Archive for the ‘Gene Therapy Research’ Category

2014 Pediatrics Genetics Video Excerpt
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Alexion Pharmaceuticals, the highly successful biotech company headquartered in Cheshire, will pay a Cambridge-based biotech firm $100 million so it can develop and commercialize drugs that come from 10 of the smaller company's gene therapy research programs.

Alexion, which had $910 million in cash on hand at the end of the third quarter, is receiving tens of millions in state subsidies through the First Five Program. The package includes a $6 million grant from the state, a subsidized $20 million loan that will be made into a gift if Alexion has 650 workers in Connecticut by 2017, and tax credits that could be worth as much as $25 million.

In the first year after the deal, the company added more than 50 workers in the state, and said it had more than 400 employees in August. A spokesman did not return calls for comment Monday.

In addition to the $100 million payment to Moderna Therapeutics announced Monday, Alexion bought $25 million in preferred stock in the company. It promised to make more payments if the drug development hits milestones of success and sales and will pay royalties on future sales.

Moderna specializes in personalized medicine. Alexion specializes in drugs for ultra-rare diseases with no effective treatments.

Alexion has a market cap of $25.6 billion.

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Alexion Invests $125 Million in Cambridge Biotech Company

With the highest-profile seller of $99 genetic tests under fire, will public trust in personalised medicine suffer, an ethicist wonders

IT'S 2008. The New Yorker is chronicling a celebrity "spit party", at which notables nicknamed the "Spitterati" eject saliva into tubes to find out their risk of developing illnesses such as diabetes, heart disease and cancer. The firm involved is 23andMe, a direct-to-consumer genetic testing company whose service was named Invention of the Year by Time magazine.

Fast-forward five years. 23andMe receives a demand from the US Food and Drug Administration (FDA) to stop selling its health-related tests pending scientific analysis. In a separate event, a Californian woman, Lisa Casey, files a $5 million class action lawsuit alleging false and misleading advertising. 23andMe suspends sales of its test, putting paid to its target of reaching 1 million customers by the end of 2013. Where did it all go wrong?

In November, after what the FDA describes as years of "diligently working to help [23andMe] comply with regulatory requirements", the agency sent a scathing letter to the firm's CEO Anne Wojcicki. It stated that 23andMe's Personal Genome Service was marketed without approval and broke federal law, since six years after it began selling the kits, the firm still hasn't proved that they work.

Doubts go back a long way. In the year of the spit party, the American Society for Clinical Oncology commissioned a report that concluded the partial type of analysis involved wasn't clinically proven to be effective in cancer care. In 2010 the US Government Accountability Office concluded that "direct-to-consumer genetic tests [involve] misleading test results... further complicated by deceptive marketing".

What 23andMe offered was a $99 test for 250 genetically linked conditions, based on a partial reading of single-nucleotide polymorphisms (SNPs). These are points where the genomes of different individuals vary by a single DNA base pair. There are some 3 billion base pairs in the human genome this test targets only a fraction of them. Different companies sample different SNPs and so return different results for the same person.

To illustrate this point, in his book Experimental Man, science writer David Ewing Duncan recalled how he received three conflicting assessments of heart attack risk from three different companies. The director of one, deCODEme no longer offering such tests telephoned him from Iceland to urge him to start taking cholesterol-lowering statins. Yet the other two tests one from 23andMe, one from Navigenics, which no longer offers consumer tests had rated him at medium or low risk. Given that some statins carry side effects such as muscle weakness, Duncan might have been ill-advised to follow deCODE's urgent advice.

This is the root of the FDA's concerns. In its letter to 23andMe, it raised the risk that customers could get false information that leads to drastic and misguided medical steps. Wojcicki now says: "We want to work with [the FDA], and we will work with them." But is it too little, too late?

And what of the class action lawsuit, brought by Casey after buying a test? It focuses on the test's accuracy but goes further, targeting what Casey's attorney calls "a very thinly disguised way of getting people to pay [23andMe] to build a DNA database".

