Complete Genomes of All Known Human Rhinoviruses are Published; Rhinoviruses Are Associated With Common Cold

A team of researchers from the J. Craig Venter Institute (JCVI); the University of Maryland School of Medicine and the University of Wisconsin, Madison; announced today they have sequenced and analyzed the genomes of all known human rhinoviruses (HRVs). The whose work was published in Science Express, the online edition of the journal Science.

Rhinoviruses, part of the Picornaviridae family, are immediately familiar as the cause of the common cold, but they are also responsible for acute lower respiratory symptoms, and are a major cause of emergency room visits for patients suffering from asthma and chronic obstructive pulmonary disease (COPD). The direct and indirect cost of treating these illnesses is billions of dollars yearly, thus finding new ways to treat and perhaps prevent these illnesses could substantially cut health care costs.

Rhinoviruses are traditionally divided into two groups, HRV-A and HRV-B, consisting of 99 viral serotypes. The extraordinary genetic diversity of circulating rhinovirus serotypes has prevented the production of a universal vaccine for the common cold. A recently discovered third group of rhinoviruses, HRV-C, has swept the globe causing severe lower respiratory symptoms in patients.

To better understand the biology, diversity and evolution of human rhinoviruses, the researchers in this study sequenced and analyzed the genomes of all known HRV-A and B reference strains, as well as 10 new field isolates. The whole genome sequencing and bioinformatic analyses on the rhinovirus evolution were conducted at JCVI.

By constructing a rigorous phylogeny of all complete HRV genomes, the team gained new insight into rhinovirus evolution. They clearly showed that HRV-A and HRV-C evolved from a common ancestor and that HRV-B is "sister" group to the other two species. Interestingly, the team also uncovered within the HRV-A strain what they believe could be a separate, distinct fourth HRV subgroup.

The authors demonstrated in this study that recombination, the exchange of genetic information by breaking and rejoining nucleic acid sequences, is a common evolutionary mechanism in rhinoviruses. Co-infection with multiple viruses in individual patients can lead to the generation of novel rhinovirus serotypes. The authors also saw a high rate of diversity among field samples of the same HRV serotypes in the same geographic area over a short time period, suggesting that rhinoviruses may escape antiviral drugs through rapid mutation.

The researchers also found several areas of interest in the HRV genomes which could help to better understand the infection mechanism. Specifically, nearly all the HRVs displayed a hypervariable region in the 5'UTR. In the poliovirus a similar region is found which determines the virulence of that virus, suggesting that this genomic region could determine the pathogenicity of individual HRV strains.

According to researchers this study provides the scientific community with an extremely valuable resource for studying viral evolution. One researcher on the team says, "It is a very exciting time in viral genomics. Next generation sequencing technology will allow researchers to study as never before the evolution of viral populations worldwide. The completion of the HRV reference data set will open the door to mass comparative studies of rhinovirus evolution and global migration patterns."

Further full genome analysis with potentially thousands of additional field strains should enable even better understanding of these viruses leading to improved antivirals and vaccines.

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Advance in DNA Sequencing Announced

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Feds Fund Research on 'Economically Important Plants'

Scientists will find improved ways of studying the structure, function and evolution of the genomes of economically important plants, thanks to $14 million in new awards from the U.S. National Science Foundation (NSF).

Resources to be developed include genomic sequences, genetic markers, maps and expressed sequence collections. These are much-needed tools for researchers working in areas as diverse as genome evolution and plant breeding.

Awardees will address scientific questions including the role of polyploidy in genome evolution, the genomic basis of speciation, and the relationships between cultivated plants and their weedy relatives.

"If the Plant Genome Research Program has been making the bricks that build a conceptual framework for the genomes of economically important crop plants, these projects will provide the mortar," says James Collins, NSF assistant director for biological sciences. "The impact of genomics in evolutionary, ecological and population studies of crop plants will be far-reaching."

