Pupils studying science subjects find it harder to achieve top grades.Durham University researchers analysed and compared data from nearly one million pupils sitting GCSE and A-level exams and reviewed 28 different studies of cross subject comparison conducted in the UK since 1970.
They found significant differences in the relative difficulty of exams in different subjects with the sciences among the hardest. On average, subjects like Physics, Chemistry and Biology at A-level are a whole grade harder than Drama, Sociology or Media Studies, and three-quarters of a grade harder than English, RE or Business Studies.
A student who chooses Media Studies instead of English Literature could expect to improve their result by half a grade. Choosing Psychology instead of Biology would typically result in over half a grade's advantage. Preferring History to Film Studies, however, would cost you well over a grade at A-level.
The study found that these differences were consistent across different methods of calculation and were remarkably stable over time.
The implications are that students may opt for subjects that are likely to yield higher grades since grades on A-level exams are an import metric used for admission to universities.
Researchers voice concerns that students will be more likely to choose to study 'easier' subjects and will not opt to study science subjects that are desperately needed by employers in the knowledge economy.They are calling for marking for 'harder' subjects to take account of their difficulty, perhaps introducing a 'scaling' system similar to that already used in Australia so that some subjects are acknowledged to be worth more than others.
The report was commissioned by the Institute of Physics and the Royal Society on behalf of SCORE (Science Community Representing Education). Lead author is Dr. Robert Coe, Deputy Director of Durham University's CEM Centre.
See also July 1 report in Science Daily.
The Institute of Physics responds to the report's findings here.
]]>He suggests that this issue represents a cultural divide as much as a regulatory one.
The assumption that there must be a layer of "professional help" is exactly what the new age of medicine bodes -- the automation of expertise, the liberation of knowledge and the democratization of the tools to interpret and put to use fundamental information about who we are as people. Not as patients, but as individuals. This is not a dark art, province of the select few, as many physicians would have it. This is data. This is who I am. Frankly, it's insulting and a curtailment of my rights to put a gatekeeper between me and my DNA.]]>This is *my* data, not a doctor's. Please, send in your regulators when a doctor needs to cut me open, or even draw my blood. Regulation should protect me from bodily harm and injury, not from information that's mine to begin with.
Feinberg, a professor of molecular biology and genetics and director of the Epigenetics Center at the Johns Hopkins School of Medicine, added that they may also explain why diseases such as diabetes and cancer, in which we know the environment is important, might arise in part because the environment changes the genes themselves. “In this sense, epigenetics probably stands at the center of modern medicine because unlike our DNA sequences, which are the same in every cell, epigenetic changes can occur as a result of dietary and other environmental exposure,� he said.
“Abnormal methylation levels, either too much, which could turn necessary genes off, or too little, which could turn genes on at the wrong time or in the wrong cell, already have been shown to contribute to cancer and other diseases,� said Vilmundur Gudnason, M.D., Ph.D., a professor of cardiovascular genetics at the University of Iceland, who designed the Reykjavik, Iceland, component of the study.
For the new study, researchers first collected DNA samples collected in 1991 and again between 2002 and 2006 from 600 participants already enrolled in the AGES Reykjavik Study. The AGES study is renowned for its value to genetics research because of the historic isolation and reduced number of genetic “variables� among Iceland’s population, making certain patterns of genetic information easier to identify.
Among the 600, the research team measured the total amount of DNA methylation in each of 111 samples and compared total methylation from DNA collected in 2002 to 2005 to that person’s DNA collected in 1991.
They discovered that in almost one-third of the subjects, methylation changed over that 11-year span, with some gaining DNA methylation and others losing it.
“The key thing this part of the study told us is that levels changed over time, proof of principle that an individual’s epigenetic profile does change with age,� said M. Daniele Fallin, Ph.D., an associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health.
Still a puzzle, though, was why or how, Fallin said, “so we wondered whether the tendency to those changes was also inherited, right along with our DNA sequences. That would explain why certain families are more susceptible to certain diseases.�
To that end, the team measured total methylation changes in a different set of DNA samples collected from Utah residents of northern and western European descent. These DNA samples were collected over a 16-year span from 126 individuals from two- and three-generation families.
Similar to the Icelandic population, the Utah family members also showed varied methylation changes over time. But they found that family members tended to have the same kind of change: If one individual lost methylation over time, they saw similar loss in other family members.
