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Category Archives: Genetic Medicine
Diseases that strike different parts of the bodyand that don't seem to resemble each other at allmay actually have a lot in common.
Scientists have identified the genetic basis for many separate diseases. Now, some researchers are looking at how the genes interact with each other. They are finding that a genetic abnormality behind one illness may also cause other, seemingly unrelated disorders. Sometimes diseases are tangentially linked, having just one gene in common. But the greater the number of shared genetic underpinnings a group of diseases has, the greater the likelihood a patient with one of the illnesses will contract another.
Researchers have found evidence, for example, that there is a close genetic relationship between Crohn's disease, a gastrointestinal condition, and Type 2 diabetes, despite the fact the two conditions affect the body in very distinct ways. Other illnesses with apparently close genetic links are rheumatoid arthritis and Type 1 diabetes, the form of the disease that usually starts in childhood, said Dr. Joseph Loscalzo, chairman of the department of medicine at Brigham and Women's Hospital in Boston.
This network approach, known among scientists as systems biology, could change the way medical specialists view and treat disease, according to some researchers. Rather than only looking to repair the parts of the body that are directly affected by illness, "we should be looking at what the wiring diagram [inside of cells] looks like," said Dr. Albert-Lszl Barabsi, a physicist at Northeastern University's Center for Complex Network Research in Boston.
The information could help better predict a person's risk of developing diseases, researchers say. It also could aid drug development. By figuring out which proteins are most critical to the normal functioning of the body, pharmaceutical companies could target those key proteins to treat disease. In some cases, drug companies may want to avoid interfering with key proteins to avoid too many unintended side effects, says Marc Vidal, director of the Center for Cancer Systems Biology at Dana-Farber Cancer Institute in Boston.
Since all the DNA in the human body was first sequenced in 2000, some 4,000 diseases with a known genetic basis have been identified, according to the National Institutes of Health. But only about 250 of those diseases have treatments, leaving many genetic puzzles left to untangle.
Scientists have long known that proteins and other molecules in the body don't act alone. In order for the body to operate efficiently, biological substances must bind to or pass chemical messages to each other to start and stop working. The system is complex: Each gene is thought to produce, on average, five separate substances, mostly proteins, and these products interact with each other. When a protein, or group of proteins, malfunctions, it appears to give rise to a variety of distinct illnesses.
Barabsi and his colleagues set out to see which diseases shared genetic underpinnings. They used information from a vast database at Johns Hopkins University in Baltimore that pulled together research from around the world on diseases and genes they were linked to. The scientists then mapped out a network indicating which diseases were seemingly connected to each other through common genes.
Of the 1,284 diseases mapped, nearly 900 had genetic links to at least one other disease. And 516 of these formed a so-called disease cluster, in which illnesses, mainly cancers, were linked to each other through multiple genetic connections.
Click here to read more from The Wall Street Journal.
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The genetic links between different diseases
--Study lends support to safe use for therapy
Newswise A team of researchers from Johns Hopkins University and the National Human Genome Research Institute has evaluated the whole genomic sequence of stem cells derived from human bone marrow cellsso-called induced pluripotent stem (iPS) cellsand found that relatively few genetic changes occur during stem cell conversion by an improved method. The findings, reported in the March issue of Cell Stem Cell, the official journal of the International Society for Stem Cell Research (ISSCR), will be presented at the annual ISSCR meeting in June.
Our results show that human iPS cells accrue genetic changes at about the same rate as any replicating cells, which we dont feel is a cause for concern, says Linzhao Cheng, Ph.D., a professor of medicine and oncology, and a member of the Johns Hopkins Institute for Cell Engineering.
Each time a cell divides, it has the chance to make errors and incorporate new genetic changes in its DNA, Cheng explains. Some genetic changes can be harmless, but others can lead to changes in cell behavior that may lead to disease and, in the worst case, to cancer.
In the new study, the researchers showed that iPS cells derived from adult bone marrow cells contain random genetic changes that do not specifically predispose the cells to form cancer.
Little research was done previously to determine the number of DNA changes in stem cells, but because whole genome sequencing is getting faster and cheaper, we can now more easily assess the genetic stability of these cells derived by various methods and from different tissues, Cheng says. Last year, a study published in Nature suggested higher than expected cancer gene mutation rates in iPS cells created from skin samples, which, according to Cheng, raised great concerns to many in the field pertaining to usefulness and safety of the cells. This study analyzed both viral and the improved, nonviral methods to turn on stem cell genes making the iPS cells
To more thoroughly evaluate the number of genetic changes in iPS cells created by the improved, non-viral method, Chengs team first converted human blood-forming cells or their support cells, so-called marrow stromal cells (MSCs) in adult bone marrow into iPS cells by turning on specific genes and giving them special nutrients. The researchers isolated DNA from--and sequenced--the genome of each type of iPS cells, in comparison with the original cells from which the iPS cells were derived.
