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Category Archives: Genome

Dr. Thomas Merritt – Downside to genome sequencing? – Video

Posted: May 1, 2014 at 5:47 am


Dr. Thomas Merritt - Downside to genome sequencing?
Dr. Thomas Merritt answers the question, "Do you think there is a downside to having your genome sequenced?" submitted by students at St. Lewis Academy in St...

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Genome databases – Video

Posted: April 30, 2014 at 9:45 am


Genome databases
Lecture 3 - DNA and Protein databases - genome databases.

By: Rita Margarida Teixeira Ascenso

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Tsetse Genome – A Scientific Breakthrough – Video

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Tsetse Genome - A Scientific Breakthrough

By: YSPH1

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GWAS study ties ABCC9 anomalies, sulfonylurea exposure to HS-Aging

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PUBLIC RELEASE DATE:

29-Apr-2014

Contact: Laura Dawahare laura.dawahare@uky.edu University of Kentucky

LEXINGTON, Ky. (April 29, 2014) -- A genome-wide association study (GWAS) led by Peter Nelson, MD, PhD, of the Sanders-Brown Center on Aging at the University of Kentucky, and David Fardo, PhD, of UK's Department of Biostatistics, has provided new insight into Hippocampal Sclerosis of Aging (HS-A), a common disease affecting the elderly.

Researchers from 16 different institutions compared 363 persons with autopsy-proven HS-A to a control group of 2,303 other individuals in an attempt to identify genetic predisposition to HS-Aging.

Dr. Nelson and his team found that small changes in the ABCC9 gene -- also known as Sulfonylurea Receptor 2 -- strongly paralleled the incidence of HS-Aging. Further statistical analysis demonstrated a link between the use of sulfonylurea, a medication commonly used to treat diabetes, and an increased risk for HS-A.

"This is the first genome-wide association study of its kind, and it has terrific statistical power," Dr. Nelson said. "While certainly there's a lot more work to be done to confirm the drug-disease interaction, this study nonetheless describes a novel dementia risk factor."

GWAS studies are a relatively new way to explore the linkage between any disease and the genetic factors that may contribute to them. Using the DNA of similar people with the target disease and without, millions of genetic variants are read and analyzed in an attempt to mark a region of the human genome that influences the risk of the target disease. In contrast to methods which specifically test one or a few genetic regions, the GWA studies investigate the entire genome.

"This work confirms that the problems that occur in the brains of the elderly are complicated -- but until we delve deeper into that complexity, we will be frustrated in our goal of finding new cures for these horrible diseases," Dr. Nelson said. "If further research confirms the genetic link we have identified in this study, it might inform new strategies to search for cures."

The Sanders-Brown Center on Aging is a worldwide leader in research on HS-A, a condition that affects up to 15% of individuals over age 85. Its symptoms are so similar to those of Alzheimer's disease that patients are often misdiagnosed with the latter. Currently, the only way to confirm a diagnosis of HS-A is by autopsy.

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GWAS study ties ABCC9 anomalies, sulfonylurea exposure to HS-Aging

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SDSC resources, expertise used in genomic analysis of 115 year-old woman

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PUBLIC RELEASE DATE:

29-Apr-2014

Contact: Jan Zverina jzverina@sdsc.edu 858-534-5111 University of California - San Diego

A team of researchers investigating the genome of a healthy supercentenarian since 2011 has found many somatic mutations permanent changes in cells other than reproductive ones that arose during the woman's lifetime. Led by Erik Sistermans and Henne Holstege from the VU University Medical Center in Amsterdam, the team recently published its findings in the journal Genome Research as reported by GenomeWeb.

While previous studies have examined mutations that arise in certain disease conditions such as leukemia, Sistermans said that it was not well known how many mutations might appear in the genomes of healthy cells, according to the GenomeWeb report.

At the time of her death at the age of 115, the subject woman, called W115 by the researchers, was the second oldest person in the world and showed no signs of vascular disease or dementia. By donating her body to science, she allowed researchers to study her organs and genome.

The researchers hypothesized that white blood cells, which divide frequently, would have many more somatic mutations than brain cells, which seldom divide. Thus the whole genomes of W115's blood and brain cells were sequenced using SOLiD technology from Life Technologies. Analyses were then done to look for mutations present in the blood cells but not the brain cells.

These analyses involved numerous computations, some of which were done by Wayne Pfeiffer on the Triton cluster at the San Diego Supercomputer Center at the University of California, San Diego under a National Institutes of Health grant. Pfeiffer said that the initial analyses identified thousands of putative somatic mutations, many of which were incorrect because of sequencing errors. Filters were subsequently developed to select the mutations most likely to be somatic.

