human genome

Director of the NIH, Dr. Francis Collins Delivers at X-STEM

carlyo — Wed, 16 Jul 2014 17:22:10 +0000

Director of the NIH, Dr. Francis Collins Delivers at X-STEM

On April 24, 2014, an exclusive group of visionaries presented to over 4,000 students at the USA Science & Engineering Festival's inaugural X-STEM Symposium sponsored by Northrop Grumman Foundation and MedImmune. The all day event included interactive presentations and workshops with some of the top scientists and engineers in the country.

Geneticist and Physician Dr. Francis Collins, Director of the National Institutes of Health, captivated crowds with his journey to the NIH.

Watch his presentation below:

http://youtu.be/o214CyMbJ2c?list=PLFxuEWfG5k6F2dH21LFhUCD7jYcLOLm4C

After being nominated by President Obama, and confirmed by the U.S. Senate, to head the NIH— the nation’s top governmental agency responsible for conducting and overseeing medical research and programs designed to improve the health of the nation – Francis has been focused on leading the NIH’s 27 institutes and centers which together employ 18,000 people. The agency has a budget of $31 billion, about 80 percent which is distributed to scientists elsewhere for research. One look at Francis’ formidable career accomplishments and you will know why he was picked for such an important, high-profile position. Among his achievements:

• While involved with the Human Genome Project, Francis developed an important technique for identifying genes and went on to identify those involved in cystic fibrosis and neurofibromatosis, among other conditions. He was the first director of NIH's National Human Genome Research Institute.

• In recent years, he has been a champion of "personalized medicine," which he hopes to harvest the fruits of the genomics revolution in the form of better and safer clinical care.

• Francis spearheaded the federal government's efforts to finish the sequencing of the human genome before it could be completed by J. Craig Venter, a former NIH scientist who took on the task from the private sector. The two finished a draft of the sequence in a cooperative dead heat celebrated in a White House ceremony with President Bill Clinton in June 2000.

• While at Yale following his medical residency, he developed a technique called "positional cloning" that helps biologists locate genes scattered through the huge, linear mass of DNA. However challenging his duties are as NIH chief and scientist, Francis, with his boyish mop of (now graying) blond hair, still knows how to have fun. He is a guitarist and vocalist for "The Directors," a rock band comprised of NIH scientists and executives plays about three gigs a year.

Thank you to Dr. Francis Collins for participating in the X-STEM Symposium!

Learn more about the X-STEM Symposium by clicking here.

carlyo Wed, 07/16/2014 - 13:22

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USA Science & Engineering Festival

X-STEM

Careers in Medicine

Dr. Francis Collins

human genome

National Institutes of Health

Unruly DNA

jtoney — Fri, 24 Feb 2012 10:38:25 +0000

Unruly DNA

(Not Really) the Last Word on DNA from Virginia Hughes on Vimeo.

Science writer Virginia Hughes brilliantly explains how DNA is packed into our cells using animation.

jtoney Fri, 02/24/2012 - 05:38

Tags

Animation

human genome

science communication

Video

Bad Science: Genetic Signatures of Centenarians

jtoney — Fri, 22 Jul 2011 11:34:17 +0000

Bad Science: Genetic Signatures of Centenarians

Source.

A newsworthy study about a genetic signature of centenarians published in Science has not stood up to scrutiny by the blogosphere and peer scientists and has now been formally retracted by the authors.

Until recently, such retractions - whether by Editors or by the authors themselves - have been quite rare. With the blogosphere and 24/7 news media becoming more and more prominent, I suspect that we may begin to see more examples. Ultimately, it is a healthy process and good for science.

Below is an excerpt, with my emphasis, from their Letter to Editor in Science:

...we discovered that technical errors in the Illumina 610 array and an inadequate quality control protocol introduced false-positive single-nucleotide polymorphisms (SNPs) in our findings. An independent laboratory subsequently performed stringent quality control measures, ambiguous SNPs were then removed, and resultant genotype data were validated using an independent platform. We then reanalyzed the reduced data set using the same methodology as in the published paper. We feel the main scientific findings remain supported by the available data: (i) A model consisting of multiple specific SNPs accurately differentiates between centenarians and controls; (ii) genetic profiles cluster into specific signatures; and (iii) signatures are associated with ages of onset of specific age-related diseases and subjects with the oldest ages. However, the specific details of the new analysis change substantially from those originally published online to the point of becoming a new report. Therefore, we retract the original manuscript and will pursue alternative publication of the new findings.

Their retraction emphasizes the importance of good controls in any experiment as well as reliable statistics. Interestingly, scientists at 23andme reported problems with this study in a blog post only six days after the original publication of the study in question.

Here's an excerpt, with my emphasis:

There are several reasons for skepticism about these new results. Another recent genome-wide study has reported no significant associations with longevity. There is suggestive evidence of genotyping quality control problems in the new results, and some routine quality control checks do not appear to have been done. The design of the study is particularly susceptible to introducing biases into the results. And a preliminary analysis of the proposed 150-SNP model for predicting longevity indicates that it is not predictive in the 23andMe community.

We repeated our analysis restricted to individuals with European ancestry. The results were similar: for 129 customers with age â¥ 95 and more than 43,000 controls, we got a test statistic of 0.534, and for 26 customers with age â¥ 100, we got a value of 0.558. In both cases, the 95% confidence interval includes 0.5.

This retraction does not prove that there is no genetic component to living a long, healthy life. It is, however, an important example of how the blogosphere and fellow scientists are a key element in peer review and that science is always self correcting.

jtoney Fri, 07/22/2011 - 07:34

Tags

human genome

Media

science communication

Could Myriad Benefit If They Lose Their Case?

jtoney — Wed, 06 Apr 2011 07:03:21 +0000

Could Myriad Benefit If They Lose Their Case?

