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Category Archives: Transhuman News
Long-term treatment success using gene therapy to correct a lethal metabolic disorder
Posted: October 10, 2014 at 5:47 am
PUBLIC RELEASE DATE:
9-Oct-2014
Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline
New Rochelle, NY, October 9, 2014Excessive and often lethal blood levels of bilirubin can result from mutations in a single gene that are the cause of the metabolic disease known as Crigler-Najjar syndrome type 1 (CNS1). A new gene therapy approach to correcting this metabolic error achieved significant, long-lasting reductions in bilirubin levels in a mouse model of CNS1 and is described in an Open Access article in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Human Gene Therapy website at http://online.liebertpub.com/doi/full/10.1089/hum.2013.233.
In "Life-Long Correction of Hyperbilirubinemia with a Neonatal Liver-Specific AAV-Mediated Gene Transfer in a Lethal Mouse Model of CriglerNajjar Syndrome," Giulia Bortolussi and coauthors from the International Centre for Genetic Engineering and Biotechnology; Centro Studi Fegato, Fondazione Italiana Fegato; and University of Trieste (Trieste, Italy) and Charles University (Prague, Czech Republic), present details of the adeno-associated virus (AAV)-mediated gene therapy approach they used to correct the metabolic disorder that causes hyperbilirubinemia in CNS1. The researchers reported 70-80% reductions in plasma bilirubin levels early on among treated animals, with about 50% reductions maintained throughout the study. The authors compared the effectiveness of two delivery strategies: targeting the therapeutic gene directly to the liver or, preferably, to skeletal muscle. They discuss the implications of the different results they obtained with each approach.
"CNS1 is an outstanding model for in vivo gene therapy with easily measured and clinically relevant metabolic endpoints," says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.
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About the Journal
Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Its sister journals, Human Gene Therapy Methods, published bimonthly, focuses on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development, published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. Tables of contents and sample issues for all three publications may be viewed on the Human Gene Therapy website at http://www.liebertpub.com/hgt.
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Long-term treatment success using gene therapy to correct a lethal metabolic disorder
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Human Genetics Molecular Biology of Gene – Video
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Human Genetics Molecular Biology of Gene
Human Genetics Molecular Biology of the Gene.
By: GEBRI usc
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Human Genetics Molecular Biology of Gene - Video
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University of Chicago establishes national center to study genetics of drug abuse in rats
Posted: at 5:46 am
PUBLIC RELEASE DATE:
9-Oct-2014
Contact: Kevin Jiang kevin.jiang@uchospitals.edu 773-795-5227 University of Chicago Medical Center @UChicagoMed
The National Institute on Drug Abuse (NIDA) has awarded the University of Chicago a $12 million, five year grant to establish a national Center of Excellence to study drug abuse-associated behaviors by conducting research with rats.
Led by Abraham Palmer, PhD, associate professor of human genetics, the NIDA Center for Genome-Wide Association Studies in Outbred Rats will combine complex behavioral studies with recent technological advances in rat genetics to help scientists shed light on the genes behind drug addiction.
Rats have a long and storied history as an important animal model for research, especially in behavioral studies. But in recent decades, the use of rats has given way to mice because of innovations in the manipulation of mouse genomes. This shift has affected certain research fields, particularly the study of drug abuse and addiction, where behavioral tasks are often too complex for mice to perform. That's led to a slowdown in research aimed at revealing the genetics thought underlie drug abuse-related behaviors.
"The odds of permanently recovering from drug addiction are low and there is currently very little understanding of why that is," Palmer said. "With an animal system, we have a powerful advantage in that once we've found a genetic location or pathway, we can easily manipulate the gene and measure the resulting effects. The use of rats is critical because many of the behaviors we will study have proven difficult or impossible to adapt for mice."
A rat revival
To shed light on the genetics behind complex traits such as drug abuse behavior, the researchers will utilize genome-wide association studies (GWAS) an examination of the entire genomes of different individuals to reveal genetic variants linked with particular traits. Research groups around the country will perform experiments exploring separate behaviors, and send samples to UChicago for genetic analysis. This allows the center to study the genetics of multiple aspects of drug abuse efficiently and at a much more rapid pace than previously possible.
While most animal studies use almost genetically identical subjects, GWAS studies require large numbers of unrelated individuals. The center will support a comprehensive breeding program that provides researchers with a unique population of rats that have been bred to maintain as much genetic diversity as possible. Studies will be performed on both male and female rats to explore the relationship between gender, drug abuse behavior and genetics.
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University of Chicago establishes national center to study genetics of drug abuse in rats
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Multiple neurodevelopmental disorders have a common molecular cause
Posted: at 5:46 am
PUBLIC RELEASE DATE:
9-Oct-2014
Contact: Mary Beth O'Leary moleary@cell.com 617-397-2802 Cell Press @CellPressNews
Neurodevelopmental disorders such as Down syndrome and autism-spectrum disorder can have profound, lifelong effects on learning and memory, but relatively little is known about the molecular pathways affected by these diseases. A study published by Cell Press October 9th in the American Journal of Human Genetics shows that neurodevelopmental disorders caused by distinct genetic mutations produce similar molecular effects in cells, suggesting that a one-size-fits-all therapeutic approach could be effective for conditions ranging from seizures to attention-deficit hyperactivity disorder.