“It seems,� said Fallin, an epidemiologist interested in patterns of disease among populations, “that epigenetic changes could be an important link between environment, aging and genetic risk for disease.�
Feinberg said interest in the field of epigenetics is growing because “the more we learn about the genetic contribution to aging, health and disease, the more we understand that the DNA sequences we inherit at conception are not the whole story.
“If it were the whole story,� he added, “then such things as susceptibility would not vary so much or change over time. We know that changes to the genome must occur but that nature protected that genome from easy alteration. Methylation is nature’s work-around.�
The research was funded by the National Institutes of Health, Swedish Cancer Foundation, Icelandic Parliament, Huntsman General Clinical Research Center, W. M. Keck Foundation, George S. and Delores Doré Eccles Foundation, Fulbright Foundation and the Icelandic Student Innovation Fund.
Authors on the paper are Hans Bjornsson, Martin Sigurdsson, Rafael Irizarry, Hengmi Cui, Wenqiang Yu, Michael Rongione, Fallin and Feinberg, all of Hopkins; Thor Aspelund, Gudny Eiriksdottir and Vilmundur Gudnason of Hjartavernd, Reykjavik, Iceland; Tomas Ekstrom of Karolinska Institute, Stockholm, Sweden; Tamara Harris and Lenore Launer of the National Institute on Aging, Bethesda, Md; Mark Leppert of University of Utah, Salt Lake City; and Carmen Sapienza of Temple University Medical School, Philadelphia, Pa.
Today, researchers from the University of Utah's Huntsman Cancer Institute publish data that support this hypothesis in the case of a genetic predisposition to malignant melanoma.
Science Daily reports today:
When people know the results of genetic tests confirming they have inherited an increased risk of developing melanoma, they follow skin cancer screening recommendations more proactively--much like those who have already been diagnosed with the potentially deadly disease, according to results of a study completed at the University of Utah's Huntsman Cancer Institute and published in the June issue of Cancer Epidemiology, Biomarkers & Prevention.]]> Tests for mutations in the CDKN2A gene can reveal a reason that melanomas "run" in families. The study evaluated the intent to follow, and the actual practice of, skin cancer early detection methods by members of families that carry CDKN2A gene mutations. Study participants were drawn from a group of Utahns who participated in the original "CDKN2A gene hunt" 10 to 12 years ago. They already knew that their family history might put them at increased risk for melanoma, and they had previously received melanoma prevention and screening education.
The results showed that people who tested positive for the CDKN2A mutation followed melanoma screening recommendations more carefully than before, even if they had not had a melanoma. In addition, knowing the test results did not lead family members without the mutation to decrease their screening measures.
"Before these studies, it was unclear whether reporting the results to family members who have been tested was valuable or potentially harmful to patients," said co-principal investigator Sancy Leachman, MD, PhD, director of the Tom C. Mathews Jr. Familial Melanoma Research Clinic (FMRC) and associate professor in the Department of Dermatology at the University of Utah School of Medicine. Leachman specializes in melanoma genetics.
Lisa Aspinwall, PhD, associate professor in the University of Utah Department of Psychology, is co-principal investigator on the studies. "We wanted to know whether learning their results helps people comply better with melanoma screening recommendations. We also wanted to know if people who find out that they are negative for the mutation decrease their efforts as a result of knowing their genetic status."
"People with a family history of melanoma who do not carry the mutation are still at almost twice the risk of developing melanoma as people in the general population," Leachman said.
Melanoma is the most serious type of skin cancer. The National Cancer Institute estimates that more than 62,000 people will be diagnosed with the disease in 2008, and more than 8,000 will die of it. Cancer experts estimate that about ten percent of melanomas are associated with familial or inherited syndromes.
Samantha Leaf, Erin Dola, and Wendy Kohlmann are co-authors of the published paper. The work was supported by a Funding Incentive Seed Grant from the University of Utah's Office of the Vice President for Research, Huntsman Cancer Foundation, the Tom C. Mathews Jr. Familial Melanoma Research Clinic endowment, the Pedigree and Population Resource of Huntsman Cancer Institute, and a Templeton Positive Psychology Prize, awarded to Aspinwall by the John Templeton Foundation and the American Psychological Association. Huntsman Cancer Institute core facilities are supported by a Cancer Center Support Grant from the National Cancer Institute.