Source.

Bioephemera provided an excellent overview of the ongoing appeal to the "Myriad gene patent case."

Jessica Palmer wrote:

Myriad Genetics's patents on the breast cancer genes (BRCA1 and BRCA2) were invalid because genes are unpatentable products of nature.

Could Myriad Benefit If They Lose Their Case?

I believe that if Myriad and the biotechnology industry itself embraces open innovation, that ironically they could indeed benefit. Let me explain.

A review in Science stated (April 2010):

A legal bombshell hit the biotech world last week: A federal judge in New York City used sweeping language to invalidate a handful of human gene patents, casting doubt on hundreds more. The decision applies only in New York state and is sure to be appealed--a process that could take years. Still, it undercuts the idea that DNA sequence can be owned.

My response, published as an E-Letter in Science described how Myriad could actually benefit if they lost their case:

Doctrine of Equivalents Driving Research?

Responding to court rulings such as the one reported in E. Marshall's News of the Week story ("Cancer gene patents ruled invalid," 9 April 2010, p. 153), scientists interested in studying a patented gene often resort to strategies such as selecting minor variations of the original gene's sequence--for example, by mutating several DNA bases. In doing so, the doctrine of equivalents as articulated by U.S. patent law becomes the lynchpin regarding how basic research is done. The same scientific acumen applied to navigating around patents could be applied to the next discovery. The federal court decision regarding Myriad, if upheld, could foster incentives from an open innovation system that not only benefits the public but, ironically, private industry, including Myriad.

So, what should drive research? Should it be patent law, the "doctrine of equivalents"? Legal cases such as Myriad could serve as a turning point for scientists to embrace open innovation, liberating them from the constraints that patents can impose. To become profitable, industry itself would have to redefine how they share their information and how incentives are shared amongst the key stakeholders, including scientists, consumers and manufacturers.

Is this possible, or is it a pipe dream?

jtoney Wed, 04/06/2011 - 03:03

Tags

âIs this possibleâ

Why not? Intervening in our economy's progress and innovation systems with patents is like prescribing a powerful side-effect laden medicine and, at least in some areas, I think we may have been the victims of quackery.

Is this possible, or is it a pipe dream?

I think it's necessary.

I think you can't patent natural DNA sequences anymore than you can patent a mineral such as silver.

You can mine the silver, you can resell it, you can trade it, and you can use it as a resource to make other, marketable stuff, but no one owns a patent on silver itself.

So I say DNA should be viewed as a naturally occuring resource. You can charge others to locate, manipulate, and resell it, and, more significantly, you can use it to manufacture a unique, patentable product, but you cannot yourself hold a patent on it.

I have several reasons for thinking this.

1. You didn't create it. You may have discovered a particular sequence, but you didn't create it. It's not a product you created. Again, it's a resource you found, not a an invention of your own.

2. When you patent DNA you tread on the turf of claiming a patent on a lifeform. You are claiming a patent on life itself. I think humans would be very wise to not jump into that morally questionable territory. The potential for very nasty fallout from claiming to own another organism's life is quite high. In fact, has a legal precedent ever been set deciding whether an individual "owns" his own life? Even if he did, could he then resell it for a profit? It gets into real wobbly territory, real fast.

3. The overall effect will be to stifle research and innovation, as you have already pointed out.

There is a better way.

The way of patenting life is ugly, morally reprehensible, and leads to very bad problems later on down the road.

Let's take the high road while the science is still in its infancy, so as to make it much more difficult for those with less pure intentions later in the century.

I support whatever benefits large corporations. Humans do not count.

So, what should drive research?

Money. Nothing else but money. Money is all that matters. It's all about the money.

Money.

The irony is that (large) corporations don't necessarily benefit from the strong IP rights regimes which they - more to the point, their erm... economically naÃ¯ve in-house IP professionals - invariably advocate and lobby for. The âregulatory capturersâ have unwittingly been captured from within themselves. For example, both US and EU database companies lobbied for IP rights in databases. The EU got them, the US didn't. http://www.ft.com/cms/s/2/99610a50-7bb2-11da-ab8e-0000779e2340.html#axz…

More Friends, More Liberal?

jtoney — Thu, 30 Dec 2010 12:17:46 +0000

More Friends, More Liberal?

Photo source.

As you prepare for your New Year's celebration, here's something to consider: researchers have found that having more friends may play a role in whether you identify yourself as a liberal or a conservative.

How did they determine this?

The researchers studied a group of about 2,000 adolescents with different variants of the dopamine receptor ("allele 7R"). The dopamine receptors in our brain are associated with pleasure, cognition, memory, learning and fine motor control to name a few key functions, and the "allele 7R" has been linked to "novelty seeking behavior." They wanted to test whether having this gene is an indicator of how one self identifies with a given ideology.

The work from groups at Harvard University and University of California at San Diego was published in The Journal of Politics {you can access the paper at this link} in October and was discussed in some news media outlets such as The Washington Post, citing:

The researchers speculate that having that the gene may make people more interested in seeking out new experiences, including learning about the points of views of their friends, exposing them to a "wider diversity of viewpoints" and leading to their liberalism.

The news media described their speculation. I wanted to take a look at the data, summarized in this Figure:

Seems pretty clear, right? To quote from their study {my emphasis added}:

Holding all else constant, for people who have two copies of the allele, an increase in number of friendships from zero to ten friends is associated with increasing ideology in the liberal direction by about 40% of a category on our five-category scale. In other words, 10 friends can move a person with two copies of the 7R allele almost halfway from being conservative to moderate or from being moderate to liberal.