Many crop plants have large, complex genomes that in some cases are "polyploid" -- containing multiple genomes. Polyploidy is widespread in plants and animals, and can lead to dramatic changes in gene content and genome organization that are only just beginning to be understood.
A project led by researchers at Iowa State University will develop sequence and map resources to study polyploidy in cotton, while researchers at the University of Missouri will look at the impact of polyploidy on plant form in Brassica species, which includes plants such as canola and Brussels sprouts. Other projects at the University of Georgia and the University of Arizona will develop sequence resources to study genome organization in wheat and rice.

The outcomes from these projects will allow researchers to understand how extra copies of genes function in these plants, and how genomes from different sources can work together in a single plant.

The ever-growing collection of genome sequences is shedding light on the variation between individuals within a species. For example, in a forest of trees or a field of corn, there may be many versions of a particular gene, each with minor sequence differences. These sequence differences can sometimes have dramatic effects on growth and development.

Projects based at the University of California at Davis and Cornell University will catalog variants in pine trees and in maize, respectively, to allow researchers to link genetic variation with changes in gene function. This information could have applications in plant breeding.
More than half of the world's most cultivated crops have relatives that are invasive weeds, competing with the crop for nutrients and water and leading to reduced yields.

One example is red rice, a weedy form of rice that reduces the yields of cultivated rice by as much as 80 percent and contaminating harvests with its small red-coated grains. A project led by researchers at Washington University St. Louis will examine the regions of the red rice genome associated with weediness to find out whether it originated from the domesticated crop or if it was introduced as a weed from Asia.

A related project led by investigators at Michigan State University will investigate differences in gene expression in weedy and cultivated radishes to uncover which genes are associated with invasiveness.The outcomes of these projects could lead to a great understanding of how plants become weedy and invasive, and yield possible avenues for better selective control of weeds, scientists believe.

"The outcomes of this new program will tie together studies of the evolution of gene structure, function and regulation across the whole plant kingdom," says Collins.

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Newsweek: Genome Sequencing Begins To Payoff

Three years after scientists announced they had sequenced the human genome, new knowledge about how our genesaffect our health is transforming the way diseases are understood, diagnosed, treated-and even predicted, reports Newsweek senior writer Claudia Kalbin.

Newsweek's latest installment of its ongoing "Health for Life" series,"What's Next in Medicine" is in the December 11 issue, on newsstands Monday, December 4.

Today gene tests are available for more than 1,300 diseases, including cystic fibrosis and hemophilia. And now, as genetic screening gets cheaper and faster, researchers are hunting down the biological underpinnings of more-complex disorders that involve multiple genes-big,rampaging illnesses that strike millions of Americans every year. On the list: type 2 diabetes, Alzheimer's, heart disease and depression.

If the scientists are right, genetic tests for some of these diseases could beavailable by 2010. "We are on the leading edge of a genuine revolution,"says Dr. Francis Collins, head of the National Human Genome Research Institute.

The gene tests currently offered for certain diseases, like breast andcolon cancer, affect only a small percentage of total cases. But the impacton a single life can be huge. The key: being able to do something to ward off disease. "Genetic testing offers us profound insight," says Dr. Stephen Gruber, of the University of Michigan. "But it has to be balanced with ourability to care for these patients."

For example, the risk of breast and ovarian cancers in people with BRCA mutations can be reduced by frequent screening and radical surgery. Having healthy breasts or ovaries removed isn't easy, but the payoff--an end to constant anxiety and a pre-emptivestrike at disease--can be well worth it.

"Most women I've met who've had prophylactic surgery are glad they made the choice even if they're unhappy they were put in that position," says Sue Friedman, a breast-cancer survivor and head of FORCE, an advocacy and support group focused on hereditary cancers. "It's a double- edged sword."

The value of testing becomes especially murky -- and ethically complicated -- when there is no way to prevent or treat disease, as in the case of early-onset Alzheimer's, which often strikes before the age of 50,or Huntington's, Kalb reports.

Today, only about 5 percent of people whoare at risk for Huntington's, a devastating neurological disorder, take the test. Many are worried that genetic testing will put their health insurance or job security in jeopardy. Some people, however, can't live with uncertainty.

Stephanie Vogt knew Huntington's ran in her family -- her paternal grandfather and his three brothers all died from complications ofthe disease-and she wanted to find out where she stood. "As soon as I foundout there was a test, I just had to do it," she says.

