Category Archives: Transhuman News

The Federal Court has finished hearing an appeal against a patent granted to two US companies for identifying genetic traits in cattle.

Research and marketing bodies Meat and Livestock Australia (MLA) and Dairy Australia launched legal action against the patent holders, Cargill USA and Branhaven LLC, after losing an earlier appeal before the Australian Patent Office.

Cargill is a major global commodities giant, but did not defend the appeal, while little is known about Branhaven except that it acquired the patent after it bought many of the assets of a biotechnology company called Metamorphix when it liquidated in 2011.

A hearing into the matter started last month and ended on Wednesday afternoon, lasting six and a half days in total.

MLA, beef and dairy farmers, and livestock researchers allege the patent could restrict access to genomic testing and research into cattle genetics because it could give Cargill and Branhaven the right to license service providers or charge licensing fees for genomic testing.

These concerns were similar to those raised before the High Court in the landmark breast cancer gene case.

University of Queensland intellectual property expert Professor Matthew Rimmer told the ABC the case was a "test of the limits and boundaries" of what is patentable in Australia.

On both sides, some of Australia's top intellectual property lawyers argued before Justice Jonathan Beach, with Christian Dimitriadis SC appearing for Branhaven, and Katrina Howard SC appearing for MLA.

MLA argued before the court the broadest claim in the patent potentially extends to nearly two thirds of the cattle genome.

The patent, first written in 2003 and filed in Australia in 2010, describes a method for identifying genetic traits in cattle through the use of genetic markers called SNPs (single nucleotide polymorphisms and pronounced 'snips').

Genomic testing is increasingly used in the livestock sector to select animals with superior genetic traits (tender meat, better milk production).

(ABC News: Roxanne Taylor)

Genomic testing is increasingly used in the livestock sector to select animals with superior genetic traits (tender meat, better milk production).

It identifies 2,510 specific SNPs (there are billions through the genome), but it also lays claims to a large region (500,000 base pairs of DNA) either side of each of the 2,510 identified SNPs.

Much of the concern about the patent comes from the secondary claim because, although the field of genetics has advanced rapidly since 2003, and many millions more SNPs have been located since then, researchers believe their current work could still infringe on the patent.

This is because it includes the 500,000 base pairs of DNA either side of the SNPs actually identified in the patent.

"If this patent was concerned with human genes, there would be a public outcry," MLA's senior council Katrina Howard SC told the court.

"There's no good reason it should apply to cattle."

While MLA attacked the patent on almost every legal ground, a central pillar of its argument was that the method described for identifying the genetic markers was common knowledge before the patent was written in 2003.

They argued that work being done on the human genome, as well as scientific papers published before 2003, meant methods described in the patent was obvious to skilled geneticist.

But Branhaven said that work to map the bovine genome had just started, and was not finished until 2009 so therefore, the patent describes a significant and noteworthy achievement and invention.

No date has been set for a judgement in the matter.

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Federal Court finishes hearing legal argument in controversial cattle genome case - ABC Online

June 7, 2017 by Claudia Lutz Professor of Cell and Developmental Biology Lisa Stubbs leads the Gene Networks in Neural & Developmental Plasticity research theme at the Carl R. Woese Institute for Genomic Biology at the University of Illinois. Credit: Don Hamerman

Mice have a reputation for timidity. Yet when confronted with an unfamiliar peer, a mouse may respond by rearing, chasing, grappling, and bitingand come away with altered sensitivity toward future potential threats.

What changes in the brain of an animal when its behavior is altered by experience? Research at the University of Illinois led by Professor of Cell and Developmental Biology Lisa Stubbs is working toward an answer to this question by focusing on the collective actions of genes. In a recent Genome Research publication, Stubbs and her colleagues identified and documented the activity of networks of genes involved in the response to social stress.

"The goal of this study was to understand the downstream events in mice, and how they are conveyed across interacting brain regions . . . how they might set the stage for emotional learning in response to social threat," said Stubbs. Answers to these questions could help scientists understand how the brains of other animals, including humans, generate social behavior, as well as what goes wrong in disorders of social behavior.

The new results are part of a large-scale research project funded by the Simons Foundation that is headed by Stubbs and includes many of her coauthors, including first authors Michael Saul and Christopher Seward. Stubbs, Saul, Seward, and other coauthors are members of the Carl R. Woese Institute for Genomic Biology (IGB); Saul is an IGB Fellow and Seward is a graduate student.