Two types of mutations were considered: single nucleotide variants (SNVs) and short insertions or deletions (indels). Filtering of the latter was particularly compute-intensive and was done at SDSC. Thousands of core hours were consumed, and some steps required more than 64 gigabytes of shared memory, according to Pfeiffer.

After filtering, many of the highly likely and moderately likely somatic mutations were tested by targeted sequencing using newer Ion PGM sequencers, also from Life Technologies.

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How the koala retrovirus genome evolved

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Retroviruses invaded the genome of koalas with strongly pathological effects: the viruses weaken the immune defense and threaten the viability of the already reduced koala population. An international team of scientists from Europe and North America now applied the technique of hybridisation capture to analyse the entire genome of koala retroviruses and used museum samples to monitor its variation across 130 years. The findings were just published in the scientific online-journal PLOS ONE.

Unlike other viruses, retroviruses must copy their genetic material into the host genome as part of their life cycle. Occasionally, a retrovirus may integrate into the reproductive cells of the host which give rise to future generations, thus becoming a permanent part of the host genome. The koala retrovirus (KoRV) is the pathogen of the Koala Immune Deficiency Syndrome (KIDS), an AIDS-like immunodeficiency. Many generations of the koala population suffered during the process of retroviral endogenisation, the process of initial germ line invasion. KoRV is ubiquitous among northern Australian koalas, but is less common in southern Australian mainland and island populations.

In order to find out how retroviruses invade the germ lines of their hosts, an international team of scientists from the Leibniz Institute for Zoo and Wildlife Research (IZW) in Berlin, the California State University, the Zoo in Vienna, the National Museum of Natural History in Washington and the University of Illinois at Urbana-Champaign applied a technique known as hybridisation capture. This method permits the identification of entire genome sequences of the KoRV, the only known retrovirus currently invading its host germ line, from koala museum skins from the late 19th and across the 20th century and therefore were able to study 130 years of KoRV evolution.

Previous analyses by the team, employing Polymerase Chain Reaction (PCR) based methods, were only able to isolate a single viral gene with a great deal of effort. Using the technique of hybridisation capture, the full retrovirus genome and the location of the retrovirus within the koala genome could be simultaneously examined with far less effort. During hybridisation capture, the library DNA which contains the sequence of the KoRV is immobilised on beads and serves as bait. The targeted DNA from different samples binds to them and the non-specific DNA is washed away. With this method, the scientists could find sequences at high coverage across the full length of the KoRV from both museum samples and modern genomic DNA.

The application of complex mathematical protein modelling demonstrated that selection pressure on the virus to change appears to be very mild. This is why the scientists concentrated on the envelope gene which allows the virus to bind to and invade cells. Overall, the virus was very stable and changed little. The results suggest that for ca. 130 years, the entire proviral genome appeared to be conserved across time in sequence, protein structure and transcriptional binding sites. Newly described and possibly more pathogenic variants known as KoRV-B and KoRV-J were not found in museum specimens, supporting the hypothesis that they have arisen only recently. This also indicates that while generally stable, KoRV may be able to change quickly with unforeseen pathological outcome.

The results suggest that the endogenisation of a retrovirus may happen frequently and rather rapidly, initially without much change inside the virus and that becoming a part of the genome of all members of a host species takes a very long time said Prof Alex Greenwood, the principal investigator of the study. The findings indicate that the formation of a large part of mammalian genomes involved rapid events within individuals or populations but took a very long time to become a standard feature of the species. This suggests that such processes may be happening right now unobserved in many species.

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The above story is based on materials provided by Forschungsverbund Berlin e.V. (FVB). Note: Materials may be edited for content and length.

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Like puzzle pieces, 3-D genomics holds a key to classifying human diseases

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PUBLIC RELEASE DATE:

29-Apr-2014

Contact: Cynthia Lee cynthia.lee@mcgill.ca 514-398-6754 McGill University

To solve a puzzle, you need to recognize shapes, patterns and a particular kind of order. In much the same way, researchers at McGill University have discovered that the 3D shape of a leukemia cell's genome holds a key to solving the puzzle of human diseases. The researchers report their findings in the open access journal Genome Biology.

