The-Scientist.com, October 8, 2009, by Jef Akst — Scientists have generated the most comprehensive map of the structural variation that exists among normal, healthy humans, according to a study published online today in Nature. Understanding normal variation between individuals is critical to identifying abnormal changes that may contribute to a wide variety of heritable diseases.
“I think it’s considered to be a landmark paper,” said geneticist Frank Speleman of the Center for Medical Genetics Ghent at Ghent University Hospital in Belgium, who was not involved in the work. “It’s quite important in the complete context of genome wide association studies and genetic predisposition.”
Using microarrays that contained more than 42 million probes, genome scientist Stephen Scherer of The Hospital for Sick Children in Toronto and the University of Toronto and his colleagues searched the genome of 40 healthy individuals for copy number variants (CNVs) — areas of the genome that come in varying quantities as a result of deletions, insertions, or duplications. The researchers identified 11,700 CNVs 443 base pairs or greater in size, with an average of approximately 1,000 CNVs differing between any two individuals. “[That’s] an important amount of normal variation that happens in the genome,” Speleman said.
The team then genotyped more than 5,000 of the CNVs from 450 individual genomes pulled from the International HapMap project to determine the population frequency and distribution of these variable regions. This generated a database of normal variation that can be correlated to specific populations and examined for patterns of inheritance among related individuals.
“There is this paradigm shift that CNVs are being incorporated into genetic studies,” Scherer said. “And I think it’s going to enlighten a lot of our interpretations” of genome wide association studies and other human genetics research.
Scherer and his colleagues generated a similar map in 2006 which, “while comprehensive,” Scherer said, “was pretty low resolution.” At that time, the researchers could only confidently detect CNVs of 50 kilobases or more. “We had no real idea of what the characteristics looked like,” Scherer said. “Some of the CNVs were in fact overlapping with other CNVs and we couldn’t really tell what was what.” Now, just three years later, they’ve upped their resolution by two orders of magnitude — a goal coauthor Matthew Hurles quoted to The Scientist after publishing the first map.
With this higher resolution technology, the researchers believe they have documented about 70% of the common CNVs (those that occur in more than 5% of the population). The CNVs they identified, however, failed to explain the high heritability of many complex diseases. The contributing factors, Scherer suggested, are likely to be the rare CNVs, which are more difficult to identify.
While the results of this study clearly fill in some important detail to the map of human CNVs, there are still many CNVs left to be discovered, the authors admit. “I’m excited by the fact that they’ve finally released this data,” said human geneticist Evan Eichler of the University of Washington. “[But] I think this is far from being comprehensive at this point.” The next step, he said, is sequencing individual genomes with long reading frames to further increase the resolution. “You’re only as good as you can genotype,” he said.
The study “tells us something about the frequency of CNVs and sheds a little bit of light on their role in common disease,” said molecular biologist George Zogopoulos of the University of Toronto, who also did not participate in the research. “[Now] we need to look at diseased genomes.” Comparing the genomes of individuals affected by certain diseases to healthy controls may identify important CNV-disease associations, he explained.
Despite all that remains to be done, this study — along with other ongoing efforts to further characterize the human genome — have added tremendously to our understanding of human genetics, Speleman said. “In the past years, an enormous leap has been taken. We’re looking at huge amounts of information, which are generating a lot of new views on the variability of the genome.”
Immunity from prior exposure may make H1N1’s return less severe, experts say
GoogleNews.com, October 8, 2009, by Steven Reinberg — New York, Philadelphia and other cities hit hard by H1N1 swine flu last spring aren’t seeing as much of it now, even though outbreaks are occurring in all 50 states.
The possible reason: Many people in these spring-outbreak epicenters have already gained some immunity to H1N1, and this “herd immunity” is keeping a wider fall outbreak at bay, experts say.
According to a report released Thursday by the New York Times, health officials in New York City, Boston and Philadelphia say they are seeing less swine flu now than they did during the initial outbreak.
“This is very much in keeping with what I am seeing here in New York,” noted one flu expert, Dr. Marc Siegel, an associate professor of medicine at New York University School of Medicine.
“Not only is there not a resurgence of flu in areas where there were previous large outbreaks, but there are probably very mild cases going around that are going under the radar, because people don’t even realize they are flu,” he said.
