I noticed today that GEDmatch is trying to raise funds to cover the cost of their web services. What are those services? Basically if you get raw data back from direct-to-consumer genotyping firms GEDmatch allows you to run further analytics. You can do some of these yourself…but most people aren’t going to know how to convert their files into pedigree format and use PLINK. As genotype data becomes more and more common there’ll be more need for analytic services like GEDmatch, whether for profit or for fun.
One can imagine a near future where much of the work can be offloaded to desktop applications (e.g., Promethease does this for traits and diseases). But the problem is that there is greater returns to the analysis when you aggregate the source data into huge agglomerations, and if people are doing their own analyses on their own systems that’s not going to happen (the GWAS information in Promethease uses aggregated information implicitly with the studies they rely on). This is why GEDmatch and openSNP are important.
In any case, if you have used GEDmatch and wish to give, this would be a good time.
AncestryDNA believes that our customers have the right to their own genetic data. It is your DNA, after all. So we’re working to provide access to your raw DNA data in early 2013, which includes related security enhancements to ensure its safety during every step of the process. Moving forward, we plan to add even more tools and improvements for our customers, and any new features will be available to all AncestryDNA members.
If the rights of the customers to own their own data were so important to them they should have front-loaded this feature. As it is, they didn’t, and as many bloggers noted the firm had stated they didn’t have plans to unroll this feature in the near future. What changed? I don’t know the details, but I suspect they realized that many of us who complained in the past were going to continue to complain constantly. Combined with the contrast with its competitors, like 23andMe, and I assume they realized this just wasn’t going to solve itself if they ignored it. The key here is follow up. I’ll assume “early 2013″ is no later than March 31st (the first 1/4th of the year). If AncestryDNA doesn’t have the feature out by then I’ll assume they’re not serious, and will begin trying to make sure that their deficits come up high on Google searches again.
Blogs and word of mouth matter a lot in this domain. I convinced James Miller, author of Singularity Surviving, to get his parents genotyped this weekend. Also, after more than two years of harassment a friend who works at Google finally got typed, and will be sending me his data.
Less than a month ago I pointed to the release of ADMIXTOOLS. Unfortunately, though I have a desktop at home devoted purely to my personal genomic hobbies I haven’t been able to free up the time on weekends to start doing my own analysis. This is pretty pathetic, and sometimes I get a little depressed at how little usage there is of all the great scientific software released into the public domain. But in case you haven’t seen it, I want to point you to Dienekes Pontikos’ posts using ADMIXTOOLS. Frankly, my personal experience with this sort of thing tells me to hold off on any judgement until I’ve used the software package and gotten a feel for its tendencies. But until those of us with aspirations manage to get some blocks of time together Dienekes has the field all to himself.
John Hawks points me to a critique of NPR coverage of personal genomics. In defense of NPR they seem like Physical Review Letters in comparison to other media, such as the BBC. But I do wonder what the causality here is. Does the media lead us to the proposition that “genetics is scary”? Or is it the public which demands these stories?
Meanwhile, as some are expressing worry, technology keeps pushing forward:
A faster DNA sequencing machine and streamlined analysis of the results can diagnose genetic disorders in days rather than weeks, as reported today in Science Translational Medicine.
Up to a third of the babies admitted to neonatal intensive care units have a genetic disease. Although symptoms may be severe, the genetic cause can be hard to pin down. Thousands of genetic diseases have been described, but relatively few tests are available, and even these may detect only the most common mutations.
I got a notification today from Ian Logan that he set up a page on my genotype using a method which detects rare homozygous SNPs in the ~1 million markers I put up from my 23andMe results. My raw data is online, so anyone can analyze it. Here is the summary of my results:
The program finds about 50 ‘rare/uncommon’ SNPs from the 900,000+ tested by 23andMe.
The are no ‘homozygous-recessive’ results (surprisingly, as 1-2 might be expected).