An aggressive encounter between two mice is just one strand of the web of interactions that connects a population of social animals. Like individuals in a community, the genes in a genome cannot be completely understood until their relationships to one another are examined in context, including how those relationships may change across different tissues and over time.

Stubbs' team wanted to gather information that would allow them to construct this type of comprehensive gene network to reflect how the brain of a social animal responds to an aggressive encounter. They staged a controlled encounter between pairs of mice; one mouse in its home cage, and a second, unfamiliar mouse introduced behind a screen. The presence of the intruder mouse created a social challenge for the resident mouse, while the screen prevented a physical encounter.

The researchers then quantified the activity of genes in several different regions of the brain associated with social behaviorsthe frontal cortex, hypothalamus, and amygdalaand at several time points in the two hours following the encounter. In analyses of the resulting data, they looked for groups of genes acting together. In particular, they sought to identify transcription factors, genes whose protein products help control other genes, that might be orchestrating the brain's molecular response.

Stubbs was excited to discover that the results mirrored and expanded upon previous work in other species by collaborators at the IGB, including work by the laboratory of Director Gene Robinson in honey bees.

"As we examined the regulatory networks active in the mouse brain over time, we could see that some of the same pathways already explicated in honey bees... were also dysregulated similarly by social challenge in mice," she said. "That cross-species concordance is extremely exciting, and opens new doors to experimentation that is not being pursued actively by other research groups."

Among the genes responding to social challenge were many related to metabolism and neurochemical signaling. In general terms, it appeared that cells in the brains of challenged mice may alter the way they consume energy and communicate with one another, changes that could adjust the neural response to future social experiences.

The researchers looked for associations between genes' responses to social experience and their epigenetic state. How different regions of DNA are packaged into the cell (sometimes referred to as chromatin structure) can influence the activity of genes, and so-called epigenetic modifications, changes to this structure, help to modify that activity in different situations.

"We found that the chromatin landscape is profoundly remodeled over a very short time in the brain regions responding to social challenge," said Stubbs. "This is surprising because chromatin profiles are thought to be relatively stable in adult tissues over time." Because such changes are stable, they are sometimes hypothesized to reinforce long-term behavioral responses to experience.

Stubbs and her colleagues hope that by identifying genomic mechanisms of social behavior that are basic enough to be shared even between distantly related animal species, they can discover which biological mechanisms are most central.

"The most exciting thing in my view is using [comparisons between species] to drill through the complex response in a particular species to the 'core' conserved functions," she said, "thereby providing mechanistic hypotheses that we can follow by exploiting the power of genetic models like the mouse."

Explore further: Different species share a 'genetic toolkit' for behavioral traits, study finds

More information: Michael C. Saul et al, Transcriptional regulatory dynamics drive coordinated metabolic and neural response to social challenge in mice, Genome Research (2017). DOI: 10.1101/gr.214221.116

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Social experience tweaks genome function to modify future behavior - Medical Xpress

In a study of 124 patients with advanced breast, lung, and prostate cancers, a new, high-intensity genomic sequencing approach detected circulating tumor DNA at a high rate. In 89% of patients, at least one genetic change detected in the tumor was also detected in the blood. Overall, 627 (73%) genetic changes found in tumor samples were also found in blood samples with this approach.

The study was featured in a press briefing on June 3rd and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

This innovative approach using high-intensity sequencing to detect cancer from circulating tumor DNA in the bloodstream heralds the development of future tests for early cancer detection.

The high-intensity sequencing approach used in this study has a unique combination of breadth and depth. It scans a very broad area of the genome (508 genes and more than two million base pairs or letters of the genome, i.e. A, T, C, and G) with high accuracy (each region of the genome is sequenced or read 60,000 times), yielding about 100 times more data than other sequencing approaches. This enormous amount of data will be instrumental in developing a blood test to detect cancer early.

This approach, however, differs from liquid biopsies, including commercial tests, which only profile a relatively small portion of the genome in patients already diagnosed with cancer for the purpose of helping monitor the disease or detect actionable alterations that can be matched to available drugs or clinical trials.

Our findings show that high-intensity circulating tumor DNA sequencing is possible and may provide invaluable information for clinical decision-making, potentially without any need for tumor tissue samples, said lead study author Pedram Razavi, MD, PhD, a medical oncologist and instructor in medicine at Memorial Sloan Kettering Cancer Center (MSK) in New York, NY. This study is also an important step in the process of developing blood tests for early detection of cancer.