By asking customers to fill in surveys about health and lifestyle, 23andMe has been creating a valuable "biobank" for patenting purposes and industry collaboration. The firm has always sought customer consent for use of identifiable data and hasn't disguised its aim. "The long game here is not to make money selling kits, although the kits are essential to get the base level data," says 23andMe board member Patrick Chung. "Once you have the data, [23andMe]... becomes the Google of personalised healthcare."

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Testing times for the consumer genetics revolution

Alnylam Pharmaceuticals Inc. ( ALNY ) provided an update on its pipeline and its goals for the coming years. The company has progressed well with its 'Alnylam 5x15' program so far, and expects six to seven genetic medicine programs in the clinic by 2015 instead of five genetic medicine programs.

One of the important candidates under Alnylam's 'Alnylam 5x15' program is patisiran (ALN-TTR02), which is being developed for the treatment of transthyretin-mediated amyloidosis (ATTR).

The candidate is currently in the phase III APOLLO study in ATTR patients suffering from familial amyloidotic polyneuropathy (FAP). Patisiran is also in a phase II open-label extension study for the treatment of patients suffering from FAP. Alnylam intends to report data from the open-label extension study once a year with initial data expected later this year.

ALN-TTRsc, another important candidate under Alnylam's 'Alnylam 5x15' program is currently in a phase II study in ATTR patients suffering from familial amyloidotic cardiomyopathy (FAC) or senile systemic amyloidosis (SSA). Results from the phase II study are expected late in the year.

Patients successfully completing the phase II study will be eligible for an open-label extension study which is expected to be initiated in mid-2014. Moreover, Alnylam has plans to initiate a phase III study on ALN-TTRsc in patients suffering from TTR cardiac amyloidosis by year end.

Apart from these candidates, Alnylam also has plans to initiate a phase I study on ALN-AT3 (hemophilia and other rare bleeding disorders) soon with initial results expected by year end. Additionally, the company will file three Investigational New Drug (IND) applications by 2015 for ALN-CC5 (complement-mediated diseases), ALN-AS1 (hepatic porphyrias) and ALN-PCSsc for (hypercholesterolemia). We expect investor focus remain on the Alnylam's pipeline going forward.

Alnylam also said that it will acquire Merck & Co. Inc. 's ( MRK ) wholly owned subsidiary Sirna Therapeutics, Inc. for $175 million in cash and equity. Merck is also expected to receive up to $105 million as developmental and sales milestone payments per product along with single-digit royalties related to certain pre-clinical candidates discovered by Merck. Alnylam will also pay $10 million as milestone payments and single-digit royalties for products covered by Sirna's patent estate.

Moreover, Alnylam has expanded its strategic agreement with Sanofi ( SNY ) for the development and commercialization of candidates for the treatment of rare genetic diseases. As per the new agreement, Alnylam will retain most of the product rights in North America and Western Europe whereas Sanofi will become a major Alnylam shareholder with a stake of approximately 12% for an investment of $700 million.

Alnylam's collaborations with big companies like Merck and Sanofi are encouraging. The deals will not help Alnylam to generate revenues from royalties but it will also take its RNAi technology outside its core focus area.

Alnylam presently carries a Zacks Rank #4 (Sell). Some better-ranked stocks include Actelion Ltd. ( ALIOF ) with a Zacks Rank #1 (Strong Buy).

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Pipeline Update at Alnylam - Analyst Blog

PUBLIC RELEASE DATE:

13-Jan-2014

Contact: Haley Bridger hbridger@broadinstitute.org 617-714-7968 Broad Institute of MIT and Harvard

The most comprehensive genetic study to date of the blood cancer multiple myeloma has revealed that the genetic landscape of the disease may be more complicated than previously thought. Through results published in Cancer Cell today, a team of Broad researchers has shown that an individual patient's tumor can harbor populations of cancer cells equipped with different mutations. These findings could have therapeutic implications for patients in the future.