In August 2000, after comprehensive genetic counseling, Stephanie, her sister, Victoria and their mother, Gayle Smith, learned her results: positive. "It was like a scene out of the Matrix, where everything freezes and starts again," says Stephanie.

On good days Stephanie feels empowered; on bad days she's frightened. "But most of the time," she says, "I'm comfortable with the fact that I have the knowledge."

Testing is just one piece of the genomic revolution. A major goal is to create new sophisticated therapies that home in on a disease's biological glitch, then fix the problem. Already, genes are helping to predict a patient's response to existing medications. A prime example in this field of pharmacogenetics, says Dr. Wylie Burke of the University of Washington, is a variant of the gene called TPMT, which can lead to life-threatening reactions to certain doses of chemotherapy. Knowing a patient's genotype,or genetic profile, may also help researchers uncover new preventative therapies for intractable diseases.

At Johns Hopkins University School of Medicine, Dr. Christopher Ross has tested several compounds shown to slow the progression of Huntington's in mice. Now he wants to test them in people who are positive for the Huntington's mutation but have not yetdeveloped symptoms--a novel approach to clinical drug trials, which almost always involve sick people seeking cures. "We're using genetics to move from treating the disease after it happens," he says, "to preventing the worst symptoms of the disease before it happens."

Scan of Human Genome Finds Unexpected Clues on Lou Gehrig's Disease

A comprehensive scan of the human genome has identified more than 50 genetic abnormalities in people with sporadic amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), the Muscular Dystrophy Association (MDA) and the Translational Genomics Research Institute (TGEN) have announced. The most common of these abnormalities have never before been shown to play a role in the disease.

TGen researchers, announcing the findings at an international ALS conference in Japan, said the identified differences implicate genes likely to play a role in cell function that controls nerve adhesion, offering a major new avenue for ALS research. TGen researchers identified the differences by screening DNA samples from over 1,200 people with and 2,000 people without sporadic ALS using state-of-the-art microarray technology by Affymetrix of Santa Clara, Calif.

"Our findings indicate these genes produce a sort of molecular glue that attaches motor neurons to muscle. It appears that in ALS the nerve is able to peel off the muscle and, when that happens repeatedly, the nerves die," says Dietrich Stephan, TGen director of Neurogenomics and the study's principal investigator.

ALS is a progressive neurological disorder that leads to paralysis and death in three to five years. It has baffled researchers for nearly 140 years.

What is extraordinary about this study is how quickly this breakthrough occurred. A new fast-track research funding approach used by MDA and a new microarray technology by Affymetrix that lets researchers quickly scan people's genomes enabled the experiment to be completed in just nine months.

"There is a revolution going on in research, and this study is a perfect example of how things are changing," says Sharon Hesterlee, MDA vice president of translational research. "New technology is letting us look at the genome at a level of detail that was unthinkable just a few years ago and, as a result, costs are coming down, results are coming much faster and we're seeing breakthroughs in diseases that have baffled researchers for decades."

The Affymetrix 500K Arrays identified the genetic differences between the affected and unaffected groups and rapidly produced a genetic map of each individual.

"Just a couple of years ago, this experiment would not have been possible because there simply wasn't a technology that enabled scientists to sift through the three billion molecules in the genome to find the genetic abnormalities that cause disease," says Sean George, vice president Academic Business Unit at Affymetrix. "The 500K microarray used on this experiment employs the same kind of semi-conductor technology that powers super computers."

According to MDA and TGen, the next steps center around high- throughput screening for drugs that act on the biochemical pathways identified by the DNA screen.

The massive project was funded by a $652,000 grant from MDA's Augie's Quest, a fast-track ALS research program, in collaboration with TGen. Blood donated for the study came from the MDA/ALS Center at Methodist Neurological Institute in Houston, the Forbes Norris MDA/ALS Center at California Pacific Medical Center in San Francisco, the MDA/ALS Center at the University of Pittsburgh, and the Eleanor and Lou Gehrig MDA/ALS Center at Columbia University in New York, as well as a dozen other collection sites throughout the United States.



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