]]>From a report today in Science Daily:
Dogs originally derived from the wolf more than 15,000 years ago -- a blink of the eye in evolutionary terms. Selective breeding produced dogs with physical and behavioral traits that were well suited to the needs or desires of their human owners, such as herding or hunting ability, coat color and body and skull shape and size. This resulted in the massive variance seen among the more than 350 distinct breeds that make up today's dog population. Until now, the genetic drivers of this diversity have intrigued scientists who have been trying to explain how and why the difference in physical and behavioral traits in dogs changed so rapidly from its wolf origins.An international team of researchers, which included scientists at the National Human Genome Research Institute, the University of Utah, Sundowners Kennels in Gilroy, California and Mars' Waltham Center for Pet Nutrition in the United Kingdom, studied simple genetic markers known as Single Nucleotide Polymorphisms, or SNPs, to find places in the dog genome that correlate with breed traits. Because many traits are "stereotyped" -- or fixed within breeds -- researchers can zero in on these "hot spots" to see what specific genes are in the area that might contribute to differences in traits.
The abstract and the paper can accessed here.
]]>In the June 19, 2008 issue of the New England Journal of Medicine, Kathy Hudson, MK Holohan and Francis Collins review GINA to succintly answer these in a short review that is freely available.
Although a landmark piece of legislation that provides much needed protection for healthy people with a genetic predisposition for disease, there are still gaps in protection. It is important for practitioners and researchers to understand GINA's strengths and weaknesses so that they can counsel their patients and research subjects with accurate and complete information about the risks and benefits of genomic medicine and/or participating in genomic research.
Below the fold is a bulleted summary from this article of what GINA addresses for practical purposes.
]]>Quick Guide to GINA]]>What GINA does
Prohibits group and individual health insurers from using a person's genetic information in determining eligibility or premiumsProhibits an insurer from requesting or requiring that a person undergo a genetic test
Prohibits employers from using a person's genetic information in making employment decisions such as hiring, firing, job assignments, or any other terms of employment
Prohibits employers from requesting, requiring, or purchasing genetic information about persons or their family members
Will be enforced by the Department of Health and Human Services, the Department of Labor, and the Department of Treasury, along with the Equal Opportunity Employment Commission; remedies for violations include corrective action and monetary penalties
What GINA does not do
Does not prevent health care providers from recommending genetic tests to their patientsDoes not mandate coverage for any particular test or treatment
Does not prohibit medical underwriting based on current health status
Does not cover life, disability, or long-term-care insurance
Does not apply to members of the military
Key terms
"Genetic information" includes information about:A person's genetic tests
Genetic tests of a person's family members (up to and including fourth-degree relatives)
Any manifestation of a disease or disorder in a family member
Participation of a person or family member in research that includes genetic testing, counseling, or education
"Genetic tests" refers to tests that assess genotypes, mutations, or chromosomal changes
Examples of protected tests are:
Tests for BRCA1/BRCA2 (breast cancer) or HNPCC (colon cancer) mutationsClassifications of genetic properties of an existing tumor to help determine therapy
Tests for Huntington's disease mutations
Carrier screening for disorders such as cystic fibrosis, sickle cell anemia, spinal muscular atrophy, and the fragile X syndrome
Routine tests such as complete blood counts, cholesterol tests, and liver-function tests are not protected under GINA
BETHESDA, Md. (June 18, 2008) A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy.]]> Environment can influence genesThe findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.
The study, “Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity,� appears in the online edition of the American Journal of Physiology-Endocrinology and Metabolism, published by The American Physiological Society.
The study was carried out by Linda Mustelin and Kirsi Pietiläinen, of Helsinki University Central Hospital and the University of Helsinki; Aila Rissanen, Anssi Sovijärvi and Päivi Piirilä of Helsinki University Central Hospital; Jussi Naukkarinen, Leena Peltonen and Jaakko Kaprio, University of Helsinki and National Public Health Institute; and Hannele Yki-Järvinen of Helsinki University Central Hospital and Minerva Medical Research Institute.
Recent studies have suggested that defects in expression of genes involved in the body’s conversion of food to energy, known as mitochondrial oxidative phosphorylation, can lead to insulin resistance. The researchers wanted to know if defects in the expression of these genes are primarily a result of heredity or lifestyle. Because the twins in the study were identical, any differences that were found could be attributed to environmental factors, the researchers reasoned.
Twenty four pairs of identical twins, born in Finland between 1975 and 1979, took part in the study. Fourteen pairs (eight male and six female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of five male and five female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.