"What this new work shows us is that when we treat an individual patient with multiple myeloma, it's possible that we're not just looking at one disease, but at many in the same person, there could be cancer cells with different genetic make-ups," said co-senior author Todd Golub, the Broad Institute's Chief Scientific Officer and Charles A. Dana Investigator in Human Cancer Genetics at the Dana-Farber Cancer Institute. Golub is also a professor at Harvard Medical School and an investigator at Howard Hughes Medical Institute. "These findings indicate a need to identify the extent of genetic diversity within a tumor as we move toward precision cancer medicine and genome-based diagnostics."

In a detailed study of samples from more than 200 multiple myeloma patients, Golub and colleagues identified frequent mutations in several key genes known to play an important role in cancer including KRAS, NRAS, and BRAF. But they found that many of these telltale mutations were not present in all cancer cells within a tumor instead, they were often found in only a smaller fraction of cells, known as a subclonal population.

Many promising cancer therapies used in treatment today target a specific genetic mutation. This new work suggests that such targeted therapies may have limitations in patients whose tumors are made up of these subclonal populations.

The research team performed follow-up experiments in the lab to explore some of the therapeutic implications, looking specifically at BRAF, a cancer gene for which several inhibitors, or drugs, exist. Previous studies indicated that around four percent of multiple myeloma patients may have mutations in this gene, and a recent report on a single multiple myeloma patient treated with drugs targeting BRAF showed promising results. BRAF inhibitors have also been used to treat patients with melanoma and other forms of cancer. In the lab, however, the research team found evidence that treating a tumor harboring subclonal BRAF mutations with one of these targeted drugs may at best kill a fraction of the cells, and at worst, stimulate another cancer cell subpopulation to grow.

"There's clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others," said co-first author Jens Lohr an associated scientist at the Broad and a medical oncologist at Dana-Farber. "If a patient has a BRAF mutation in less than 100 percent of his cells, or if he has mutations in KRAS or NRAS at the same time may influence the response to an inhibitor."

Resistance or the ability for tumors to shrink and then grow back has become a major hurdle in treating patients with targeted therapies such as BRAF inhibitors. The new research suggests that subclonal populations could be one of the potential reasons many patients suffer relapse after treatment.

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Multiple myeloma study uncovers genetic diversity within tumors

Genetics and Mesothelioma Dr Michele Carbone | Mesothelioma Resources Insurance
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Intro. to Genetics and Evolution: First Hangout
Join the TAs Keri and John as they discuss with students the Week 1 material: Evolution and Mendelian Genetics. Live Broadcast starts at 5:00 pm EST, Wed Ja...

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13-Jan-2014

Contact: Mary Martialay martim12@rpi.edu 518-276-2146 Rensselaer Polytechnic Institute

Troy, N.Y. A team including researchers from Rensselaer Polytechnic Institute have discovered that a specific gene may play a major role in the development of a life-threatening birth defect called congenital diaphragmatic hernia, or CDH, which affects approximately one out of every 3,000 live births.

The hallmark of CDH is a rupture of the diaphragm that allows organs found in the lower abdomen, such as the liver, spleen, and intestines, to push their way into the chest cavity. The invading organs crowd the limited space and can lead to abnormal lung and heart development or poor heart and lung function, which, depending on the severity of the condition, can cause disability or death.

In a paper published recently in the Journal of Clinical Investigation, lead authors at the University of Georgia, along with colleagues from the Rensselaer and the University of California at San Diego, demonstrated for the first time that the gene NDST1 plays a significant role in the proper development of the diaphragm, and that abnormal expression of the gene could lead to CDH.

