genetic causes;
- Therefore, the notion of major genetic causation for common diseases is a fallacy, and we should stop looking for disease genes in favour of investing in beneficial environmental changes.
These claims would be fascinating, if true. However, while the article makes some (scattered) valid points, its central claim (that the results of GWAS suggest that genetics plays little or no role in the causation of common diseases) is entirely false, and the authors rely on a combination of distortions and statistical misunderstandings to make their case.
So, let's take a closer look at how well the some of the claims in the article stand up.
Read on »
Posted by Daniel MacArthur at 7:15 AM • 10 Comments
December 3, 2010
Category: genomes unzipped
A reminder to anyone who reads my other blog Genomes Unzipped that we have
a reader survey underway there now, which includes some questions about genetic testing experiences and attitudes towards genetics. We're closing the survey to responses this weekend, so if you're an Unzipped reader but haven't had a chance to fill in the survey, please
do so now.
Posted by Daniel MacArthur at 9:45 AM •
November 24, 2010
Category: 23andme • personal genomics
Update 30/11/10: 23andMe has extended their 80% discount until Christmas, without a need for a discount code.
Personal genomics company 23andMe has made some fairly major announcements this week: a brand new chip, a new product strategy (including a monthly subscription fee), and yet another discount push. What do these changes mean for existing and new customers?
Read on »
Posted by Daniel MacArthur at 8:45 AM • 8 Comments
October 12, 2010
Category: diy genetics • genomes unzipped • open science • participant-driven research • personal genome project • transparency
Back in June I launched a new blog,
Genomes Unzipped, together with a group of colleagues and friends with expertise in various areas of genetics. At the time I
made a rather cryptic comment about "planning much bigger things for the site over the next few months".
Today I announced what I meant by that: from today,
all of the 12 members of Genomes Unzipped - including my wife and I - will be releasing their own results from a variety of genetic tests, online, for anyone to access. Initially those results consist of data from one company (
23andMe) for all 12 members;
deCODEme for one member; and
Counsyl for two of us (my wife and I). As the project proceeds, we plan to obtain and release the results from a far wider range of genetic tests, up to and including complete genome sequences.
We have plenty more planned over the next few weeks, including discussion of the ethical issues associated with releasing data publicly, especially given the potential impact on family members. We'll also be presenting analyses of our own data: many of us are active researchers in genetics, and relish the opportunity to apply our research tools to our own genomes. We'll be releasing software code allowing others to run the same analyses on their own data.
So, why on Earth are we doing this?
Read on »
Posted by Daniel MacArthur at 8:45 AM • 10 Comments
September 30, 2010
Category: genomes unzipped
Over at Genomes Unzipped, my esteemed colleague Carl Anderson has
his first ever blog post: an exploration of the various ways in which the effects of genetic variants on disease risk can vary from person to person.
This potential variation has been the cause of much angst among critics of the direct-to-consumer genetic testing industry. However, as Carl notes, DTC testing companies generally do a pretty good job of conveying the uncertainty associated with one source of variation (differences in population background), and can't really be blamed for not accounting for the effects of environment and age given the currently weak scientific literature in this area.
However, it's worth noting that the current literature does provide some promising hints that variation in effect sizes may not be as large as originally feared. As Carl notes, one
recent study in PLoS Genetics found that genetic factors associated with type 2 diabetes show no compelling evidence for varying effect sizes between cohorts of European Americans, African Americans, Latinos, Japanese Americans, and Native Hawaiians.
Larger samples and a broader range of diseases will be required to confirm how widely this pattern holds, but it's tentatively reassuring for individuals of non-European ancestry: in most cases, risk estimates from your 23andMe data based on European cohorts will probably still be broadly applicable even if you're one of the majority of human beings who aren't descended from pallid European ancestors.
Moving forward, we can expect very large longitudinal studies (such as the half-million strong
UK Biobank) to provide more precise estimates of the interactions between genetic risk factors and environmental variables in individuals from different populations. In the meantime, the generic advice I give to all genetic testing customers applies: read everything you can, treat the caveats seriously, and take
every risk estimate as provisional and uncertain (with some being far more uncertain than others, of course!). We're still at the beginning of the genetic revolution, and uncertainty is simply the price you pay for getting in early.
Posted by Daniel MacArthur at 7:30 AM •
September 14, 2010
Category: blog admin
In my second big piece of news for the day, I'm pleased to announce that Genetic Future will shortly be moving to a
the brand new Wired Science Blogs network.
While
the network was announced today there will be a brief hiatus before I get started in my new home, due to the time constraints imposed by
my first big announcement today. However once the move is complete I'll be back to delivering the same slices of genetics and personal genomics goodness that you've been getting here at ScienceBlogs (or at least, that you
were getting before my recent exposure to the mind-shattering effects of a new baby).
Frankly I've no idea how I managed to sneak in, but I'm pleased to be in such lofty company!
I'll be back with more details of my new URL and RSS feed in the next week or so.
I wanted to thank the folks at ScienceBlogs (and particularly Erin Johnson) for the opportunity to blog here for the last two years - it's been fun.
Posted by Daniel MacArthur at 2:00 PM • 7 Comments