There are a list other individuals, and sure enough most of them do have a rare recessive homozygous locus or two. I assume that ascertainment bias (the technology finding variation in Europeans better than non-Europeans in most cases) wouldn’t result in my case, because I should have less variation, not more (less variation would presumably result in more homozygous recessives). So I am thinking it may simply be that because I’m from a population with greater genetic variation (South Asians) I am less likely to yield a homozygous recessive.
I re-emphasized to John the importance to the genetic genealogy community that AncestryDNA release our genetic data to us. I mentioned that my colleagues and I were happy to discover that Ken Chahine’s statements to the Presidential Commission for the Study of Bioethical Issues in Washington D.C. on August 1st were in line with our belief that our genetic data belongs to us (video and transcript). During the second session, Dr. Chahine stated that “the customer retains ownership of their DNA and data”. However, we feel that AncestryDNA’s policies do not currently reflect this. John reiterated what I have been told before, which is that they are genuinely considering the best way to deliver this data to us. In response to my persistence, John told me that they are aware that this is important to me, but that they have to take into consideration everyone’s feedback, not just mine. As a result, giving us access to our genetic data is not at the top of their list of priorities. He explained that they read lots of feedback and do a significant number of surveys and focus groups in order to determine what is most important to their customers and, by that process, their priorities are dictated….
Slate reposts a piece from New Scientist, Do You Really Want To Know Your Baby’s Genetics? It is arranged as a series of questions which might arise from the new information. For me my frustration with this sort of discussion is rooted in reviewing old articles about “test-tube babies” in major newspapers from the 1970s and early 1980s. Today in vitro fertilization is banal and commonplace, but many of the same concerns were voiced back then which you see cropping up now in regards to personal genomics. My issue is not concern as such, but its inchoate character. It is not uncommon for me to encounter people pursuing postgraduate work in science who express the opinion that “it’s scary,” the “it” being genetic information. When further queried the fear is generally layers upon layers of formless disquiet, some confusion about the specific details, as well as a default stance toward the “precautionary principle.”
Interesting story in The New York Times, Genes Now Tell Doctors Secrets They Can’t Utter:
One of the first cases came a decade ago, just as the new age of genetics was beginning. A young woman with a strong family history of breast and ovarian cancer enrolled in a study trying to find cancer genes that, when mutated, greatly increase the risk of breast cancer. But the woman, terrified by her family history, also intended to have her breasts removed prophylactically.
Her consent form said she would not be contacted by the researchers. Consent forms are typically written this way because the purpose of such studies is not to provide medical care but to gain new insights. The researchers are not the patients’ doctors.
But in this case, the researchers happened to know about the woman’s plan, and they also knew that their study indicated that she did not have her family’s breast cancer gene. They were horrified.
“We couldn’t sit back and let this woman have her healthy breasts cut off,” said Barbara B. Biesecker, the director of the genetic counseling program at the National Human Genome Research Institute, part of the National Institutes of Health. After consulting the university’s lawyer and ethics committee, the researchers decided they had to breach the consent stipulations and offer the results to the young woman and anyone else in her family who wanted to know if they were likely to have the gene mutation discovered in the study. The entire family — about a dozen people — wanted to know. One by one, they went into a room to be told their result.
“It was a heavy and intense experience,” Dr. Biesecker recalled.
Around the same time, Dr. Gail Jarvik, now a professor of medicine and genome science at the University of Washington, had a similar experience. But her story had a very different ending.
She was an investigator in a study of genes unrelated to breast cancer when the study researchers noticed that members of one family had a breast cancer gene. But because the consent form, which was not from the University of Washington, said no results would be returned, the investigators never told them, arguing that their hands were tied. The researchers said an ethics board — not they — made the rules.
Dr. Jarvik argued that they should have tried to persuade the ethics board. But, she said, “I did not hold sway.”