Siegel agreed that widespread immunity from the spring outbreak may have led to a different kind of autumn outbreak. That’s because many people exposed to the flu don’t get seriously ill, but they do build an immunity to it. “There’s a large percentage of patients who don’t get ill — we only focus on those who do,” Seigel said.
In New York City, health officials say that while 10 percent to 20 percent of the population fell ill with the H1N1 virus in the spring, up to 40 percent of New Yorkers may have been exposed to the flu. These people may have become immune to the disease and are thus preventing it from spreading now.
This high level of immunity may make a second wave of the H1N1 much less extensive, the experts said.
“We’re not seeing illness in the city right now,” Dr. Thomas A. Farley, New York City’s health commissioner during a flu conference last Friday led by Kathleen Sebelius, the health and human services secretary. “We’re seeing essentially no disease transmitted in the city. We had 750,000 to one million sick people last spring. We were the hardest-hit city then. So we have a lot of immune people right now,” the Times reported.
Only about 150 to 250 people a day have been going to emergency rooms in New York City complaining of flu-like symptoms. Attendance in the city’s public schools was 91 percent on Wednesday. Compare that to last spring, when 60 city schools closed and some 18 percent of students were absent, according to the Times.
Dr. Anita Barry, director of the infectious disease bureau of the Boston Public Health Commission, told the Times, that although 11 percent of teens in her city got swine flu in the spring, public schools and college health services have reported very little flu this fall.
In addition, Seattle, Connecticut and Utah — where there was also a lot of swine flu in the spring — are seeing less now, Donald R. Olson, research director for the International Society for Disease Surveillance, told the Times.
Another expert said this phenomenon isn’t unexpected.
“As a result of last spring’s outbreak in certain areas of the country, one may see a pattern of uneven geographic distribution of cases in the U.S. this fall, depending on what occurred in specific geographic areas last spring. There may be few cases in some areas and a significant number of cases in others,” said Dr. Pascal J. Imperato, dean of the School of Public Health at the State University of New York Downstate Medical Center.
“The majority of cases, as was the case last spring, will probably be in children and young adults and will be clinically mild in nature,” he added.
However, even in places where the swine flu appears to be less extensive than before, it is still important for people to get the H1N1 vaccine, Siegel said.
“This is even more of an argument for the vaccine,” Seigel contended. “If people are immune based on previous outbreaks, imagine how good we can do with vaccinating the country. It seems that immunity is playing a pretty big role in areas where it spread previously, and if we vaccinate people we will really ante up on that.”
GoogleNews.com, October 8, 2009 — In this publication, we’ve been writing for years about the promise of “personalized medicine,” or treatments that use genetic information to offer therapies to patients most likely to respond. U.S. providers have conducted scattered experiments in using this approach, but as far as we know they’ve been pilots.
Now, Scripps Health is staking a claim to being the first U.S. hospital system to integrate personalized medicine into its cardiac programs. Scripps says it’s started offering a test to stent patients to determine which ones might best benefit from anti-platelet therapy–and which ones might not.
The announcement appears to build on study results, publicized in the Journal of the American Medical Association, offering evidence that people with a certain gene mutation respond less to treatment with Plavix than those without the mutation. Right now, Plavix is the second most-prescribed drug in the U.S., and is given to one million patients a year after they go through coronary stent procedures.
Scripps, which is working with Quest Diagnostics, will screen for the mutation among patients at one of its hospitals scheduled for elective coronary angiography procedures. About 70 to 100 of the 250 patients who undergo angiography each month at Scripps Green Hospital will be offered the test. If the program seems effective, Scripps may expand testing to the entire chain
GoogleNews.com, Brigham and Women’s Hospital has immersed itself in the business of conducting personalized genetic research on treatments for cancer, brain and heart disease.
Working with GE Healthcare, clinicians from Brigham are using molecular imaging and radiopharmaceutical development tools to find personalized treatments for these conditions. The two expect to leverage PET scanning technology from GE to boost their efforts.
By getting involved in such research, Brigham is becoming part of a rapidly emerging trend. Though only a few practical applications exist to date, a new report by the Deloitte Center for Health Solutions  finds that personalized medicine could provide significant ROI for all of the key stakeholders in the U.S. healthcare system.