"We now have a really good picture of this abnormality in mice, and we suspect it is very similar in humans," said Fuming Zhang, a research professor in the laboratory of Robert J. Linhardt, the Ann and John H. Broadbent Jr '59 Senior Constellation Professor of Biocatalysis and Metabolic Engineering, and a member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer. "What this gives us is a total view, from the genetic level, to the molecular level, to the cellular or tissue level, to something that a physician would see a hernia in a newborn."

The discovery began with the observation that mice bred without the NDST1 gene, which produces the eponymous NDST1 enzyme, are more likely to develop CDH than ordinary mice. The enzyme NDST1 is one of four isoforms a group of molecules that are chemically similar, but show subtle functional differences. In mice lacking the NDST1 gene, and therefore the NDST1 enzyme, nature substitutes with an NDST1 isoform (NDST2, NDST3, and NDST4), but the results like substitutions in cooking are noticeable.

In the absence of NDST1, blood vessels supplying the developing diaphragm muscles formed inconsistently, leading to weak points in the muscle tissues that make them prone to hernia. Researchers knew that the NDST1 enzyme is involved in the synthesis of heparan sulfate, so the group turned to the Linhardt's research team at Rensselaer experts in heparan sulfate and glycosaminoglycan analysis to pinpoint the biochemical basis for the abnormality.

"There are two molecules in the interaction that leads to proper blood vessel formation in the diaphragm NDST1 biosynthesized heparan sulfate and the protein SLIT3," said Zhang. "In order for those interactions to be successful, and for blood vessels to form properly, everything must be accomplished within a specific time frame and having a specific structure. We were able to investigate the interactions between the two."

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Congenital diaphragmatic hernia traced from genetic roots to physical defect

POSTED: 01:30 a.m. HST, Jan 12, 2014 LAST UPDATED: 01:55 a.m. HST, Jan 12, 2014

NEW YORK TIMES

KONA From the moment the bill to ban genetically engineered crops on Hawaii island was introduced in May, it garnered more vocal support than any the County Council here had ever considered, even the perennially popular bids to decriminalize marijuana.

Public hearings were dominated by recitations of the ills often attributed to genetically modified organisms, or GMOs: cancer in rats, a rise in childhood allergies, out-of-control superweeds, genetic contamination, overuse of pesticides, the disappearance of butterflies and bees.

Like some others on the nine-member council, Greggor Ilagan was not even sure at the outset of the debate exactly what genetically modified organisms were: living things whose DNA has been altered, often with the addition of a gene from a distant species, to produce a desired trait. But he could see why almost all of his colleagues had been persuaded of the virtue of turning the island into what the bill's proponents called a "GMO-free oasis."

"You just type 'GMO' and everything you see is negative," he told his staff. Opposing the ban also seemed likely to ruin anyone's re-election prospects.

Yet doubts nagged at the councilman, who was serving his first two-year term. The island's papaya farmers said that an engineered variety had saved their fruit from a devastating disease. A study purporting that a diet of GMO corn caused tumors in rats, mentioned often by the ban's supporters, turned out to have been thoroughly debunked.

And University of Hawaii biologists urged the council to consider the global scientific consensus, which holds that existing genetically engineered crops are no riskier than others, and have provided some tangible benefits.

"Are we going to just ignore them?" Ilagan wondered.

Urged on by Margaret Wille, the ban's sponsor, who spoke passionately of the need to "act before it's too late," the council declined to form a task force to look into such questions before its November vote. But Ilagan, 27, sought answers on his own. In the process, he found himself, like so many public and business leaders worldwide, wrestling with a subject in which popular beliefs often do not reflect scientific evidence.

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Effort to demystify GMOs was tough

Current ratings for: Rare genetic mutation confirmed as a cause of Tourette Syndrome

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Brain researchers say they have confirmed for the first time that a rare genetic mutation can cause some cases of Tourette syndrome, with the fault disrupting production of histamine in the brain.

The New Haven, CT, researchers at the Yale School of Medicine say the histamine effect "is a cause of the tics and other abnormalities of Tourette syndrome." Tics are repetitive movements and vocal sounds, and they are unwanted and involuntary - they cannot be controlled.