The researchers measured whole body insulin sensitivity, body composition and cardiorespiratory fitness. They also obtained a needle biopsy of abdominal subcutaneous fat tissue, although they were unable to obtain this measurement for one of the discordant pairs.
Among the discordant pairs, the study found the obese twin had significantly lower:
* Insulin sensitivity, indicating the body has a harder time using glucose to produce energy.
* Fitness levels, as measured by maximum oxygen uptake and maximum work capacity.
* Transcription levels of genes that help cells convert food to energy (the genes of mitochondrial oxidative phosphorylation). Transcription is a multi-step process in which information in the genes is used to manufacture proteins. Proteins, in turn, direct cell activity. This suggests that the impaired expression of the genes may make it more difficult to lose excess weight, or may make additional weight gain more likely.
Heredity may still play role
“These data suggest that physical inactivity may have contributed to the defects in mitochondrial oxidative phosphorylation described in type 2 diabetic patients and prediabetic subjects,� the authors wrote. The authors also noted that, although environment plays a role in how these genes work, there still may be a hereditary component.
“Although we found that the reduced transcript levels of genes encoding mitochondrial oxidative phosphorylation in obesity is influenced by environmental and acquired factors, it does not exclude the possibility that genetic factors contribute to regulation of mitochondrial oxidative metabolism,� lead author Linda Mustelin noted.
The next step is to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.
From GenomeWeb News on June 16,2008:
By a GenomeWeb staff reporter]]>NEW YORK (GenomeWeb News) – The State of California is trying to keep consumer genetic testing companies from offering their services to the state’s residents and last week sent letters to thirteen firms saying they are violating state law, California Department of Health spokesperson Lea Brooks told GenomeWeb Daily News today.
The state will not disclose the names of the firms to which it has sent letters, or which laws their services violate, until the companies in question verify with the state that they have received the warnings, Brooks said.
With the move to begin regulating consumer genomics companies in the state, California follows New York State, which less than two months ago warned 23 companies that they must have permits to offer their services to New Yorkers.
New York’s warning letter was a shot across the bow not only to new companies, such as Navigenics and 23andMe, that last year entered into the fledgling field of consumer genomics, but also to technology suppliers Affymetrix and Illumina, which make the tools the testing companies use.
Whether California is focusing on consumer genomic testing companies or if it has broadened its authority to include technology suppliers will not be known until the authorities release the names of the companies it is contacting. California authorities also have not said whether information has been referred to the state’s Attorney General for further action.
One offense that genetic testing companies could commit would be to sell their products to California citizens over the internet without the request or counsel of a doctor, California Department of Public Health official Karen Nickel told Forbes.com last week. Another problem, Nickel said, could be that the companies’ tests have not been validated for accuracy or for clinical utility, which is required under California law.
Concerns over marketing genomic data to consumers and assertions about the ability of tests to predict disease risk were sharply rendered in January by Muin Khoury, director of the National Office of Public Health Genomics at the US Centers for Disease Control and Prevention.
After publishing a critical op-ed in the New England Journal of Medicine with two other authors, Khoury told GWDN that consumer genomics as it is today should be considered “recreational genomics,� and that the field was premature and consumers were not ready to receive the “alphabet soup� of genomic information they were buying.
To Khoury and his fellow NEJM writers, the problem of how to show the clinical usefulness of these genomics offerings would prove to be the most critical.
“The bottom line here is that people are beginning to be concerned that there may be more harm than benefit,� Khoury said.© Copyright 2008 GenomeWeb Daily News. All rights Reserved.
From a report today in Science Daily:
Lead author Dr Zita Martins, of the Department of Earth Science and Engineering at Imperial College London, says that the research may provide another piece of evidence explaining the evolution of early life. She says:“We believe early life may have adopted nucleobases from meteoritic fragments for use in genetic coding which enabled them to pass on their successful features to subsequent generations.�
Between 3.8 to 4.5 billion years ago large numbers of rocks similar to the Murchison meteorite rained down on Earth at the time when primitive life was forming. The heavy bombardment would have dropped large amounts of meteorite material to the surface on planets like Earth and Mars.