"Neurodevelopmental disorders are rare, meaning trying to treat them is not efficient," says senior study author Carl Ernst of McGill University. "Once we fully define the major common pathways involved, targeting these pathways for treatment becomes a viable option that can affect the largest number of people."
A large fraction of neurodevelopmental disorders are associated with variation in specific genes, but the genetic factors responsible for these diseases are very complex. For example, whereas common variants in the same gene have been associated with two or more different disorders, mutations in many different genes can lead to similar diseases. As a result, it has not been clear whether genetic mutations that cause neurodevelopmental disorders affect distinct molecular pathways or converge on similar cellular functions.
To address this question, Ernst and his team used human fetal brain cells to study the molecular effects of reducing the activity of genes that are mutated in two distinct autism-spectrum disorders. Changes in transcription factor 4 (TCF4) cause 18q21 deletion syndrome, which is characterized by intellectual disability and psychiatric problems, and mutations in euchromatic histone methyltransferase 1 (EHMT1) cause similar symptoms in a disease known as 9q34 deletion syndrome.
Interfering with the activity of TCF4 or EHMT1 produced similar molecular effects in the cells. Strikingly, both of these genetic modifications resulted in molecular patterns that resemble those of cells that are differentiating, or converting from immature cells to more specialized cells. "Our study suggests that one fundamental cause of disease is that neural stem cells choose to become full brain cells too early," Ernst says. "This could affect how they incorporate into cellular networks, for example, leading to the clinical symptoms that we see in kids with these diseases."
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The American Journal of Human Genetics, Chen et al.: "Molecular convergence of neurodevelopmental disorders."
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Multiple neurodevelopmental disorders have a common molecular cause
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Reproducibility score for SNPs associated with human disease in GWAS
Posted: at 5:46 am
To reduce false positives when identifying genetic variations associated with human disease through genome-wide association studies (GWAS), Dartmouth researchers have identified nine traits that are not dependent on P values to predict single nucleotide polymorphisms (SNP) reproducibility as reported in Human Genetics on October 2, 2014.
Reproducibility rates of SNPs based solely on P values is low. Dartmouth authors' analysis of GWAS studies published in Human Genetics showed a 1-5 percent replication rate.
"It is important to improve our ability to select SNPs for validation using a formalized process. In this paper, we propose a combination of traits that improve replication success," said first author Ivan P. Gorlov, PhD, DSC, associate professor of Community and Family Medicine, Geisel School of Medicine at Dartmouth.
The team assigned a value of zero or one to nine different predictors. To compute the Replication Score (RS), one totals the individual scores for all significant predictors. The predictors include "Online Mendelian Inheritance in Man" (OMIM, a list of genetically caused diseases), receptors, kinases, growth factors, transcription factors, tissue specific, plasma membrane localization, nuclear localization and conversation index. The authors provided detailed information to construct the RS in supplementary material to the paper.
An RS score is not disease specific but shows the potential for impact on human disease. "The disease-associated genes have something in common," said Gorlov. "And we know what specific characteristics should be present to ensure the SNP is likely to be replicated."
Gorlov says the empirical model can be used to select SNPs for validation and prioritization. "We believe that RS-based SNP prioritization may provide guidance for more targeted and powered approach to detecting the disease-associated SNPs with small effect size," he concluded.
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The above story is based on materials provided by The Geisel School of Medicine at Dartmouth. Note: Materials may be edited for content and length.
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Reproducibility score for SNPs associated with human disease in GWAS
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23andMe: Inside the DNA revolution | Full Interview Fortune MPW – Video
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23andMe: Inside the DNA revolution | Full Interview Fortune MPW
A conversation about biology, technology and the future of disease prevention Want to see more Fortune Video? Subscribe to our channel ...
By: Fortune Magazine
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23andMe: Inside the DNA revolution | Full Interview Fortune MPW - Video
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Asian carp DNA found in Kzoo River – Video
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Asian carp DNA found in Kzoo River
Officials say genetic material of Asian carp has been found in a river in the Kalamazoo River in southwestern Michigan. (Oct. 7, 2014)
By: WOOD TV8
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Asian carp DNA found in Kzoo River - Video
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DNA (DENTAL NURSE ART BAND) POLTEKKES KEMENKES MAKASSAR – Video
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DNA (DENTAL NURSE ART BAND) POLTEKKES KEMENKES MAKASSAR
(DNA) Jurusan Kep.gigi WE WILL NOT GO DOWN IN BEDAH BUKU SETIA FURQON KHOLID.
By: fivy suriyanisuhar
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DNA (DENTAL NURSE ART BAND) POLTEKKES KEMENKES MAKASSAR - Video
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DNA Sequencing – Macrogen Clinical Laboratory – Video
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DNA Sequencing - Macrogen Clinical Laboratory
DNA Sequencing is the process of determining the order of nucleotides within a DNA molecule. It includes any method or technology that is used to determine the order of four bases. Macrogen...
By: Macrogen Clinical Laboratory
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DNA Sequencing - Macrogen Clinical Laboratory - Video
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DANIELESCU RIDICAT DE DNA – Video
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DANIELESCU RIDICAT DE DNA
08.10.2014.
By: Mihaela Dan Press
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DANIELESCU RIDICAT DE DNA - Video
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