I wonder whether the distribution of these alleles in the US tracks with political maps? I wonder how many alleles I have, not to mention my friends and family. Perhaps that is a question for another day. Regardless, you may want to count your friends.

jtoney Thu, 12/30/2010 - 07:17

Tags

human genome

Media

Politics

Neanderthals' Cousins, Not the Fockers: the Denisovans

jtoney — Wed, 22 Dec 2010 16:03:25 +0000

Neanderthals' Cousins, Not the Fockers: the Denisovans

David Reich/Nature
The entire genome of the Denisovans was extracted from a tooth and finger bone.

The film "Little Fockers" is coming out this week, and I look forward to brilliant performances from Robert DiNero, Ben Stiller, Dustin Hoffman and Barbra Streisand to name a few. If you will excuse my cheekiness, I thought of this dysfunctional family when I learned today of the "Denisovans". Let me explain.

The human tree of life appears to have a new branch: cousins of the Neanderthals, the "Denisovans". The New York Times reporter Carl Zimmer has had a busy week. First, he reported on a paper in the Proceedings of the National Academy of the USA of the largest collection of DNA evidence of Neanderthals revealing a social structure that could include cannabilism and sharing of females from different tribes. Now, today, he reports on a paper in Nature that describes a new branch of the human family tree. Prof. Paabo from Germany has once again led a groundbreaking study in the early genetic history of humans!

The cousins' name derives from the Denisova cave in Siberia. According to the abstract from the Nature paper published today (my edits):

Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4-6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population 'Denisovans' and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans.

According to Carl Zimmer's article to be published tomorrow in The New York Times:

Dr. Paabo and his colleagues immediately set about to collect all the DNA in the Denisova finger bone. Once they had sequenced its genome, they sent the data to researchers at Harvard Medical School and the Broad Institute in Cambridge, Mass., to compare with other species.

The Massachusetts scientists concluded that the finger bone belonged to a hominin branch that split from the ancestors of Neanderthals roughly 400,000 years ago. Dr. Paabo and his colleagues have named this lineage the Denisovans.

In the early days of such research, about ten years ago, there was much controversy about the possible contamination of DNA from the scientists' handling the ancient samples, which could confuse data analysis. However, Paabo's group has mastered the art of "clean techniques" to allow the startling results that are coming out at a rapid pace in this decade. At that time, the idea of sequencing an entire genome of more than 3 billion base pairs was a far fetched dream. Now it is common place, even for sampes that are 400,000 years old! Science is grand.

Understanding our past, our social structures, diet, climate and breeding could guide our future, if we are willing to listen. No, it won't prevent dysfunctional families - perhaps that is hard wired in our genome too? Just a thought for the Holidays.

jtoney Wed, 12/22/2010 - 11:03

Tags

evolution

human genome

Didn't just contribute to Melanesians, they must have entered the gene pool of Oklahomans, too -
http://scienceblogs.com/pharyngula/2010/12/when_did_oklahoma_start_elec…

Clam's comment is grossly unfair to Melanesians. PZ Myer's suggestion of the genus asinus for the Oklahama politician is probably closer.

Cannibalism. Cannabilism is probably eating Cannabis.

Since the Denisovian species was found only in a single
specimen from a single site in Siberia, doesn't it make you wonder how many other species of man there might have been that fell by the wayside?

Neanderthals Cannibals?

jtoney — Mon, 20 Dec 2010 18:35:11 +0000

Neanderthals Cannibals?

In a stunning finding, scientists found evidence in northern Spain of cannibalism by Neanderthals. Some 1,800 bone fragments were used for DNA analysis to support their hypothesis. According to The New York Times report,

Spanish scientists who analyzed the bones and DNA report the gruesome answer. The victims were a dozen members of an extended family, slaughtered by cannibals.

It seems common knowledge that Neanderthals were lacking in refinement by modern standards, but this is a bit much. This is indeed "food for thought", since there is evidence that part of our genome is inherited from Neanderthals.

So, whether we like it or not...

It’s official – each of us is part Neanderthal. Yes, I know – some would say that they have already dealt with someone whose behavior can seem to be Neanderthal-like. The first draft of the Neanderthal’s genetic blueprint, or genome, has recently been reported and gives new insight into our deep ancestry. Early modern humans and Neanderthals are believed to have diverged into two distinct species between 270,000 and 440,000 years ago.

What can we learn from the new genetic information?

Using 21 samples of Neanderthal bones collected in Croatia, dated more than 38,000 years ago, scientists found that our genetic makeup is 99.84% identical to that of Neanderthals; for comparison, 96% of our DNA is identical to that of chimpanzees. The tiny difference of 0.16% includes some fascinating detail, such as genes that regulate metabolism – critical for appetite and diet - as well as genes involved in skin, skeleton, and the development of cognition, necessary for higher learning.

That our genetic background is closely related to our ancient ancestors is not surprising. However, this study gives definitive evidence for the first time that early modern humans and Neanderthals interbred with our ancestors in Europe and Asia. An estimated “mixing” between the two species of about 2% was revealed from the genetic data. This discovery is a departure from the classic “Out of Africa” theory that the human race began in Africa.

In 2004, I had the pleasure of visiting the laboratory of the lead scientist of this discovery, Prof. Svante Pääbo at the Max Planck Institute for Evolutionary Anthropology located in Leipzig, Germany. At that time, his description of their hopes to sequence the complete genome of a Neanderthal seemed far-fetched and exciting. Prof. Pääbo says that “They live on in some of us” – indeed, perhaps in all of us. This should give all of us pause whenever we find ourselves believing that humans are somehow special amongst the vast diversity of species that live on this planet.

To learn more about this discovery, I highly recommend the following:

•Science podcast, as well as a superb overview, including video, produced by the American Association for the Advancement of Science.

A version of this article was originally published on NJ Voices.

jtoney Mon, 12/20/2010 - 13:35

Tags

evolution

human genome

Technology

FWIW, scanning my feed reader, I thought the title of this post was "Neanderthals Cannabis?"