Co-author Professor Mark Sephton, also of Imperial’s Department of Earth Science and Engineering, believes this research is an important step in understanding how early life might have evolved. He added:
“Because meteorites represent left over materials from the formation of the solar system, the key components for life -- including nucleobases -- could be widespread in the cosmos. As more and more of life’s raw materials are discovered in objects from space, the possibility of life springing forth wherever the right chemistry is present becomes more likely.�
MARTINS et al. Extraterrestrial nucleobases in the Murchison meteorite. Earth and Planetary Science Letters, 2008; 270 (1-2): 130 DOI:10.1016/j.epsl.2008.03.026
Dr. Kathleen D. Griffith and colleagues authored a paper to be published in the July 15, 2008 issue of Cancer that suggests that African Americans with a family history of colorectal cancer get screened less than other groups with a family history of colorectal cancer. This finding suggests that there may be a need to identify the underlying reasons for this finding in order to address this gap in service provision.
Article: Influence of Family History and Preventive Health Behaviors on Colorectal Cancer Screening in African Americans. Kathleen A. Griffith, Deborah B. McGuire, Renee Royak-Schaler, Keith O. Plowden, and Eileen K. Steinberger. CANCER; Published Online: June 9, 2008 (DOI: 10.1002/cncr.23550); Print Issue Date: July 15, 2008. A free abstract of this article will be available via the CANCER News Room upon online publication.
A new study indicates that African Americans with a family history of colorectal cancer are less likely to be screened than African Americans at average risk for the disease.]]> To investigate the factors associated with risk-appropriate CRC screening, Kathleen Griffith, Ph.D., CRNP, of the Johns Hopkins University School of Nursing and colleagues at the University of Maryland Baltimore analyzed data from the 2002 Maryland Cancer Survey, a telephone survey of more than 5,000 Maryland residents, performed under the Maryland Cigarette Restitution Fund Program to identify predictors of screening among African Americans.There is also some evidence to indicate that African Americans with a family history are less likely to be screened than their white counterparts. The study is published in the July 15, 2008 issue of CANCER, a peer-reviewed journal of the American Cancer Society. African Americans have the highest colorectal cancer (CRC) incidence and death rates of all racial groups in the United States. The reason for this is thought to be multifactorial but remains poorly understood. Overall, African Americans have low rates of colorectal cancer screening compared to most other racial groups. Early detection is especially important for those with family histories of CRC who are at higher risk of developing the disease. Factors associated with CRC screening are not well understood for African Americans, both those with and without family histories of CRC.
The researchers analyses revealed that for African Americans, regardless of family history, a health care providers recommendation for colorectal cancer screening was strongly correlated with a higher likelihood of screening. Furthermore, individuals who were more physically active were also more likely to have been screened for colorectal cancer. Surprisingly, though, having a family history of colorectal cancer did not predict a higher likelihood of screening. In fact, the researchers found that African Americans with a family history were less likely to have received risk-appropriate screening than those without a family history. Family history of colorectal cancer is often associated with increased rates of screening in whites.
The authors say it is difficult to explain why a perception of increased risk, which is significantly higher in African Americans with a family history of CRC than in those without, did not translate into screening. Their findings suggest that other unknown or unmeasured factors may play a role is screening decisions. Additional studies to determine what those factors might be could lead to culturally tailored interventions designed to increase screening rates, which in turn could ultimately improve early detection and reduce colorectal cancer deaths in African Americans. This study suggests that African Americans would benefit from a primary care approach that evaluates their risk factors for colorectal cancer, and provides corresponding recommendations for appropriate screening tests, the authors write.
Regular colorectal cancer screening is one of the most powerful weapons in preventing colorectal cancer. It can, in many cases, prevent colorectal cancer altogether. Experts estimate adherence to national screening guidelines could prevent up to eight in ten deaths from the disease. The American Cancer Society recommends that people at average risk begin screening for colorectal cancer at age 50. Colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, as well as the third leading cause of cancer-related death among both men and women in the United States.
Source: http://www.jhu.edu
This work was a collaboration between researchers at the Baylor College of Medicine, the Oregon National Primate Research Center at the Oregon Health and Science University and the University of Utah Health Sciences.