Publishing their research on mice in the journal Neuron, the authors raise the question of investigating treatment of Tourette syndrome by drugs that target histamine receptors in the brain.

Drugs with such a mode of action are already being explored by pharmaceutical companies for the treatment of separate brain disorders, schizophrenia and ADHD.

Information from the national gene database about histamine describes the chemical's role - it is a messenger molecule released by nerves, among other functions.

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Rare genetic mutation confirmed as a cause of Tourette Syndrome

Advanced Genetics Mod Review- Part 2
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The Slow and Steady Revival of Gene Therapy
The Slow and Steady Revival of Gene Therapy.

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By Steven Reinberg HealthDay Reporter

THURSDAY, Jan. 9, 2014 (HealthDay News) -- A new, preliminary treatment involving triple-gene therapy appears safe and effective in helping to control motor function in Parkinson's disease patients, according to new research.

The therapy, called ProSavin, works by reprogramming brain cells to produce dopamine, the chemical essential for controlling movement, the researchers said. Lack of dopamine causes the tremors, limb stiffness and loss of balance that patients with the neurodegenerative disease suffer.

"We demonstrated that we are able to safely administer genes into the brain of patients and make dopamine, the missing agent in Parkinson's patients," said researcher Kyriacos Mitrophanous, head of research at Oxford BioMedica in England, the company that developed the therapy and funded the study.

ProSavin also helps to smooth out the peaks and valleys often produced by the drug levodopa, the current standard treatment, Mitrophanous said.

The treatment uses a harmless virus to deliver three dopamine-making genes directly to the area of the brain that controls movement, he explained. These genes are able to convert non-dopamine-producing nerve cells into dopamine-producing cells.

Although the study results are promising, the researchers suggest they should be "interpreted with caution" because the perceived benefits fall into the range of "placebo effect" seen with other clinical trials.

Hoping to improve on their results, the researchers have since re-engineered the therapy. "We have a new version which makes more dopamine in patients, and this new version is undergoing safety studies before we initiate trails in patients," he said.

Experts reacted positively but cautiously to the findings, which were published online Jan. 10 in The Lancet. While the treatment seems safe, its potential as a replacement for current therapy still must be proved, they noted.

"The ProSavin study was a positive and important first step for a potential gene therapy for Parkinson's disease," said Dr. Michael Okun, national medical director at the National Parkinson Foundation. "The results of this preliminary study revealed a promising safety profile, and it will be interesting to observe longer-term benefits and how ProSavin will compare to other therapies such as deep brain stimulation."

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Gene therapy may hold promise for advanced Parkinson's disease

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Flight Rising - Dragon Genetics RPG game [LAGGED]
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7-1 Intro to genetics
7-1 Intro to genetics.

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Stem Cell therapy for Cartilage Regeneration in Orthopaedic Surgery
Prof. A A Shetty and Prof. Seok Jung Kim, founders of Shetty - Kim Research Foundation were here at MediCiti to perform 5 stem cell therapy surgeries on 31st...

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Stem Cell therapy for Cartilage Regeneration in Orthopaedic Surgery - Video

VAIL The Vail Symposium hosts Dr. Scott Brandt, Dr. Kristin Comella and Dr. Stan Jones who will lead an interactive discussion on the history, evolution, practical applications and clinical results around stem cell treatments Friday evening in Vail.

The program is part of the Symposiums ongoing Living at Your Peak series, which is dedicated to exploring new breakthroughs in medicine and helping people live healthier, more active lives.

This program fits perfectly with our Living at Your Peak series, said Tracey Flower, the Symposiums executive director. There is a lot surrounding this topic, and has been for quite some time. With recent research in a changing medical industry, it is a great topic to discuss.