Mind you, I'm not disappointed, just momentarily confused.

Carl Zimmer recently posted a nice audio overview of current Neanderthal research. So I thought I was caught up. But cannabis! Okay, cannibals. Oh, well.

Who were the Cannibals? Were they fellow Neanderthal?
I'd believe Homo Sapien Sapiens more prone to hunt and eat them as modern human tribes are known into modern era to eat other humans.

Big deal! Cannibalism has always been present in some human societies. Just look at some findings from old Anazasi sites.
As for starvation canibalism, it is with us even today, as distinct from culturally approved canibalism.
And what about humans who make lamp shades from human skins? That was not long ago...

The New York Times reporter Carl Zimmer wrote: "The victims might have wandered into the territory of another band of Neanderthals. For their act of trespass, they paid the ultimate price." Of course, this is conjecture based upon the DNA evidence found in the bone samples, some 50,000 years old.
According to Dr. Todd Disotell, an anthropologist at New York University, this âgives us the first glimpse of Neanderthal social structures.â

Wow -- you seem stunningly unaware of the massive amounts of evidence of at least episodal canibalism among modern humans, ranging from NG cultural material, to Anazasi remains to Central Mexican corpses to European cannibalism pits, to anti-prion genetic defenses widespread among modern humans.

What would be shocking would be to discover that Neanderthal's were never cannibalistic.

And this "each of us is Neanderthal" -- your Eurocentrism is showing, dude. Australian aborigines are unlikely to be significantly "Neanderthal" -- nor Kung San Africans.

Right. The adjective "gruesome" is utterly unwarranted hyperbole (ditto the silly conjectures in the NY Times), and if the author is trying to say this sets Neanderthals apart from "modern" Homo sapiens, that is way off base. Clearly there needs to be more analysis of the archaeological context of this site before we understand what the (alleged) cannibalism was aboutâwhether it was starvation cannibalism as suggested above, or culturally approvedâin the latter case, isn't it often part of funerary ritual?

While you're talking about "Neanderthal-like behavior," kindly remember that they were the apparent victims of direct or indirect genocide by H. sapiens sapiens, not vice versa.

In my review of the paper published in PNAS (see: http://www.pnas.org/content/early/2010/12/14/1011553108.abstract), this study represents the largest Neanderthal group for which reliable DNA sequence could be obtained, allowing the scientists to determine how the individuals were related. I agree that there is much more research to be done and that some of the reporter's terms were used for stylistic and not scientific purposes. The DNA evidence is consistent with three adult females belonging to different lineages, and three adult males belonging to the same lineage - Neanderthals could have exchanged females from different groups.

According to the paper, "all types of skeletal remains show evidence of anthropic activities associated to cannibalism..."

What distinguishes this study from others is that it draws upon extensive DNA evidence taken directly from skeletal samples dated some 50,000 years ago.

Thanks for the link to the audio interview. Indeed, neanderthal cannabis would be a very different topic - a new twist on the medical use of marijuana??

Would the actual facts please stand up? I keep reading that our DNA is partly Neandertal, and then that it definately isn't! It's as if geneticists have succumbed to CNN disease - Totally messed up and confusing info presented as "NEWS" - yikes!

That is a perception issue, I believe. The data from the Paabo group in Germany was incontrovertible - I cite their studies towards the end of my article with some very informative links from the journal Science.

oh, tell the truth! you know these folks were just trapped while trying to cross Donner Pass, or were just trying to survive after an airplane crash!

Big deal! Cannibalism has always been present in some human societies. Just look at some findings from old Anazasi sites. As for starvation cannibalism, it is with us even today, as distinct from culturally approved cannibalism. And what about nazis who make lamp shades from human skins? That was not long ago...

I liked the photo of the neanderthal mock-up. It looked like photos I'd seen of Charles Bukowski.

This genome discovery about our link to the Neanderthals has finally put to bed something I sensed all along but just couldn't nail down. But finally, there it is: the roots of the outlandish, brutish, selfish behavior of so many in the Republican Party. Yes, the unexplainable, detestible actions of some of our fellow humans is undoubtedly the result of them being direct decendents from some cannibalistic branch of the Neanderthal family tree.

For some reason, I thought it was the other way around... that there was more evidence of butchering and eating of humans among the early H. sap. sapiens.

As for modern humans—Sawney Bean, anyone?

It is highly unlikely that anyone but other Neanderthal's
committed the cannibalism.As the original article points out, the blades in the cave used to cut flesh were only Neanderthal technology- there was quite a bit of difference
between H. sapiens and H. neanderthalis in blade technoogy.

Please note one punctuation error: In American English, periods and commas go inside the quotation marks as in "food for thought," like so.

Thank you for catching this!

As expressed, at least in part, by several other comments here, despite arguments about 'style of blades' which is based I'd suspect on minimal evidence - I'm much more willing to go with the 'theory' that this cannibalism was the work of H. sapiens, and could even be considered as at least partial cause of the disappearance of H. neanderthalis

Taste like chicken ? NOT!!!...more like Pork , so i'm told !
.....Explains volumes about Cheeney and GOP'ers.....

I'm still not sure how this conclusively shows that Neaderthals were the butchers, although it sounds like they were definitely the meal. Maybe the culprit borrowed someone else's Ginsu?

There is some really interesting stuff on the Science website about the Neaderthals, and a very silly app on the Smithsonian site to see how you might have looked as a Neanderthal - see http://www.genome-engineering.com/sequencing-the-neanderthal-genome-the… for links

The evidence of cut marks and broken bones suggesting the marrow was sucked out is compelling in terms of indirect evidence, however, the lack of direct evidence such as coprolite containing human remains proving human flesh was digested leaves me skeptical that this was in fact an act of cannibalism. Many other explanations are viable. This may include ritualistic mutilation, warfare, witchcraft etc. I realize that these explanations may defy Occam's razor and climb higher on the ladder of inference, but these should at least be discussed and considered. Even if this is an example of cannibalism, we must not fall into the trap of negative evidence and believe that the only possible scenario is that a rival tribe of neanderthals cannibalized their own species over a territorial dispute. In other words, the evidence given leaves the hypothesis unproven and wide open for discussion. So lets discuss it.