HOUSTON -- (June 11, 2008) -- The notion that you are what you eat may go back even farther – to your mother, said a Baylor College of Medicine researcher in a report that appears in the current issue of the Journal of Molecular Endocrinology.]]> In some cases, the mothers on the high fat diet did not become obese themselves but their offspring suffered the same ill effects as those of moms who did become obese."We want to understand the mechanisms behind the current epidemic of childhood obesity," said Dr. Kjersti M. Aagaard-Tillery, assistant professor of obstetrics and gynecology at BCM. "What efforts can we take in pregnancy to affect this problem? Is it that the mom is obese or is exposure to a high fat diet the problem?" A consortium of researchers from BCM, the University of Utah Health Sciences in Salt Lake and the Oregon National Primate Research Center teamed up to study what happens to the offspring of non-human primate mothers fed a diet consisting of 35 percent fat. When compared to those who ate a 13 percent fat diet, the offspring of these animals had non-alcoholic fatty liver disease (comparable to that found in obese human youngsters). In fact, their triglycerides (one form of fat measured in blood) were three times higher than those of the normal offspring.
At a molecular level, Aagaard and her collaborators found modifications in the DNA backbone – the histones – of the offspring of the mothers who ate a high fat diet. This is called an epigenetic change, which means that while it does not affect the DNA code per se, it still affects the way that the genes are regulated and the degree to which they are expressed (the so-called "histone code").
"We found that there were genes that were differentially regulated in the livers of the offspring whose mothers had a high fat diet, and that these changes ere associated with histone alterations," she said. "The genes affected were not always those associated with obesity."
She is now trying to find out why these gene changes exist and how they might affect the animals later in life. She is interested in looking at whether they are the direct result of permanent modifications in the histones in both the liver and brain, and whether they further relate to specific changes in the chemical modifications (or methylation) of the regulatory regions of genes.
Others who took part in this work include Kevin Grove and Jacalyn Bishop of the Oregon Health Science University, Oregon National Primate Research Center and Xingrao Ke, Qi Fu, Robert McKnight, and Robert H. Lane of the University of Utah Health Sciences in Salt Lake.
Funding for this work came from the 2007 National Institutes of Health Director's New Innovators Award to Aagaard, the National Institute of Digestive and Diabetes and Kidney Diseases and the National Institute of Child Health and Human Development.
The full report is available at http://jme.endocrinology-journals.org/cgi/reprint/JME-08-0025v1. The abstract is at http://jme.endocrinology-journals.org/cgi/content/abstract/JME-08-0025v1.
Source: http://www.bcm.tmc.edu/
Pinot Noir Genome Sequence Could Help Cut Costs of Wine Production December 20, 2007 By a GenomeWeb staff reporter]]>NEW YORK (GenomeWeb News) – The newly published genome sequence of the pinot noir grape could reduce the cost of producing some popular wines, according to the research team that conducted the study.
The study, led by Riccardo Velasco and colleagues at Italy’s Agrario di San Michele all'Adige, was published in the open-access journal PLoS One this week. The research team used a combination of Sanger sequencing and 454 Life Sciences’ Genome Sequencer 20 to sequence the pinot noir plant’s 500 million base pairs.
The researchers used Sanger sequencing to generate 6.5X coverage and 454 sequencing to produce 4.2X coverage of the Vitis vinifera pinot noir clone ENTAV 115, a variety grown in a range of soils for red and sparkling wines.
Grape vines can be problematic to cultivate and are susceptible to a number of diseases caused by fungi, bacteria, and viruses.
The researchers expect that the pinot noir genome will provide insight into creating disease-resistant grape varieties without altering the quality of the resulting wine.
As part of the sequencing study Velasco and colleagues identified a number of genes that are related to disease-resistance, of which 289 contain one or more SNPs.
The study found that the grape plant has a relatively small genome for a crop plant, with more than two million SNPs and 28,585 genes.
“Pinot Noir has a highly complex heterozygous genome, which presents significant challenges to any sequence and assembly effort,� said 454’s VP of R&D, Michael Egholm, in a statement.
Although this complexity made the sequencing difficult, the researchers said it provided a “massive library of inherent variation� for studying how genes influence plant growth.
The genome also could provide information about pinot noir evolution, which has been complicated by its history of cultivation.
The researchers found that ten out of the plant’s 19 chromosomes resulted from a duplication that occurred shortly after the plant’s lineage diverged from that of the model plants Arabidopsis and poplar.
This genome sequencing “presents an opportunity to direct genetic improvement or disease resistance,� said Brian Dilkes of the University of California Davis’ Genome Center. It also could allow breeding for disease resistance without compromising grape flavor or quality, Dilkes added.
"The sequence of the grape genome, together with the large arsenal of SNP loci, now offers a tool to open a new era in the molecular breeding of grapes,� Velasco said.