McGill professor Jose Dostie, a researcher in the Faculty of Medicine in the department of Biochemistry, focused on the shape made by the region spanning the Homeobox A (HOXA) genes in human cells -- a set of 11 genes encoding proteins that are highly relevant to numerous types of cancers. Dostie and colleagues discovered that the shape of this region of the genome was excellent at indicating the subtype of leukemia it comes from. These initial results suggest that 3D genomics might be a way of improving personalised treatment, though application in the clinic is a long way off.

"I have been interested in understanding the role of genome folding with regards to human health and disease," says Dostie, who is also a researcher at the Goodman Cancer Research Centre. "My approach uses technologies that detect which piece of DNA is close to which one, such that we can reconstruct how the genome is folded in three dimensions by piecing this information together as if it were a puzzle".

Dostie and the all-McGill team study the organization of entire genomes and of specific regions relevant to human diseases. The HOXA gene cluster is one of these regions that become improperly regulated in many types of cancers.

"Previous studies have shown that looking at gene expression -- the specific proteins produced by the genes -- is a good predictor of whether patients have leukemia", says Prof. Mathieu Blanchette, a co-author on the study and an assistant professor at McGill in the School of Computer Science. "We found that different types of leukemia cells also have a distinctive chromatin interaction how the chromatin that makes up the genome is folded."

It is not clear at the moment whether the genome shape plays a role in causing the cancer, or whether the cancer causes the genome to change shape. Further studies are needed to determine whether genome shape is as good at indicating other types of cancer.

"Our study validates a new research avenue: the application of 3D genomics for developing medical diagnostics or treatments that could be explored for diseases where current technologies, including gene expression data, have failed to improve patient care," says Dostie, "While the use of 3D genomics in the clinic is still remote when considering the technical challenges required for translating the information to the bedside, we discovered a new approach for classifying human disease that must be explored further, if only for what it can reveal about how the human genome works."

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Like puzzle pieces, 3-D genomics holds a key to classifying human diseases

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Precision BioSciences Announces Expansion of Genome Engineering Partnership with Syngenta

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Research Triangle Park, North Carolina (PRWEB) April 30, 2014

Precision BioSciences, Inc., the genome editing company, today revealed that it has been working with Syngenta to develop advanced agricultural products using the first fully-synthetic genome editing technology. Researchers at Syngenta have successfully used engineered nucleases based on Precisions proprietary ARCUS technology to insert genes of interest into desired locations in the corn genome with unprecedented efficiency. The use of this technology provides plant researchers with a powerful and efficient new method for accelerating the development of greatly needed agricultural products.

The ARCUS platform is Precisions newest genome editing technology and is the result of a multi-year internal R&D program devoted to developing a next-generation editing technology with both the target site flexibility of a TALEN or CRISPR and the high selectivity of a Meganuclease. The ARCUS-derived nucleases were found to be highly effective, leading to an extension of the Precision-Syngenta collaboration.

We are thrilled by the results that Syngenta has achieved using our new ARCUS platform, said Derek Jantz, Precision BioSciences co-founder and Vice President of Scientific Development. They have an exceptional R&D team and we look forward to building on that relationship into the future. While we are hesitant to draw too many conclusions at this point, early results from partners like Syngenta suggest that ARCUS represents a significant step forward in the field of genome editing.

About Precision BioSciences Precision BioSciences mission is to continually provide, improve, and enable the worlds most powerful genome engineering technology. Precisions proprietary genome editing technologies enable the production of highly specific nucleases that can insert, remove, and modify DNA at essentially any location in a complex genome.

Precision BioSciences vision is to be the conduit through which the worlds greatest genome engineering challenges are solved. Precision has successfully utilized its approach to create innovative products in partnerships with many of the worlds largest biopharmaceutical and agbiotech firms. Internally, Precision is developing genome editing-based product leads for human therapeutic, agricultural and biologics manufacturing applications. For additional information, please visit http://www.precisionbiosciences.com.

Contact: Precision BioSciences: Chelsea Lynam, phone: +1 919 314-5512 E-mail: chelsea.lynam(at)precisionbiosciences(dot)com

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Phi X174 genome structure – Video

Posted: April 27, 2014 at 2:44 pm


Phi X174 genome structure
For more information, log on to- http://shomusbiology.weebly.com/ This bacteriophage lecture explains the genome structure of bacteriophage phi X174. Downloa...

By: Suman Bhattacharjee

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Packaging of a genome in phage head – Video

Posted: April 26, 2014 at 6:47 am


Packaging of a genome in phage head
For more information, log on to- http://shomusbiology.weebly.com/ This bacteriophage lecture explains the bacteriophage genome assembly and the packaging of ...

By: Suman Bhattacharjee

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