This is my favorite blog in this section :)

Neanderthals were different biological species, though close to modern man - fact that can be considered proven conclusively.
The ancient people of all kinds were cannibals, were especially fond eating aliens.

Your genetic info -- not free, easy, or clear

ddobbs — Thu, 01 Apr 2010 09:03:53 +0000

Your genetic info -- not free, easy, or clear

After I wrote in my Atlantic article about getting my serotonin transporter gene assayed (which revealed that I carry that gene's apparently more plastic short-short form), I started getting a lot of email â several a week â from readers asking how to have their SERT gene tested. This led to an interesting hunt.

It was a hard question to answer. I couldn't just tell people to do what I did, for a psychiatric researcher/MD I'd known for years, who specializes in depression and serotonin, had done mine as a sort of favor to science and journalism. That researcher also stood by, had I needed it, to offer counseling and more information about the result's implications â an important point.

Obviously I couldn't pass that researcher's name out to several dozen strangers. Yet the readers who wrote wanted the information for the same reason I did: They wanted to know whether they had a genetic variant that by the conventional reading simply increased your risk of depression, but by another reading â the hypothesis explored in my article â conferred a broader sensitivity to experience, which can be a good thing.

As I well knew, this is powerful information. It opens a big box with lots of compartments. Those compartments hold things like the recently raised (but far from settled) question of how solid a connection the S/S variant holds to depression. They hold the question of how a person might interpret the results, and whether they have the emotional, intellectual, and social assets to make the most of the information; as well as the whole pile of broader issues raised by the growing availability of spitomics.

Challenging territory. Yet in this case the biggest challenge my serotonin-curious readers encountered was just getting the test in the first place. For try as we might, we could not find a place to run a SERT assay. People would try various companies, such as 23andme, and report back that they'd struck out. I suspect this is because the lawyers at such companies likely advise against giving test results regarding mental illness to people whose very interest in the test suggested they might be prone to depression.

So I started suggesting the long route to my solution: Try to find a psychiatrist at a research university interested in serotonin and convince that person, with your doctor's help if need be, to run the assay. That too proved elusive.

But one particular reader (I'll call her Natalie, which is not her real name) refused to give up. She wrote me back in early February saying her therapist had given her the Atlantic article, and she wanted to know her SERT type. She suspected she was indeed S/S. So off she went a-hunting. She struck out with the major gene-testing services, but after several back-and-forths and dead ends, seemed very close to getting an assay done at a nearby research university. The psychiatrist there, having read the article, seemed game, and set up an appointment. When she visited him, medical history in hand, the psychiatrist "was conscientious, thorough, and very interested, but understandably cautious." She liked him. But he ultimately declined to prescribe the test. He told her, she wrote me, that

the general body of research was inconclusive and contradictory, [and] professional organizations (such as AMA for geneticists) advised against it. Presently doing the test "would do more harm than good" and I should check back every few years when perhaps the test would provide concrete information. I think he was highly ethical and also covering his ass.

I think she's right. It's easy to understand this doctor's response. Some have lately questioned whether the S/S confers risk. Even if you believe the S/S does confer risk (and the field is very much split on this), do you want to deliver that news to someone whose depression might lead them to take the news badly? The view of S/S as a 'risk' gene rather than a plasticity gene remains the prevailing paradigm. And it seemed to drive the no-test decision Natalie and other readers encountered âeven though, in Natalie's case, she had shown the researcher the article and told him she was viewing the potential results as a sign of sensitivity rather than just risk.

But just at this point, where the road seemed to peter out completely, Karen found, hidden in the weeds, a lab that would run the SERT assay. Why would they do it?. Because, they said, "Researchers have found that mutations in some genes specifically change how effectively SSRIs may act," and that in the SERT gene, "[p]patients who have the short allele are less likely to respond to SSRIs or may take longer to respond."

This is true â but only in some trials, but not in others. The data on the SERT gene's effect on SSRI response is mixed. Yet it's interesting that the company lean on this to offer the test.

No matter to Natalie. She's primed to see what she's got. "I can tell you right now I am hoping for the short-short," she says. "The process is in the works for me, so now we shall see. This is so much fun."

I obviously think people should be able to get this information â though they should get it with some informed counseling. But this entire hunt, and the various reasons to give or not give people this information about themselves, raises a mess of intriguing and often slippery issues. The genetic testing industry, and the understandable excitement about the potential and power of genomic information, generally assumes that we either don't know a gene's meaning or that we do. But the case of the SERT gene shows that a gene's meaning can be far from certain -- and that it can change substantially as researchers do more work on it and view the existing data from different angles. Here we have a gene variant â possibly the most prominent in behavioral science, certainly in psychiatry â that, depending on whom you ask, is bad news, no news, or news whose meaning ... depends.

As the genome's parts come into view, their meaning sometimes shift. How will the fast-spreading, fast-growing gene-information industry handle this movement? How do you give people advice about a gene whose meaning seems to be changing? How, say, would a pre-conception gene counseling service, something along the lines of Counsyl, handle this dilemma?

This isn't something we'll figure out in a few blog posts; it's something the industry and the broader genomics community will need to consider carefully over the next few years, even as it rapidly grows. I'll be talking about and leading discussions on these questions at the upcoming GET conference in Cambridge and then at a closed workshop at the Institute for the Future â a start. Your own ideas â as well as pointers to other explorations of these questions â are most welcome in the comments or via the Twittersphere.

ddobbs Thu, 04/01/2010 - 05:03

"Your genetic info -- not free, easy, or clear."

And not useful, either.

They know the gene for Rett syndrome. Anything useful come of that yet?

They know the gene for Huntington's disease. Got a cure yet?

They know the gene for the familial form of ALS a/k/a Lou Gehrig's disease. Even though the familial form is only around 10% or so - nothing useful there either.

And so it goes.

They find "the gene for" whatever it may, but it does absolutely no good. They have, as the British like to say, the wrong end of the stick. Disgusting.

I disagree with this drama. I am old enough to remember when we didn't have the tech to know the sex of an unborn child. And then we did and then we had the same kind of discussion you and others like to engage in. As hard as it is to believe, people thought it would be "hard to handle" and they would need counseling. Scenarios were given such as, "Suppose this is the 4th child and all are girls and dad wants a boy. He might leave. Mom will get depressed and abandon the kids." It is the same kind of paternalistic, only we of the intelligentsia can handle this theme. Then one day everyone knew the sex of the unborn and the world went on spinning and dads didn't leave and moms didn't get depressed and run away.

It really isn't hard to explain: 1. This is not a given. 2. You control the eventual outcome because genes and environment are both important. 3. The only information this gives you is a roadmap for what actions you might take, what food you might eat, or how many music lessons you need to develop perfect pitch. 4. New information is being learned every day and this result could be overturned. 5. Check the following website for updates.

And yes - this info is useful. Even for HD or breast cancer. Suppose there was an alternative to the inevitable? There is in many cases. I'm taking low dose naltrexone not only for the chronic immune illness I have (and which is has stopped completely) but also because there is evidence it acts prophylactically on cancer. And it is being looked at for HD since it has been hugely successful in MS. (This isn't junk science. Clinical trials at Stanford, NIH, Penn State will show that.)

I'd say those who diss this and say, "no use" are pessimists who aren't thinking or curious and live in the past. Science moves forward by pushing boundaries. Don't shove it into the box labeled,"You need counseling." That's not helpful. And if you can't embrace and see the future without the sky falling in, find a way to prop it up instead.

I believe in the people and their power to learn. But they won't learn if they are told they can't be taught by those that clasp the knowledge close and will not teach or share.

Shamans see the coiled snake all the time and teach the tribes what life lessons it gives them. We call it DNA. It has much to teach and we have much to learn but we can't be afraid of its power and put it on a pedestal and keep it from the people.

Sit vis vobiscum

Why should people not be able to find out their genetic make up if they wish? Failure to allow open access to information moves science into the realm of religion and creates more problems than it solves.

Interesting articles you have very informative though for nobrains it seem hard to understand ! though i already read your articles over and over lol! maybe its not me ;) but you have interesting articles !

I find this very intriguing, thank you for the article, David. I have felt for years that I was prone to depression simply because both of my parents have had it. To know that there might be a gene out there that can prove just that boggles my mind. I would love to be tested for the S/S, but I doubt that insurance would cover it and I don't have the money to pay for it. While I understand that there are many facilities that won't do the procedure, do you suppose that there might be one that does? Where did Karen go?

What is the difference between the human genome and a pair of headphones?

edyong — Mon, 12 Oct 2009 06:30:16 +0000

What is the difference between the human genome and a pair of headphones?

If you've ever put a pair of headphones in your pocket, you'll know how difficult it is to keep a long cord in a bundle without getting it hopelessly tangled and knotted. You'll also start to appreciate the monumental challenge that our cells face when packaging our DNA. At 2 metres in length, the human genome is longer than the average human but it needs to be packaged inside the nucleus of every one of our cells, each just 6 millionths of a metre long. How does it do it?

One of the secrets behind this monumental feat of folding has just been revealed by research that reveal's the human genome's three-dimensional structure. A team of scientists led by Erez Lieberman-Aiden and Nynke van Berkum showed that chromosomes that make up our genome fold into a shape called a "fractal globule", where the long strands of DNA are densely packed but without a single knot. It's an awe-inspiring feat of space-saving and keeps DNA accessible. When a particular gene is needed, the DNA it sits on can be easily unpacked

Lieberman explains, "The best way to think about it is that it looks like a pack of ramen noodles when you just start cooking them: really dense, but totally unentangled, so you can pull out a noodle or a bunch of noodles without disrupting the rest." Previously, scientists suggested that the genome folds into a more tangled structure called the "equilibrium globule", which is more like ramen noodles post-cooking - a massive knotted mess from which single noodles are difficult to extract.

Until now, the fractal globule was a theoretical shape, and this is the first time that it has been observed in reality. The shape was first described by a mathematician Guiseppe Peano in 1890 and in 1988, Alexander Grosberg proposed that a long molecule might spontaneously fold into such a shape under the right conditions. Still, it took till this week for anyone to observe a fractal globule in reality. "[Peano] had no idea that it described any actual object in the universe," says Lieberman-Aiden, "but it turns out it describes the genome!"

Some of the other tricks that cells use to fold the genome are well documented. At the most basic level, DNA is wrapped around proteins called histones, like a series of beads on a string. These are then twisted around each other to form a wider filament, like the individual strands of a piece of rope. Beyond that, things become less clear but this new study shows what happens at these higher levels.

Imagine a series of beads on a string. You gather clumps of beads and crumple them together into a globule, carefully avoiding any knots or crossovers. Every row of, say, five beads gets crumpled into a globule, every row of five globules gets crumpled together, and so on and so forth. The final result is a single ball - a "globule-of-globules-of-globules".

Lieberman-Aiden developed a technique called Hi-C that simultaneously analyses adjacent DNA across the entire genome, in order to reveal its 3-D shape. It relies on formaldehyde to immobilise pieces of DNA that sit next to each other, effectively freezing the genome and forming cross-links between adjacent strands. The DNA is then shredded and the cross-linked fragments are isolated, sequenced and mapped onto the reference copy of the human genome. The result is a library of all the DNA strands that were neighbours in the nucleus, which can be analysed with computers to understand how the genome must be folded.

The technique confirmed that parts of the genome that would sit far apart if it was fully stretched out are actually very close to each other in space. Because of the complicated molecular origami that goes on inside the nucleus, around three quarters of the close-contact sequences identified by the Hi-C method are actually distant ones.

As an example, Lieberman-Aiden use glow-in-the-dark molecules to tag four stretches of DNA called L1, L2, L3 and L4. They lie one after the other on chromosome 14, but in the nucleus, they pair up differently. L1 and L3 are typically found in the "ON" compartment and are always closer to each other than L2. Meanwhile, L2 and L4 are closer to each other than L3, and are usually found in OFF territory.

The research also confirmed that the nucleus is divided into two territories - an "ON" compartment where DNA is rich in genes, highly active and loosely packed, and an "OFF" compartment where DNA is gene-poor, largely inactive and densely packed for storage. Individual chromosomes snake in and out of these two compartments and when a given gene is activated, it moves from one to the other. It's not clear what defines the boundaries between these two compartments, but Lieberman-Aiden suspects that these boundaries are very sharp.

"A huge question in biology is how all the different cells in the body perform totally different functions when all of them have the same genome," says Lieberman-Aiden. "This work suggests that the spatial arrangement of the genome in a particular nucleus is a big part of why different cells do different things."

PS: The BBC have also covered this story, but in amusing fashion, they have illustrated it with the wrong globule. The picture on their story is the equilibrium globule, not the fractal one!

PPS: You may remember Erez from the irregular verbs paper that I recently reposted. Many thanks to Erez for the heads-up about the paper and the awesome ramen noodle analogy.

Reference: Science 10.1126/science.1181369

More on genomes:

edyong Mon, 10/12/2009 - 02:30

Tags

Interesting! Question: The technique confirmed that parts of the genome that would sit far apart if it was fully stretched out are actually very close to each other in space.

Is this determined by the DNA itself somehow, or is it semi-random? In other words, if two sections are adjacent in one cell, are they adjacent in all cells of the same type? And in relatives? I'm just wondering, if this is the case, could that play an as-of-yet unrecognized role in genetics?

Christina -- see the work of Wendy Bickmore and related groups, who have suggested that chromosomal translocations between completely different chromosomes happens more often between regions of these chromosomes that co-occur in 3-D space more frequently.

Is there anything Ramen noodles can't teach us?

Christina, the compressed but knot-free structure of DNA strand can not be semi-random, as e.g. the Hamilton and Peano fractal curves arise as a result of an intrinsic recursive algorithm (see Wiki for as much detail as you care to immerse yourself). The beauty of this result is, that the long-suspected fractality of DNA (e.g. the Hamilton concept first advocated by Alexander Grosberg two decades ago in Moscow and later in New York University) will leave little doubt, just as you say, that fractal structure results in fractal function - e.g. as FractoGene conceived from fractal model of brain cell, assuming recursive iteration to DNA in 1989, unfolding in The Principle of Recursive Genome Function by 2008.

Music, food and dna. some of my favorite things. cool analogy.

Hi Ed, the comment about the BBC article, it made me go to their site and have a look and it was as you said ;)
I put a feedback there with a reference to your blog (as I am no expert on this) and now it's the right picture there...

I donno if it was the feedback or if they found it by some other means.. anyways.. thanks for such an intereseting blog.. I just happened to stumble upon it and LOVED it :)

http://www.codefun.com/Genetic_max.htm

Why don't we finish the human genome first?

sporte — Fri, 08 May 2009 06:00:18 +0000

Why don't we finish the human genome first?

One of the interesting things I learned today was that many people are calling for the genome sequences of the chimps and Macaques to be finished.

This is especially amusing because the human genome isn't quite done. We're primates, too! Why not finish our genome?

[I blame these new-found revelations on Twitter. Despite my youngest daughter's warning that only old people use Twitter, I've joined my SciBlings and taken the plunge. (you can even follow me! @digitalbio).

Now, I get to indulge my geeky tendencies while waiting in line at the grocery store. I just type #cshl and voila! I get the low down on the best and boringest talks at the Cold Spring Harbor genome meeting.]

What do you mean the human genome isn't done!

Yes, I know there was a press conference a few years ago so people could congratulate themselves for having finished sequencing the human genome. And, I suppose the main characters were finished with sequencing the human genome.

But finished â complete and the word "done" is rather subjective. I know I define "done" differently sometimes than my children.

"Done" doesn't mean we know the entire sequence.

This image shows the parts that are done in blue and the parts that are not done in black. Presumably, medically unimportant genes (if any) map to those black, unfinished parts.

The page also has a funny note saying "Next Build Release Spring 2009" Is it Spring yet?

I know there were good reasons for doing the parts that got finished and leaving the other parts out of the definition of "done." But DNA sequencing has come along way from the days when people used to joke about sentencing errant post-docs to concentrated sequencing camps.

But if there's a commitment to finishing a primate sequence, can we get our genome done too?

sporte Fri, 05/08/2009 - 02:00

Tags

Hey Sandra,

Well... the non-human primate genomes could be substantially improved with a few lanes of Solexa, whereas the remaining human regions are virtually impenetrable to short-read sequencing.

So while finishing human is important, the benefit/cost ratio is probably higher for spending a little extra effort on the primate sequences right now.

Hi Daniel,

Wouldn't it be helpful though to have a reference human sequence for comparison? It seems like we should be able to do it now.

Did those regions just get ignored when Venter's genome was done?