By now you have probably read in The New York Times, or on the blogs, about the new paper in Nature which reports on the empirical trend toward the children of older fathers carrying more de novo mutations. Really all you need is this figure:
Obsession. I’ve been obsessed with many things in my life, from specific women to sundry topics. But I’ve never known obsession until I had a child. Perhaps others are not like me, but the monomaniacal need to know as much as you can about your future child as soon as possible gripped me early on. Even today I want to know as much about her as I can. This is why I had her genotyped at two months, and this is why I plan to have her whole-genome sequenced as soon as it is feasible. This doesn’t mean that I put much stock in the power of individual prediction. Rather, even if the returns are marginal even the smallest tidbit of knowledge about my child is precious to me.
This is why I’m left scratching my head when I see pieces which moot concerns about whole-genome sequencing of fetuses. Obviously some people will go for it, and some people will not. It won’t be very cheap, nor will it frankly tell you that much on a per base pair basis as a function of the cost. But it will tell you something, and depending on the coverage (ergo, how accurate the sequence is going to be at the end of the day) you keep the information you get. Imagine, for example, that it would cost $5,000 for 10X coverage. Would you go for it? I would. Why? How much does the average American car cost? $30,000 dollars. A car is very useful, but it’s a depreciating asset. A genome will never depreciate, it won’t degrade. In fact, as more research gets done its utility will only increase! If people are willing to pay >$5,000 for a high end gaming box, and not be perceived as crazy, why should genophiles be seen to be wild-eyed weirdos?
Of course the natural objection is that I’m discussing a problem which doesn’t exist. I wish this were so, but there’s a whole bioethics industry whose bread & butter is to trade in flimsy and specious reasoning, which might appeal to politicians who are will to purchase specious reasoning for purposes of their demagoguery. For example, As Prices for Prenatal Genome Sequencing Tests Fall, Researchers Worry About Consequences for Families in a Real-Life ‘Gattaca’:
At this point if you have spare cash why not shell out $300 for a raw copy of your genotype? (yes, I know 23andMe provides other services) I’m sure many readers spend $100 on nice meals now and then. That’s one day. Your genotype won’t ‘depreciate’ in a literal sense, and more practically until whole-genome sequencing gets affordable within the next decade (i.e., < 10 years) 1 million SNPs is a pretty good deal. And not to be morbid, but it is probably best to get older family members typed now (though if they have had hospital stays you can probably later retrieve genetic material, it will be a bureaucratic pain).
The reason I’m posting this now though is that I received a notification about a $50 discount code from 23andMe. Here it is: YHPRD7. It’s valid for the next few days. $50 isn’t trivial for most people, so perhaps it will prompt a few here to go and purchase.
It’s easy to see genomic data regulation in romantic narrative terms — The plucky little guys who want to be free! The big, bad institutions who want to control them! — and it’s also a trap. Interpreting genomic information in a medically useful way is very, very complicated. It’s easy to do badly — and people may make life-altering decisions based on bad information.
Gene-testing companies already have a track record of offering tests unsupported by unsupported by clinical evidence, such as CYP450 testing to determine antidepressant dosage. A let-the-market-regulate-itself, buyer-beware approach isn’t any more desirable than it would be for new drugs.
We’re discussed this before. The shorter perspective from me is that on principle I don’t object to regulation, but when viewed across the constellation of things which our government regulates, I don’t see the case for direct-to-consumer genomic services being monitored closely. A result from 23andMe will not kill you, though it may lead to a sequence of actions which may kill you. But this is unfortunately a problem with the whole diet industry, which is often based on unsupported fads and fashions, and has a much larger social impact. Nutrition is very complicated with incredible real life consequences, and yet regulating it would frankly be a fool’s errand. You may destroy the American diet publishing industry, but you can’t prevent internet message boards. Similarly, the SNP-chip results themselves are commodities, and with client and server analytic software proliferating in the next few years the reality is that the market will regulate itself! And unfortunately, the impact on peoples’ lives will be the same, for good or bad, as the diet industry.