An example of breakthroughs in stem cell therapy comes in the form of the record-shattering Broncos quarterback, Peyton Manning. After failed surgeries, Manning traveled to Germany to undergo stem cell treatment on his cervical spine. At 37, Manning is playing his best football.

During this educational program, panelists will discuss the evolution of the stem cell field, explain current procedures, present research and clinical findings, and talk about the potential for stem cell applications in the future.

Join the Vail Symposium at 5 p.m. Friday at the Antlers Hotel in Vail for this event, titled: Stem Cells: The Future of Medicine is Now. Space is limited; reserve your tickets at http://www.vailsymposium.org/calendar or call the Vail Symposium at 970-476-0954.

More about the panelists

Dr. Scott Brandt: Brandt, the medical director of ThriveMD in Edwards, specializes in regenerative and restorative medicine. Brandt completed his undergraduate studies at the University of Michigan at Ann Arbor, and attended medical school at Bowman Gray School of Medicine, Wake Forest University in North Carolina. He then completed his anesthesiology residency training and internship at the University of Illinois and Michael Reese Hospitals in Chicago. As a resident in anesthesiology, Brandt specialized in interventional pain management. Since 1997, this focus has kept him on the leading edge of medical innovations that provide longer lasting solutions for acute and chronic pain. The advancement of stem cell therapy, coupled with Brandts expertise in image-guided injections, has made joint rejuvenation an important part of his practice.

Dr. Kristin Comella: In 2013, Comella was named as one of the 25 most influential people in the stem cell field. She has more than 14 years of experience in regenerative medicine, training and education, research, product development and has served in a number of senior management positions with stem cell related companies. Comella has more than 12 years of cell culturing experience including building and managing the stem cell laboratory at Tulane Universitys Center for Gene Therapy. She has also developed stem cell therapies for osteoarthritis at Osiris Therapeutics. Comella has been a member of the Bioheart senior management team since 2004 and is currently serving as its chief scientific officer.

Dr. Stan Jones: Widely known for performing a ground-breaking stem cell infusion on Governor Rick Perry during a spinal surgery in 2011, Jones is a surgeon and stem cell expert. He received his bachelors degree from Texas Tech in Lubbock before earning his medical degree from the University of Texas Southwestern Medical School in Dallas. Jones continued his medical training at the University of Utah Medical School in Salt Lake City and a residency at the University of Texas Medical School at Houston. Jones was awarded a fellowship to study the lower back at Wellseley Hospital in Toronto, Canada. In addition, he served in the U.S. Army Medical Corp as a Captain. He is licensed to practice in the state of Texas and is certified by the American Board of Orthopedic Surgery.

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Current ratings for: Inherited gene copies 'randomly activated,' study suggests

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It is common knowledge that with many illnesses, such as cancer, risk of development is partly determined by family history of the disease. But new research suggests that "random chance" decides if a certain gene copy that is inherited from our mother or father is actually used.

Researchers from the Karolinska Institutet in Sweden and the Ludwig Institute for Cancer Research in the UK say that their findings, published in the journal Science, may explain why some people become ill even if they have the same gene copy as healthy relatives.

The investigators explain that there are two copies of each gene in the human body - one which is inherited from our mother and one from our father.

They note that the majority of existing research suggests that both gene copies are used equally, but their new study suggests otherwise.

To reach their findings, the researchers created a technique which allowed them to closely analyze how genes work in individual cells - something lead author Dr. Rickard Sandberg says has not been done before.

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Inherited gene copies 'randomly activated,' study suggests

2014 1 3 ZOC Eating Genetic Engineering
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Fewer than 250 adults may be left in West Africa, and those big cats are confined to less than 1 percent of their historic range.

The new study, detailed in the journal PLOS ONE, suggests that without dramatic conservation efforts, three of the four West African lion populations could become extinct in the next five years, with further declines in the one remaining population, study co-author Philipp Henschel, the lion program survey coordinator for Panthera, a global wildcat conservation organization, wrote in an email. [In Photos: The Biggest Lions on Earth]

The majestic lion once roamed throughout West Africa, from Nigeria to Senegal.