Cheng says they then counted the number of small DNA differences in each cell line compared to the original bone marrow cells. A range of 1,000 to 1,800 changes in the nucleic acid letters A, C, T and G occurred across each genome, but only a few changes were found in actual genes--DNA sequences that act as blueprints for our bodys proteins. Such genes make up two percent of the genome.
The blood-derived iPS cells contained six and the MSC-derived iPS cells contained 12 DNA letter changes in genes, which led the researchers to conclude that DNA changes in iPS cells are far more likely to occur in the spaces between genes, not in the genes themselves.
Next, the investigators examined the severity of the DNA changes--how likely each one would disrupt the function of each gene. They found that about half of the DNA changes were silent, meaning these altered blueprints wouldnt change the nucleic acid building code for its corresponding protein or change its function.
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Improved Adult-Derived Human Stem Cells Have Fewer Genetic Changes Than Expected
The Domino technology uses a plastic chip that can perform 20 genetic tests from a single drop of blood.
You wouldn't know it from appearances, but a metal cube the size of a toaster, created at the University of Alberta, is capable of performing the same genetic tests as most fully equipped modern laboratoriesand in a fraction of the time.
At its core is a small plastic chip developed with nanotechnology that holds the key to determining whether a patient is resistant to cancer drugs or has viruses like malaria. The chip can also pinpoint infectious diseases in a herd of cattle.
Talk about thinking outside the box.
Dubbed the Domino, the technologydeveloped by a U of A research teamhas the potential to revolutionize point-of-care medicine. The innovation has also earned Aquila Diagnostic Systems, the Edmonton-based nano startup that licensed the technology, a shot at $175,000 as a finalist for the TEC NanoVenturePrize award.
Were basically replacing millions of dollars of equipment that would be in a conventional, consolidated lab with something that costs pennies to produce and is field portable so you can take it where needed. Thats where this technology shines, said Jason Acker, an associate professor of laboratory medicine and pathology at the U of A and chief technology officer with Aquila.
The Domino employs polymerase chain reaction technology used to amplify and detect targeted sequences of DNA, but in a miniaturized form that fits on a plastic chip the size of two postage stamps. The chip contains 20 gel postseach the size of a pinheadcapable of identifying sequences of DNA with a single drop of blood.
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Thats the real value propositionbeing able to do multiple tests at the same time, Acker said, adding that the Domino has been used in several recently published studies, showing similar accuracy to centralized labs.
The Domino effect: Personalized medicine
SAN DIEGO--(BUSINESS WIRE)--
Pathway Genomics Corporation, a genetic testing laboratory specializing in nutrition and exercise response, inherited disease, prescription drug response and health condition risks, has established a world-leading scientific advisory board. Among the board members are James Fowler, Ph.D., professor of medical genetics at UCSD School of Medicine, Christoph Lange, Ph.D., associate professor of biostatistics at Harvard University School of Public Health, and Nicholas Schork, Ph.D., director of bioinformatics and biostatistics at the Scripps Translational Science Institute.
Additionally, the companys internal computational and bioinformatics team is led by Lixin Zhou, Ph.D., former senior scientist at Illumina and former collaborative bioinformatics investigator at The Institute for Genomic Research, an organization of The J. Craig Venter Institute.
Working with innovators in specific and technical fields helps Pathway bring highly accurate, useful and actionable information to physicians and their patients, said Michael Nova, M.D., Pathway Genomics chief medical officer. Were committed to seeking out this actionable genetic information through computational biology methods, and cloud-based bioinformatics.
An acclaimed behavioral geneticist, James Fowler, Ph.D., is currently a professor of medical genetics at UCSD School of Medicine, and is world-renowned for his breakthrough discoveries in genetics and social networking, behavioral economics, cooperation, and political behavior.
Christoph Lange, Ph.D., is an assistant professor of medicine at Harvard Medical School and an associate professor of biostatistics at Harvard School of Public Health. Langes current research interests fall into the broad areas of statistical genetics and generalized linear models.
Nicholas J. Schork, Ph.D., is a professor at The Scripps Research Institute in the department of molecular and experimental medicine and director of bioinformatics and biostatistics at the Scripps Translational Science Institute. Schorks research focuses are in quantitative human genetics and integrated approaches to complex biological and medical problems. He has published over 350 scientific articles and book chapters analyzing complex, multifactorial traits and diseases.
Pathways scientific advisory board consists of 10 leaders in various fields including behavioral genetics, bioinformatics, biostatistics, endocrinology, human epigenetics, metabolism, nutrigenomics, nutrition, obesity and exercise genetics, oncology, and weight management. To view the companys full scientific advisory board, visit http://www.pathway.com/sab.
About Pathway Genomics
Pathway Genomics owns and operates an on-site genetic testing laboratory that is accredited by the College of American Pathologists (CAP), accredited in accordance with the U.S. Health and Human Services Clinical Laboratory Improvement Amendments (CLIA) of 1988, and licensed by the state of California. Using only a saliva sample, the company incorporates customized and scientifically validated technologies to generate personalized reports, which address a variety of medical issues, including an individuals carrier status for recessive genetic conditions, food metabolism and exercise response, prescription drug response, and propensity to develop certain diseases such as heart disease, type 2 diabetes and cancer. For more information about Pathway Genomics, visit http://www.pathway.com.