Article in The New York Times:
Genetic testing raises some vexing ethical questions, like whether it will cause unnecessary anxiety or lead to more medical procedures, including abortions.
Now, as the number of tests and the money to be made from them are exploding, another question is being asked by professionals in the field themselves. Is it ethical for genetic counselors, who advise patients on whether to undergo testing, to be paid by the companies that perform the tests?
While it might not always be immediately obvious to patients, some counselors offering them advice in hospitals and doctors’ offices work for the commercial genetic testing companies, not for the hospitals or doctors themselves.
Conflict of interest in anything medical is pretty bad. On the other hand, medical care is expensive. But I want to add something here: the pre-natal screens by Genzyme are really, really, bad value-for-cost. For example, a non-insurance “sticker price” of thousands of dollars for 200 traits. Speaking from personal experience here. Also, don’t think you can ever get genetic material sent to Genzyme back. I called and tried this for a few months, and there was no response (I wanted to do typing of tissue myself).
So they don’t. Instead, they buy a $100 test kit, they each provide a small blood sample and send it off to one of the companies offering fetal genome testing. At the testing lab, they can separate out the mother’s DNA from that of the fetus, both of which are present in the mother’s blood. By comparing the fetal genome to the mother’s and father’s, it’s easy to spot de novo mutations. If a certain gene doesn’t match either the mother or the father’s sequence, it’s mutated.
A few days later the results are back. There are several mismatches detected. Most are benign – they’re not predicted to have any biological effects. But there’s one, a deletion of a few thousand bases in a gene involved in brain development. This deletion is predicted to raise the risk of epilepsy and autism from 1% to 10% apiece. The parents now have a decision to make. The mutation is a one off, it’s not inherited. If they conceive again… roll the dice again… and it’ll be gone. Do they terminate?
Like the adverts say, “Some people disagree with this, but we say there’s only one person who really matters: your baby.”
Before Birth, Dad’s ID. Nothing too surprising, if you can check for fetal abnormalities, it shouldn’t be too hard to ascertain paternity. Two issues of note in the piece. In the specific cases highlighted the author and the sources emphasized that unambiguous paternity reduced the stress of the expectant mother. But this seems like a double-edged sword. Of course that’s ultimately irrelevant, the technology and the procedure will probably become ubiquitous, because prenatal screening will become ubiquitous. Unless the analytic software is specifically designed to obscure paternity, it should simply drop out of the data as next generation genomic medical methodology attempts to phase and assess identity by descent of the in utero fetus. But the broader is the nature of parenthood itself. Rather than being legalistic or dogmatic, I think that a casuistical mode of assessment probably works best.
Finally, much of our customary law and tradition implicitly or explicitly assumes that father is at best probabilistic, while motherhood is assured. This prior condition no longer holds, so some of the laws should probably be updated. Ultimately exact knowledge of paternity is probably going to be a force for “good” rather than mischief. Last I checked paternity testing clinics catering to men who suspect they’ve been cuckolded actually only come back with a 1/3 positive result for cuckoldry. The evolutionary reasons for exhibit a “false positive bias” here are clear, but we don’t need to rely on instinctive heuristics when the truth can set us free.
Addendum: If you are a member of the cuckold-community, or, are an men’s rights activist, I’m going to delete your comment. Not interested in bizarre fantasies or anger.
Evolution’s winner. Real headline.
In the mid-2000s two British biologists of some public note attempted to revive or resuscitate the good name of eugenics, Richard Dawkins and Armand Leroi. My own suspicion is that this emerges in part from a implicit cultural history in the British Isles in regards to eugenics: in those nations,* unlike in the USA or Germany, eugenics was generally conceived of in the positive rather than negative sense. By this, I mean that a disproportionate amount of thought was given to the procreation of the favored, rather than coercive restriction of the unfit. This is exemplified by R. A. Fisher, the co-founder of both evolutionary genetics and statistics, who worried about the high mortality rate of the British elite during World War I. Fisher himself went on to have eight children, a situation which occasionally left him in financial distress, as would be predicted from standard Malthusian assumptions (see R.A. Fisher: The Life of a Scientist).