But as people have converted wild lands to pastureland, hunted the lion's traditional prey antelopes, gazelles, wildebeest, buffalos and zebras and gotten into conflicts with the animals, the big cat population has plummeted in West Africa.

Cash-strapped West African governments have put little money into lion conservation, in part because "wildlife tourism is quasi-absent in West Africa," Henschel said.

And research institutions have similarly neglected the region.

"Like wildlife tourists, most international research institutions and conservation organizations active in Africa also flock to the iconic game parks in East and southern Africa, meaning that lions faced a silent demise in West Africa over the past decades," Henschel told LiveScience.

Massive Survey

To remedy that, Henschel and his colleagues recently completed a massive, six-year survey of West Africa's lions, using remote cameras, interviews with people and counts of lion tracks. The survey, carried out between October 2006 and May 2012, builds on a smaller study done last year, which found shrinking savannas for lions in the region.

About 400 adult and juvenile lions existed in the region. And the wild cats, which were originally thought to have inhabited 21 separate regions, actually exist in just four. Their range is now confined to pockets in Senegal, Nigeria and the borderlands between Benin, Niger and Burkina Faso.

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Lions Face Extinction in West Africa

USC TREET Seminar Series: Eric Hoffman - Molecular and Clinical Outcome Measures in Rehab Medicine
Eric Hoffman, PhD presents "Molecular and Clinical Outcome Measures in Rehabilitation Medicine: The National Center for Medical Rehabilitation Research in Wa...

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USC TREET Seminar Series: Eric Hoffman - Molecular and Clinical Outcome Measures in Rehab Medicine - Video

Discussion Podcast
Discussion of the paper #39;Development of a Performance of Upper Limb module for Duchenne muscular dystrophy #39;. The contributors in the podcast are as follows: ...

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Jan. 9, 2014 The Fleckvieh is a breed of cattle that originated in the Alpine region. A robust animal, it is now found on every continent, with an estimated worldwide population of around 40 million.

In Germany, there are approximately 1 million Fleckvieh dairy cows: "Their genomes can be traced back to a small number of key ancestors," explains Prof. Ruedi Fries, Chair of Animal Breeding at TUM. "With artificial insemination, male breeding animals can produce more than one hundred thousand offspring."

Infertility caused by a single gene

This practice is fraught with risk, however: If the genetic make-up of any animal contains an unidentified defect, this characteristic will be passed on to future generations. TUM researchers have now discovered that a mutation in the TMEM95 gene on cattle chromosome 19 makes bulls effectively infertile, with a success rate for insemination of less than 2 percent.

"Otherwise, the animals are perfectly healthy and normal," points out Dr. Hubert Pausch, lead author of the study. "The characteristic only manifests itself if bulls inherit the mutation from both the male and female side, i.e. they are homozygous for the defective gene. It is only in this case that the animals should be excluded from breeding." Routine genetic testing for all breeding bulls has been underway since August 2012.

Findings of interest for human medicine

As part of their study, the researchers compared the genome of 40 subfertile animals with 8,000 breeding bulls with normal fertility levels. They discovered that the genetic defect can be traced back to one Fleckvieh animal born in 1966.

The TMEM95 gene encodes a protein on the surface of the sperm heads. The protein probably mediates the binding process between the sperm and egg cells. If it is missing, fertilization will not occur.

"Our findings indicate that genetic defects in TMEM95 could also cause infertility in men," elaborates Pausch. During their investigation of the sperm of infertile breeding bulls, the TUM scientists collaborated with Prof. Sabine Klle and Dr. Matthias Trottmann from Munich's Ludwig Maximilian University. Trottmann helps couples with infertility problems.

Genetic analysis for healthier animals

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Genetic testing to produce more offspring

Gage Green Genetics Pheno Finder
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