Discovery Points to Treatment Approach for Fragile X Syndrome]]>December 20, 2007 -- New research has found that many of the symptoms of fragile X syndrome, the most common cause of inherited mental retardation, can be eliminated in mice by reducing the expression of a single gene in the brain.
The study suggests that the gene is a prime target for drugs to alleviate symptoms of the disorder, for which there is currently no specific treatment.Howard Hughes Medical Institute investigator Mark Bear and his colleagues reported their findings in the December 20, 2007, issue of the journal Neuron. Gül Dölen, a member of Bear's laboratory at Massachusetts Institute of Technology, was the lead author of the research article. Bear and Dölen collaborated with researchers at Brown Medical School, India's National Institute of Mental Health and Neuroscience, and the Tata Institute of Fundamental Research in Bangalore, India.
“The most exciting consequence of that theory was that it might be possible to correct fragile X by dialing back mGluR5 activation.�
Mark F. Bear
Fragile X syndrome is the most common inherited form of mental retardation and is estimated to affect approximately 90,000 people in the United States. The condition is caused by a mutation in the FMR1 gene on the X chromosome that prevents expression of a single protein, fragile X mental retardation protein (FMRP). The effects of fragile X vary between individuals, ranging from learning disability and hyperactivity to severe mental retardation. In addition to cognitive impairment and autistic behavior, children with fragile X can experience epileptic seizures and abnormal growth.
The disorder is caused by loss of a functional version of FMRP. Bear and his colleagues suspected that FMRP might suppress protein synthesis in the brain and work in opposition to metabotropic glutamate receptor-5 (mGluR5), which turns on protein synthesis. “The theory was that when FMRP was removed, protein synthesis was placed on a hair trigger, and that many pathologies of fragile X might be a consequence of that increase in protein synthesis,� he said. “The most exciting consequence of that theory was that it might be possible to correct fragile X by dialing back mGluR5 activation.�
To test this idea, the researchers knocked out one of the two copies of the gene for mGluR5 in mice that also lacked the gene for FMRP. The genetically engineered mice exhibited many of the symptoms observed in humans who have fragile X. By knocking out one copy of mGluR5, the researchers created mice that produced only half the normal amount of mGluR5 protein. And by cutting mGluR5 production in half, the researchers hoped that this would compensate for the lack of FMRP and eliminate the symptoms of fragile X.
“We decided to reduce the mGluR5 levels by 50 percent to reflect what might be a therapeutically relevant condition that would be achievable with carefully titrated drug treatment,� said Bear. “Total knockout of mGluR5 has deleterious effects, whereas reducing it by half is innocuous.�
The researchers found that reducing mGluR5 eliminated many of the symptoms of the disorder. Like humans with fragile X, mice without FMRP experience seizures, impaired memory, and accelerated body growth. When mGluR5 was diminished, these problems were corrected.
The reduction in mGluR5 also compensated for changes in the brain associated with increased protein synthesis. With less mGluR5, the brain of each mouse no longer formed an excessive number of neuronal connections. And the mice did not have a high density of dendritic spines that is characteristic of fragile X syndrome. Furthermore, the total rate of protein synthesis was reduced to normal levels in the brains of fragile X mice with reduced mGluR5.
The results of these experiments suggest drugs that block mGluR5 could prove to be the first effective treatment for fragile X syndrome, said Bear. Pharmaceutical companies have already developed a number of experimental drugs that block mGluR5, he said. Clinical trials are underway, but none of the drugs has yet been approved for humans. To speed drug development, Bear founded Seaside Therapeutics, a company that is now exploring the use of anti-mGluR5 drugs to treat fragile X syndrome.
Next on Bear's scientific agenda is an effort to determine which brain proteins are regulated by FMRP and mGluR5. Such information could help drug designers target pathologies of the disorder more precisely, he said. Bear and his colleagues are also exploring whether FMRP suppresses additional protein synthesis accelerators. These proteins might also make good targets for therapeutic drugs, Bear said.
Finally, he said, defects in the regulation of mGluR5 might also contribute to autism. “A picture is beginning to emerge that many single-gene disorders that cause autism might turn out to be genes that are similarly involved in the negative regulation of protein synthesis,� he said. “Thus, a significant fraction of cases of autism might be accounted for by excessive cerebral protein synthesis. If that were true, then mGluR5 antagonists might be therapeutically useful for much more than just fragile X.�
Source: http://www.hhmi.org