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Pathway Genomics Adds Prominent Bioinformatics Experts to Scientific Advisory Board
Public release date: 25-Apr-2012 [ | E-mail | Share ]
Contact: Zachary Rathner Zachary.Rathner@oup.com 301-841-1286 Journal of the National Cancer Institute
There is an association between the rs1051730-rs16969968 genotype and objective measures of tobacco exposure, which indicates that lung cancer risk is largely, if not entirely, mediated by level of tobacco exposure, according to a study published April 25 in the Journal of the National Cancer Institute.
The rs1051730-rs16969968 genotype is known to be associated with heaviness of smoking, lung cancer risk, and other smoking-related outcomes. Prior studies have generally depended on self-reported smoking behavior, which may have underestimated associations and masked the contribution of heaviness of smoking to the associations of these polymorphisms with lung cancer and other health outcomes.
In order to determine the association between the rs1051730-rs16969968 genotype and self-reported cigarette consumption and plasma or serum cotinine levels, Marcus R. Munaf, Ph.D., of the School of Experimental Psychology at the University of Bristol and colleagues, examined data from six independent studies that looked at self-reported daily cigarette consumption and plasma or serum cotinine levels among cigarette smokers and conducted a meta-analysis of pooled per-allele effects. In addition, the researchers looked at the link between the genotypes and lung cancer risk using published data on the association between cotinine levels and lung cancer risk.
The researchers found that the rs1051730-rs16969968 genotype is strongly associated with tobacco exposure measured through cotinine levels, and that the association is strong even after adjustment for self-reported cigarette consumption. "These data therefore support the conclusion that association of rs1051730-rs16969968 genotype with lung cancer risk is mediated largely, if not wholly, via tobacco exposure," the researchers write.
The researchers point out certain limitations of the study, however, namely that the data were drawn from disparate studies from various populations. The data also relies on current smoking measures, rather than lifetime exposure, which is more strongly associated with lung cancer risk.
However, they have confidence in their results, which show that phenotype precision is important to uphold in GWAS studies, rather than ever-larger sample sizes, they say. "The use of objective measures of smoking behavior in genome-wide studies may reveal novel variants associated with these outcomes, which would be undetectable using conventional self-report measures."
In an accompanying editorial, Margaret R. Spitz, M.D., MPH, of the Department of Molecular and Cellular Biology at the Dan L. Duncan Cancer Center at Baylor College of Medicine, writes that these findings "confirm that cigarettes per day is an imprecise measure of nicotine consumption, and favor the interpretation that the association between these variants and lung cancer is mediated by smoking. But the degree to which the association is mediated by smoking is yet to be determined." They add that more studies, including mouse and cellular models, along with emerging metabolic markers, "may help tease apart the direct and indirect associations of these variants with lung cancer risk."
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Genetic variants, tobacco exposure and lung cancer risk
Newswise ATLANTA, Ga. Thomas R. Terrell, MD presented Prospective Cohort Study of the Association of Genetic Polymorphisms and Concussion Risk and Postconcussion Neurocognitive Deficits in College Athletes at the 21st American Medical Society for Sports Medicine Annual Meeting in Atlanta, Ga. on April 23, 2012.
A multi-center prospective cohort study of over 3,200 college and high school athletes was designed to look at the association of genetic polymorphisms with risk of acute concussion and for an associative link with longer duration of symptoms. Following analysis trying to link certain genetic polymorpisms, those evaluated did not show an association with prospective concussions, although some association was found in a pooled analysis of self-reported and prospective concussions.
Dr. Terrell, a two-time AMSSM Foundation Research Award winner, commented, Although we did not find an association of these genetic factors in association prospectively with concussions, the next segment of our research is to evaluate other genetic factors, particularly for associations with severe or recurrent concussions. He was optimistic about possible associations and said, As we look at further data and expand our numbers of concussions included in the study, part of the Tau gene and other genetic polymorphisms have a link in explaining neurocognitive recovery
The AMSSM annual conference features lectures and research addressing the most challenging topics in sports medicine today including prevention of sudden death, cardiovascular issues in athletes, concussion, biologic therapies, and other controversies facing the field of sports medicine.
More than 1,200 sports medicine physicians from across the United States and 12 countries around the world are attending the meeting.
Dr. Terrell is an Associate Professor at the University of Tennessee Graduate School of Medicine and holds a Certificate of Added Qualification in Sports Medicine.
The AMSSM is a multi-disciplinary organization of sports medicine physicians whose members are dedicated to education, research, advocacy, and the care of athletes of all ages. Founded in 1991, the AMSSM is now comprised of more than 2,000 sports medicine physicians whose goal is to provide a link between the rapidly expanding core of knowledge related to sports medicine and its application to patients in a clinical setting.
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Genetic Associations with Concussions Discussed by AMSSM Researcher