Circulating tumor DNA is a term used to describe the tiny pieces of genetic material that dying cancer cells shed into the blood circulation. To create a picture of the entire genomic landscape of the tumor from circulating tumor DNA, scientists read each tiny fragment and then piece them together as a puzzle. In the bloodstream, circulating tumor DNA is only a small subset of the total cell-free DNA, as most circulating fragments of genetic material come from normal cells.

About the Study

The researchers prospectively collected blood and tissue samples from 161 patients with metastatic breast cancer, non-small-cell lung cancer (NSCLC), or castration-resistant prostate cancer. Thirty-seven patients were excluded due to unavailability of the results of the genetic analysis of the tumor or cell-free DNA samples. For 124 evaluable patients for concordance analysis, researchers compared genetic changes in the tumors to those in circulating tumor DNA from the blood samples.

Tumor tissues were analyzed using MSK-IMPACT, a 410-gene diagnostic test that provides detailed genetic information about a patients cancer. In each blood sample, the researchers separated the plasma, the liquid part of the blood, from the blood cells. The cell-free DNA extracted from the plasma and, separately, the genome of white blood cells were then sequenced using the high-intensity, 508-gene sequencing assay.

Finding tumor DNA in the blood is like looking for a needle in a haystack. For every 100 DNA fragments, only one may come from the tumor, and the rest may come from normal cells, mainly bone marrow cells, said Dr. Razavi. Our combined analysis of cell-free DNA and white blood cell DNA allows for identification of tumor DNA with much higher sensitivity, and deep sequencing also helps us find those rare tumor DNA fragments.

Patients tumors may have various genetic changes; there can be different changes in different parts of the same tumor, as well as in different sites where the tumor spreads in the body. For these reasons, sequencing over very broad regions of the genome is critically important to identify the multitude and diversity of genetic changes in the tumor.

Key Findings

In 89% of patients, at least one genetic change detected in the tumor was also detected in the blood (97% in metastatic breast cancer patients, 85% in those with NSCLC, and 84% in those with metastatic prostate cancer). Overall, including all genomic variations present in most if not all tumor cells (clonal) as well as those present only in subsets of the cancer cells (subclonal) from tumor tissue, the researchers detected a total of 864 genetic changes in tissue samples across the three tumor types, and 627 (73%) of those were also found in the blood.

Importantly, without any prior knowledge from the analysis of tumor tissue, 76% of actionable mutations (genetic changes that can be matched to an approved targeted therapy or one being tested in clinical trials) detected in tissue were also detected in blood.

Prior research in the field has primarily focused on using knowledge from tumor tissue sequencing to identify specific changes to look for in circulating tumor DNA. This approach allows us to detect, with high confidence, changes in circulating tumor DNA across a large part of the genome without information from tumor tissue, said Dr. Razavi. While circulating tumor DNA tests targeting a smaller set of cancer genes are already available for use in routine practice to guide care, by covering a much larger number of cancer genes, this high-intensity sequencing approach may enable development of future tests for early detection of cancer.

Next Steps

The high-intensity sequencing approach used in this study is a research platform and is not intended to be commercially available to patients. To understand the current performance and potential of this assay, the researchers first tested it in advanced cancer, an area where circulating tumor DNA has been previously characterized.

This study will inform development of technology for a future test that could eventually be used as a blood test for early cancer detection. In patients undergoing cancer screening, tumor tissue is not available, and we will need to detect changes in circulating tumor DNA without prior knowledge of tissue analysis results, said Dr. Razavi.

Advantages of Liquid Biopsy Genomic changes can differ between various areas within a tumor, as well as among the different organs where the cancer has spread. A circulating tumor DNA test provides a summary report of all the genomic changes in the primary tumor and metastases. In contrast, a tissue biopsy, which typically takes only a small piece of the tumor, sometimes misses key genetic changes that fuel cancer growth.

Another advantage of liquid biopsy is its ability to capture genomic changes in real time, helping guide treatment planning without the need of additional conventional tissue biopsies. Genomic changes evolve as the cancer grows and spreads. New changes may lead to cancer recurrence or resistance to treatment. A liquid biopsy test requires only a simple blood draw. It is generally safe and convenient to repeat, allowing doctors to keep easier track of new mutations.

This study was funded in part by GRAIL, Inc.

This article has been republished frommaterialsprovided byASCO. Note: material may have been edited for length and content. For further information, please contact the cited source.

The full abstract be be viewed here.

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New Technology Dives Deep Into the Cancer Genome - Technology Networks