Analysis of cell-free fetal DNA in maternal plasma holds promise for the development of noninvasive prenatal genetic diagnostics. Previous studies have been restricted to detection of fetal trisomies, to specific paternally inherited mutations, or to genotyping common polymorphisms using material obtained invasively, for example, through chorionic villus sampling. Here, we combine genome sequencing of two parents, genome-wide maternal haplotyping, and deep sequencing of maternal plasma DNA to noninvasively determine the genome sequence of a human fetus at 18.5 weeks of gestation. Inheritance was predicted at 2.8 × 106 parental heterozygous sites with 98.1% accuracy. Furthermore, 39 of 44 de novo point mutations in the fetal genome were detected, albeit with limited specificity. Subsampling these data and analyzing a second family trio by the same approach indicate that parental haplotype blocks of ~300 kilo–base pairs combined with shallow sequencing of maternal plasma DNA is sufficient to substantially determine the inherited complement of a fetal genome. However, ultradeep sequencing of maternal plasma DNA is necessary for the practical detection of fetal de novo mutations genome-wide. Although technical and analytical challenges remain, we anticipate that noninvasive analysis of inherited variation and de novo mutations in fetal genomes will facilitate prenatal diagnosis of both recessive and dominant Mendelian disorders.
Here’s the last paragraph:
As a follow up to my post below on the thick coverage of European information in genealogical and genomic databases, here are the “Ancestry Finder” matches from 23andMe for my daughter using the default settings:
If I increase sensitivity India does come up, at 0.1%, second to last in a very long list of European nations. I’m pointing this peculiarity out because my daughter is 50 percent South Asian, but this element of her ancestry doesn’t find many matches because there aren’t many people out there in the database to match. In contrast, because she is 1/8th Norwegian (her great-great grandparents were immigrants from the Olso area; thanks Ancestry.com!) this “block” jumps out, and aligns up with many people in their database.
This isn’t just an exceptional case. Here’s the result for a friend who is 50 percent East Asian (Chinese) and 50 percent American white:
The old warning rears its ugly head: the tool is just a tool, and must be used with and understanding of what it can and can’t do. If you decrease sensitivity many South Asians actually match people from European nations before they do people from India. Why? Part of it is probably that many South Asian groups are highly endogamous, which dampens intra-South Asian segment sharing. And the other part is that the sample size of Europeans is so large that random matches with this population are just as, or more, likely than genuine matches with the smaller number of South Asians.
I follow CeCe Moore’s blog posts on scientific genealogy pretty closely. But it’s more because of my interest in personal genomics broadly, rather than scientific genealogy as such. My own knowledge of my family’s past beyond the level of grandparents is very sketchy. This despite the fact that I know I have two very well documented lines of ancestry which I could follow up on, my paternal lineage, and the paternal lineage of my mother’s maternal grandfather. I don’t have a great interest in this beyond the barest generalities, and my parents tend to have a rather disinterested stance as well. Why? I can’t help but wonder if part of the issue is that unlike many South Asians my family has a relatively diverse background, so it isn’t as if we are sustained by a coherent self-identity as members of a sub-ethnicity (Bengalis are not tribal, so lineage groups are more ad hoc and informal). Additionally, there is probably some self-selection in the type of personalities who would transplant themselves across continents and are willing to spend the majority of their lives in a nation not of their birth.
For genetic genealogy buffs, I highly recommend Gedmatch. It’s been rolling out a lot of new features, including ancestry inference tools from the major genome bloggers. Here is my “chromosome paining” using Zack Ajmal’s reference populations: