Nature Newsblog
Jibril Hirbo hails from a tiny mountaintop town called Marsabit, in northern Kenya. Now, as a population geneticist, Hirbo has completed perhaps the largest-ever genetic study of people from Kenya and other East African nations.
Posted on behalf of Chris Gunter
Believe it or not, some people are complaining that now the ASHG meeting has too much genomics. This comes after years of dire warnings that the society was ignoring genomics at its own peril. Friday morning featured yet another all-genomics platform session, with multiple talks on sequencing whole human genomes.
Matthew Bainbridge of Baylor made crowd laugh by saying all we need is an assay with 100% sensitivity and 100% specificity. In the meantime, he’s using a method of sequencing a genome on two different platforms and comparing the results. He and others at the Baylor College of Medicine extended their work on personal genomes by sequencing in a family with a form of ataxia not due to a triplet repeat mutation, as many ataxias are. As in several talks at the meeting, Bainbridge and colleagues captured the sequence of the exome (or entire set of expressed genes) from key members of a pedigree, and by comparison of genetic variants were able to pinpoint the one gene they think carries the responsible mutation.
Continue reading "ASHG 2009: Sequence, and then sequence again" »
Posted on behalf of Chris Gunter
In 2006 I blogged from ASHG’s career development session and hate to say that not much has changed.
Back then I said “The session was kicked off by Bill Lindstaedt, Director of the UCSF Office of Career and Professional Development. He delivered the depressing news first: the median age of first tenure-track positions is 38; the median age of receiving a first NIH research grant R01 is 42; and only 4% of such grants go to first-time investigators.”
Continue reading "ASHG 2009: Your Individual Development Plan: Two Modest Proposals" »
Everyone wants to find the genes that "make us human." The problem is, when we find them, how will we know?
One of the major themes of this meeting is personalized medicine - the promise that some day, doctors will be able to tailor treatments for all of us based on our genetic makeup. Scientists and researchers are excited about the future prospects of personalized medicine, but there are also huge questions about how useful it will really be. Social scientists are wondering: can patients can handle genetic information? Will they overreact upon learning they have some small increase in risk for a disease? Or will the information wash over them like the myriad public service announcements exhorting us to eat right and get more exercise - messages that, apparently, most of us have learned to ignore?
Continue reading "ASHG 2009: Personal genomics fears overblown?" »
Nature reporter Erika Check Hayden (twittername @patsycat21) will be covering this year's American Society of Human Genetics meeting in Honolulu, Hawaii, from 20-24 October. Check back here for her coverage, as well as guest posts from Chris Gunter (@girlscientist), director of research affairs at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, and former Nature editor extraordinaire.
Albert LaSpada of the University of Washington in Seattle was able to reverse Huntington symptoms in a mouse model of the disease using a transgene expressing PGC1alpha. He presented details of his study on Wednesday, but gave a little additional background at a press conference this afternoon. It’s one of those lovely genetics discovery stories that not only offers promise for a devastating disease, but comes together so neatly when looked at in hindsight, I just had to relate it.
LaSpada was a grad student with Kenneth Fischbeck at the University of Pennsylvania in the late 1980s and early 1990s. Together, in 1991, they discovered the genetic underpinnings of X-linked spinal and bulbar muscular atrophy. It was caused by a gene with an abberant trinucleotide repeat. Two years later it was found that Huntington’s disease (HD) worked in much the same way, with an repeated CAG sequence in the huntingtin protein creating a long string of the amino acid glutamine. These repeats prevent huntingtin from folding properly and make it clump up in the brain -- a hallmark of many neurological diseases. The relatively high profile of HD made for a lot of excitement LaSpada says, and now there are at least nine of these so-called polyglutamine diseases known.
After he became a PI himslef, LaSpada had a trainee looking to treat HD who was going to test a cannabinoid drug in a mouse model for the disease. LaSpada predicted that the drug might interfere with temperature regulation, so he suggested that they observe temperature closely. They found surprisingly that untreated mice had very low body temperatures, leading them to speculate about the metabolic pathways that might have been contributing to this. In HD there’s the hallmark unfolded proteins, but there’s also dysregulation of transcription and mitochondrial dysfunction. But nothing linked the pathways together. Using the mouse model they were able to show how huntingtin aggregates interfered with the activity of PGC1alpha, a transcriptional co-activator involved in mitochondrial function in the brown fat by which mice maintain their body temperature. They engineered an HD model mouse to overexpress PGC1alpha and it both improved neurological function and cleared the huntingtin clumps. Screening for proteins that PGC1alpha interacts with reveals that it modulates the activity of PPARdelta. Another recent study LaSpada says, further shows that PPARdelta is involved in the response to retinoic acid, thus revealing two potential targets for drugs: ATRA, a chemotherapeutic that works like retinoic acid is already in use for promyelocytic leukemia, and GW 501516, a PPARdelta agonist has been used in clinical trials to modulate cholesterol and go after fat.
It seemed such a tidy path of discovery, definitely inspiring. Even the person following LaSpada at the press conference was a bit stunned. Before presenting his own results following humans with Gaucher disease, Hans Andersson at Tulane Univeristy in New Orleans just had to pause to say, "Cool. That's a cool story!"
I’ve got another fabulous guest post from Chris Gunter
At the Presidential Symposium, speakers pleaded the case for personal genomes and for Philadelphia. First was Philly mayor Michael Nutter, who assured us he knew absolutely nothing about genetics but joked that geneticists must have big expense accounts and the people of Philly would be very grateful if we could leave some of that money here with them.J. Craig Venter of the self-titled institute gave us a tour of his publication history and then of his own genome. (In an overlap with the carbon conference that Nature is also currently blogging, he announced that his J. Craig Venter Institute was building the first zero-carbon research building, on the UCSD campus.) As for his genes, he’s heterozygous in 44% of them, and he’s anxious to see this information translate into medical practice. “To me it’s not surprising that pharmaceuticals don’t work on everybody” because we are so different. In fact, “it’s amazing that they work on up to 1/3 of the population.” He reiterated his call for predictive power from the genome: “I have been arguing for some time that going to a preventative medicine paradigm is one of the few ways we have to lower health-care costs.”
Richard Gibbs of Baylor College of Medicine, the second speaker, picked up on the theme but stated that “we” –presumably meaning the genomics community – thought that there would be an orderly transition to genomic medicine, one would just walk into the doctor’s office and get genomic information and interpretation quickly. But we did not foresee the widespread distribution of direct-to-consumer tests, and the confusion that has resulted. We are driven by amazing advances in technology and therefore able to get mountains of genomic information, but we don’t really know what to do with it all. His personal experience, of course, is from sequencing Jim Watson’s genome. “We brought Watson to Houston for a genetic counselling session, which was pretty much a complete failure” because there were 320 loci with “suspicious” differences, based on the existing databases, and the counsellors were just overwhelmed.
Talk about overwhelming: In a plenary session on Wednesday David Kaufman of the Genetics & Public Policy Center told us that 60% of survey respondents would participate in genetic testing for a major medical research survey, and more than 90% of these said they would want to see their individual results (more on their survey here). So, it’s obvious the human geneticists have work to do in developing accurate but understandable interpretations of genetic tests. Any scientists out there who are not geneticists – please feel free to join the field, because we need you. All the better if you come with a big expense account.
Posted on behalf of Chris Gunter, HudsonAlpha Institute for Biotechnology
I couldn’t leave this be. I’ll be writing more about it soon, but these numbers are just staggering. David Altshuler gave a status report on the 1000 Genomes project, which aims to plumb the depths of human variation (I'm still waiting for the 1KG handle to take off). As it nears completion of its three pilot phase projects, it's generated 3.8 trillion bases of genome sequence. Although they haven’t yet sequenced 1,000 genomes, that is technically 1,000 human genomes worth of sequence data. Altshuler said that if you take the amount of data that was in GenBank at the start of the project, they put in roughly that amount more for each week of September and October. And they’re just a tenth of the way there! It’s useful to remember, Altshuler said, that the Large Hadron Collider, which is similarly expected to heave terabytes of data at researchers, had copious amounts of planning going into its data handling and analysis. 1KG will need to catch up quickly, hence two recent requests by the NIH looking for people with a plan and a heck of a lot of computational power. See here and here.
It's family history month, explained Ed McCabe of UCLA, president elect of the American Society of Human Genetics. This was at a press conference announcing the society's statement on ancestry testing, but he wasn't advertising for direct-to-consumer testing companies. Rather he suggested that this Thanksgiving, we should take the time to ask our elders about where we came from. Learning about the cultural richness of family history, he said, is very different from knowing that your genes say your are 40% european, for example.
I think family history month is largely recognized as October, but it's a nice sentiment, and I for one wish I had more people around to ask.
ASHG released recommendations today about how researchers and direct to consumer companies should treat the sometimes fraught area of genetic ancestry testing. Although a seemingly innocuous area both for research and for consumer products, ancestry testing does carry with it tricky ethical, legal and social issues when one considers how people might treat such data. I did a quick Q&A with Charmaine Royal of Duke University, who co-chaired the task force on the topic (find it here).
At the press briefing today, announcing the recommendations, I got to talk briefly with Joanna Mountain, senior director of research at 23andMe, one of the companies providing such tests.
She said the recommendations were provocative, but vague. Why, she asked, if they were going to make a big deal about how people might try to use ancestry tests to claim rights in affirmative action or for inclusion into specific groups, did they fail to provide any actual policy recommendations? Royal indicated to me that they’ve just begun to scratch the surface, here. Interestingly, Native American groups are keenly aware of the issues and will not allow identification with a particular tribe based simply on a genetic test, at least that’s what I’d heard at a session yesterday on the topic.
It is important to note that ASHG’s recommendations (you can find them here) were aimed both at academic researchers and those at direct to consumer companies. Mountain says, though, that 23andMe hadn’t been contacted and she suspects the task force hadn’t consulted with any of the companies. But as Royal said, there’s still a lot to be done including consulting with a broader swath of interested parties.
As a special treat, I’ve got a guest post from former genetics editor at Nature Chris Gunter. She’s also twittering the event here. How hip!
Aravinda Chakravarti’s presidential address was, of course, thoughtful and fun. He pointed out that it’s our responsibility to educate the public about genetics. I have been coming to the ASHG meeting since 1993, and have worked directly for two ASHG presidents and with many others. I believe every single presidential address I’ve seen since 1993 has made a similar call, for us to engage the community in education. In the age of direct-to-consumer genetic testing, we all know this is more important than ever. Unfortunately, this morning’s session on “the future face of genetics education” was sparsely attended, with only about 100 people. At the risk of repeating a cliché, all geneticists need to be educators, so I wish more people would take a more active interest in the area. It didn’t help that the ASHG scheduled six (SIX!) sessions at the same time and every one was interesting. The speakers discussed introducing genetics at all levels of education (full disclosure: two are colleagues from HudsonAlpha and one is a former colleague from NPG), and ways to measure what we need to teach and how we need to teach it. Many of the scientists attending the meeting will be teaching at some point in academia, or will be talking with their family and friends about genetics. Where were the scientists this morning? Similarly, the plenary session featured a talk on public attitudes toward genetic testing. People literally streamed out in droves right before this talk; they stayed for several research talks beforehand, but didn’t want to hear a data-driven study about how we should most effectively engage the public. This brings me to ask: are we serious about education, or not? Are scientists really uninterested in hearing about education, and how do they think they can afford to feel that way?Posted on behalf of Chris Gunter, HudsonAlpha Institute for Biotechnology
**Update: Link fixed. Sorry Chris!
Geneticists are taking an increasing interest in copy number variants (CNVs), genetic sequences that can be repeated or deleted from individual to individual. I might have two copies of a gene, while my wife might have three. These are a major source of genetic variation and have been implicated in contributing to important diseases. Alexandre Reymond of the University of Lausanne explained work he’s been involved with to characterize CNVs in mice. Looking at lab strains and several wild mice, they uncovered nearly 3000 of them. Then to understand how these CNVs might be affecting phenotype, they looked at gene expression in different tissue types in the mice to see if genes in and around those CNVs might be differentially expressed depending on how many copies there were. In five out of six tissue types they tested, as many as 2/3 of the CNVs they looked at were differentially expressed. The brain only showed 1/3 of CNVs affecting gene expression and generally doing so in a negative fashion. They found that genes far away from the actual CNVs could be affected, and one experiment suggested that the effects could span 10s of millions of basepairs, affecting the expression of quite distant genes. They also looked at expression during different developmental stages in the mice for brain and liver and found that while expression for 2/3 of genes in CNV regions were always affected in liver, brain CNVs appeared to be controlled differently at different developmental stages. Their findings had several people asking about how epigenetic changes like histone tail modifications might be influencing expression changes. I wonder how the brain specific differences square with discoveries linking CNVs to autism and schizophrenia in humans. Might there be a mechanism to protect the brain from CNVs that goes haywire for those affected?
Ancestry testing can be a sensitive subject as evident in a packed morning session discussing some of the social and education aspects of ancestry and genealogical testing. While genetics has a long and sordid past with the term race, it remains a fact (possibly as a vestige of how populations have been studied) that ethnic groups show distinct genetic signatures associate with commonly delineated ethnic groups, and there could be health benefits to using this information. Esteban Gonzalez Burchard at the University of California San Francisco studies African American and Latin American groups. He talked of one project on Multiple Sclerosis that he had been collaborating with. Multiple Sclerosis is predominantly a disease affecting people of European descent. Africans are rarely affected. So his group sent out requests for African Americans affected by the disease and used ancestry specific markers to zero in on portions of the individual’s genomes that might identify a European risk factor migrating through the genome. U.S. Television talk show host Montel Williams was a volunteer.
The series of talks ended with some rather passionate debate about the value of race as a term or even as a concept. While one questioner approaching the microphone at the end of the presentations pressed the panel and all in attendence to end its "love affair with the term." "Given that science has clearly shown that humans don’t meet the biological definition for race, why can’t science provide some leadership?" A genetic counselor was equally adamant that we don't avoid such terms just in the interest of being PC if they can provide useful health information.
Last night the American Society of Human Genetics meeting started in Philadelphia and kicked off with a crowded mixer featuring classic Philly fare (hoagies and pretzels). I asked Aravinda Chakravarti what he thought the major themes of the meeting would be. He said he was glad to report that the field has moved slightly away from data to new ideas. New ideas including better understanding of the genetic structure of disease and the characterization and understanding of the meaning of structure in the genome, including copy number variations (a term that appears in the abstract book more than 200 times). That’s not to say that data have taken a back seat. It’s no secret that the data are pouring out from new sequencing technologies. Illumina staged a brief press conference featuring the three papers appearing last week in Nature that presented four new full human genome sequences, those of an Asian individual, an African individual and one from a woman and from the cancer that she eventually died from.
Stay tuned for most posts from the field, and possibly some guest posts.
Last night, NIH director Elias Zerhouni warmed up the geneticists with a sure-fire crowd-pleaser: a joke about the mishaps of Vice-President Dick Cheney, who's in town for a Republican fund-raiser. Zerhouni apologized for the bad traffic yesterday, which was all tangled up due to Cheney's motorcade. Zerhouni said he'd asked Cheney to divert his motorcade away from the convention center. In reply, Cheney invited Zerhouni on a hunting trip. "But I said no - I have a prior commitment to the American Society of Human Genetics," Zerhouni said, adding after a small pause: "That was an act of self-preservation."
Even just walking to and from the convention center here in New Orleans, it's impossible to miss the fact that this city is still recovering from the mass disaster of Hurricane Katrina last year. Lots of businesses are empty or shut down. Workers are still clearing away rubble and there's small damage on some of the buildings. And this isn't even the part of town that was most affected by the storm.
Today, a handful of geneticists talked about their work to help the city recover. The geneticists were part of the team that tried to reunite families with their lost loved ones - whether dead in the storm or missing in its wake.
At least 250 postdocs and grad students attended a networking session here Tuesday night, in the ASHG’s new drive to provide content for younger members. The message was sobering: available academic positions are decreasing, and the number of PhD’s keeps increasing. What to do?
A quick sampling of three Fab Facts I learned today:
OK - so genetics hasn't delivered a slam dunk cure for fat. You still have to give up chocolate cake if you want to lose weight. As our interloper asked this morning, what gives? Where's the wonder drug that's going to save our sorry asses from dieting and exercising?
Sorry about the rocky start, folks - but I'm not the only one having trouble out of the starting gate! This morning, the geneticists got their own cold water in the face at a session on diabetes and obesity.
Hello all. Erika is having some troubles with computer connections but will be blogging madly starting today... stay tuned.
Nicola.
Here find our blog from the American Society of Human Genetics conference in New Orleans, where Erika Check will be sending back diary reports from 10-13 October.
You can also find the Nature homepage about this conference here.