Actually, I believe the latest build (37) was released just recently I believe (http://www.ncbi.nlm.nih.gov/mapview/stats/BuildStats.cgi?taxid=9606&bui…)

Hey Sandra,

Another complication with finishing any genome, is that there is no single reference genome that represents a complete species. Look at the MHC haplotypes for example... Who knows we might actually have to abandon the whole notion of a reference sequence as it is defined at the moment. Maybe we'll get >100 reference sequences or so, or maybe a virtual one that combines all possible sequence variants into one reference. That virtual human genome might then be >100Gb, but would only serve as a scaffold to attach "real" genomes to.
It'll be interesting to see what the future brings.

And I concur with Daniel (probably because I work on the great apes :-)

They weren't ignored, they simply couldn't be assembled: a fair chunk of those regions are almost as impenetrable for BAC/capillary sequencing. Most of those black segments are the extraordinarily repetitive heterochromatic regions around centromeres, or the even nastier segments on the Y chromosome.

But should we invest time putting together a complete human reference assembly? Absolutely - and not just spanning the repetitive regions, but also including all of the novel sequence found in some individuals but not others. There was some talk at the 1000 Genomes meeting earlier this week about this, and I think it will happen sooner rather than later.

Should we also encourage a sequencing centre to devote a couple of lanes of their spare sequencing capacity to increasing coverage of chimp/macaque/other primates? Given that one lane of Solexa now gives ~1X coverage for a primate genome, it would be criminal not to.

Hey Sandra,

You should learn, and write, about that 1000 human genomes project. It is an international project. Venter, of course, is involved.

You should also learn that there are a few "finished" human genomes already.

The difficulties for truly finishing the genome, as some explained above, well, are hard for now. So, no harm done if we insist on other primates to be sequenced. Since we are so similar, I doubt those genomes will get to a better "finish" than the human ones. But what the heck.

Best,
--Gabo

Oh, I was forgetting.

There is a recent article comparing a "human cancer genome" to other human genomes. Venter's and Watson's.

Best again,
--Gabo

(maybe science or nature)

Thanks Gabo,

I am interested in the 1000 genomes project, too.

For the past few months, I've been pretty focused, work-wise, on transcriptome analysis. That's why I would like to see a reference genome, or maybe several reference genomes get completed so we could use them for aligning Next Gen data.

Plus, I think human DNA would be easier to collect.

It is interesting- the reasons that have been given here as to why the human genome are not complete are exactly the reasons why we should do it! How else will we learn to deal with these issues?

At least they got rid of the vector sequence data that was assembled into the first few drafts!

Gabo:
There are no finished human genomes. The data being produced in the 1000 genomes is largely of the short-read variety and will be used to align to the public reference assembly to identify differences, but the data will not be assembled as such. This is true of all of the genome sequences that have been reported, save the Venter genome.

Sandra:
Sorry it took a while to get the GRC pages updated, we had some technical difficulties, but they are updated now. We are trying to use data from the Venter assembly, as well as other sources, in order to improve the reference. We even have a way to collect assembly problems from users!

The seeming contradiction in wanting to "finish" the genomes of chimp and macaque versus finishing the human is simply in the definition of the word "finish". We now have random shotgun sequencing for several different humans, with many more coming, in aggregate comprising fantastically deep coverage of the human genome. No other genome of comparable size has anything close to as complete coverage and analysis as the human genome. The few remaining gaps have not been closed because: (1) It is not simply a matter of sequencing, but instead is the resolution of vast tracts of repeated sequences. (2) The number and composition of these repeats is not very interesting scientifically and probably varies a lot among humans anyway. (3) The effort at understanding the variation among humans is much more interesting and important (see the fantastic work of Evan Eichler's group, for example) than obsessing about these gaps of trivial importance. In contrast, when people are talking of "finishing" the genomes of chimp and macaque and other organisms, they are speaking of further efforts at improving the quality of these draft genomes. No one even imagines that sufficient effort will be expended any time soon to get these anywhere close to the quality of the human genome sequence.

I may be wrong here but I was under the impression that there were several bits of the genome that, as yet, *couldn't* be finished. Very repetitive C/G sequences, or impossible spice sites and things.

Of course, teaching always lags behind research a bit, so I could be very wrong there. :)

Hi,
the black parts on the genone could not be done due to technological reasons. The blue parts are as good as it gets, so it's perfectly reasonable to consider our genome 'done': it simply couldn't have been done 'more'. The black parts are not doable (or rather: not doable with reasonable time, cost and effort using current techniques), for now.

You could always argue that the blue parts could be done better (improve error rate, assembly, annotation etc.), but this is in fact happening all the time, and subsequent builds of the genome are affected by this ongoing work.

There is no 'absolute' genome, because we still don't quite know how genome works etc. (imagine that a few years ago we didn't know about microRNAs). But in terms of raw sequence, it's done.

It seems that now the goal is to have complete (in the current reference genome sense) diploid genomes from as many individuals as possible. BTW: the reference genome we all know is not a diploid genome, and not a genome from any person, it's a composite from couple of individuals ;-) - as such it's not too good as a reference, but it's the best there is.

cheers
yot

Yot-
The black parts of the genome (in the picture above) are certainly more difficult, but work is being done to obtain sequence information for these regions. See http://genomereference.org for more information.
But- the idea is to make the reference even better, it currently represents some highly variant regions with 'alternate loc'. Producing these alternate loci allow us to make the reference assembly better- in fact, we show 8 different haplotypes at the MHC locus (the representation in the reference chromosome + 7 alternate loci) so GRCh37 can represent more diversity than a diploid assembly at a given locus.

just thought u would be interested with these gap closing strategy
the authors bypassed the cloning step

Thanks noyk,

I just finished reading the paper. yeah!

Hi, I agree with the above entry. Greetings thread author. Waiting for the next entries.