Category Archives: Human Genetics

Annunaki, Elohim and Human Genetics: Basis, Bias, or BS? Please Share!
This video covers the HARD SCIENCE behind the properties observed in DNA and various aspects of the Origins of Life. We will cover various concepts of geneti...

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Annunaki, Elohim and Human Genetics: Basis, Bias, or BS? Please Share! - Video

Largest genome-wide study of parasite provides clearest picture yet of genetic changes driving artemisinin resistance

The largest genome-wide association study to date of the malaria parasite Plasmodium falciparum unveils a complex genetic architecture that enables the parasite to develop resistance to our most effective antimalarial drug, artemisinin. The results could help to improve early detection of emerging artemisinin resistance.

The global research collaboration analysed 1612 samples from 15 locations in Southeast Asia and Africa finding 20 mutations in the kelch13 gene, a known artemisinin resistance marker, that appear to work in concert with a set of background mutations in four other genes to support artemisinin resistance.

"Our findings suggest that these background mutations emerged with limited impact on artemisinin resistance -- until mutations occurred in the kelch13 gene," explains Dr Roberto Amato, a first author and Research Associate in Statistical Genomics at the Wellcome Trust Sanger Institute and Oxford University's Wellcome Trust Centre for Human Genetics. "It's similar to what we see with pre-cancerous cells which accumulate genetic changes but only become malignant when they acquire critical driver mutations that kick-off growth."

The variety of kelch13 mutations associated with artemisinin resistance, with new variants continually emerging, makes it difficult to use this gene alone as a marker for genetic surveillance.

Monitoring parasite populations for a specific genetic background - in this case, a fixed set of four well-defined mutations in the fd, arps10, mdr2, and crt genes - could allow researchers to assess the likelihood of new resistance-causing mutations emerging in different locations, helping to target high-risk regions even before resistant parasites take hold.

"We are at a pivotal point for malaria control. While malaria deaths have been halved, this progress is at risk if artemisinin ceases to be effective," says Nick Day, Director of the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand. "We need to use every tool at our disposal to protect this drug. Monitoring parasites for background mutations could provide an early warning system to identify areas at risk for artemisinin resistance."

Researchers also uncovered new clues about how artemisinin resistance has evolved in Southeast Asia. By comparing parasites from Cambodia, Vietnam, Laos, Thailand, Myanmar and Bangladesh, scientists found that the distribution of different kelch13 mutations are localised within relatively well-defined geographical areas.

Whilst artemisinin resistant parasites do appear to have migrated across national borders, this only happened on a limited scale and, in fact, the most widespread kelch13 mutation, C580Y, appeared to have emerged independently on several occasions. Notably parasites along the Thailand-Myanmar border appear to have acquired this mutation separately from those in Cambodia and Vietnam. Crucially, parasite populations in both regions possess the genetic background mutations, even though they are clearly genetically distinct.

There remain many unanswered questions. "We don't yet know the role of these background mutations," says Dr Olivo Miotto, a first author and Senior Informatics Fellow at MORU and the Centre for Genomics and Global Health. "Some may not affect drug resistance directly, but rather provide an environment where drug resistance mutations are tolerated. Since kelch13 has hardly changed in 50 million years of Plasmodium evolution, we can assume that this gene is essential to parasite survival. Therefore, kelch13 mutations may severely handicap mutant parasites, compromising their survival unless some other change can counteract this negative effect."

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Genetics underpinning antimalarial drug resistance revealed

DCDC14 | The Human Genetics Historical Library: collecting for the future
Karen Pierce, Cardiff University Discovering Collections, Discovering Communities 2014 was a collaborative conference hosted by The National Archives and Research Libraries UK, in partnership...

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DCDC14 | The Human Genetics Historical Library: collecting for the future - Video

HOUSTON -- (Jan. 15, 2015) - Alteration of lipid metabolism in brain cells promotes the formation of lipid droplets that presage the loss of neurons, said researchers from Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital in a report that appears online in the journal Cell.

Neuroscience graduate student Lucy Liu, and Dr. Hugo Bellen, professor of molecular and human genetics, neuroscience, a Howard Hughes Medical Institute investigator and director of the Graduate Program in Developmental Biology at Baylor connected the presence of lipid droplet accumulation in the glia of specific mutants as a harbinger of neurodegeneration.

Fruit fly genetics

The Bellen lab uses fruit fly mutants of evolutionarily conserved genes that lead to neurodegeneration in human patients to dissect the molecular mechanisms that underlie the demise of neurons. The fruit flies carry mutations in genes that have human homologs that cause Leigh syndrome, Charcot-Marie-Tooth type 2A2 and ARSAL (autosomal recessive spastic ataxia with leukoencephalopathy). All of these mutations affect the function of the mitochondria, the powerhouse of the cell.

Lipid droplets and energy

Lipid droplets are organelles that serve as energy storage depots. They accumulate in the brain support cells (glia) when defects in the mitochondria of neurons lead to elevated levels of reactive oxygen species (ROS). Working with three independent fruit fly models and a mouse model, Liu et al., revealed a novel pathway leading to this accumulation through the inappropriate activation of two proteins: c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP). These lipid droplets accumulate in glial cells before signs of neurodegeneration appeared.

"This is the first documentation of lipid droplet accumulation in glial cell" said Liu, first author of the study. The authors show that elevated reactive oxygen species in the neurons promotes synthesis of lipids leading to the formation of lipid droplets in glia. This accumulation affects the glia's ability to support the neurons when the lipid droplets become peroxidated, completing a negative feedback loop.

Not enough for neurodegeneration

"ROS or lipid droplets alone do not lead to the rapid onset of neurodegeneration," said Bellen, senior author on the study. "The synergism of ROS with lipid droplets is key. Reducing one or the other delays neurodegeneration."

Upon further investigation, Liu and her colleagues showed that reducing many of the components of this pathway can delay neurodegeneration. For example, treatments with a blood-brain-barrier penetrating antioxidant delay the onset of neurodegeneration in flies and mice developed by their collaborator Dr. Albert Quintana at University of Washington in Seattle.

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Baylor College of Medicine scientist identify a novel precursor to neurodegeneration

Largest study to date of rare genetic variants and asthma risk finds few associations

Despite a strong suspected link between genetics and asthma, commonly found genetic mutations account for only a small part of the risk for developing the disease - a problem known as missing heritability.

Rare and low frequency genetic mutations have been thought to explain missing heritability, but it appears they are unlikely to play a major role, according to a new study led by scientists from the University of Chicago. Analyzing the coding regions of genomes of more than 11,000 individuals, they identified mutations in just three genes that were associated with asthma risk. Each was associated with risk in specific ethnicities. Their findings, published in Nature Communications on Jan. 16, suggest gaps in the current understanding of asthma genetics.

"Previous studies have likely overestimated the heritability of asthma," said study senior author Carole Ober, PhD, Blum-Riese Professor and chair of the Department of Human Genetics at the University of Chicago. "This could be because those estimates are based on correlations between family members that share environment as well as genes, which could inflate the heritability. Gene-environment interactions are not considered in these large scale association studies, and we know that these are particularly important in establishing individual risks for asthma."

Asthma affects more than 25 million adults and children of all ages and ethnicities in the US. Due to the widespread nature of the disease, most studies of its genetic underpinnings have focused on commonly occurring mutations, referred to as genetic variants. However, while numerous such variants have been identified, they are able to account for only a small proportion of the risk for inheriting or developing asthma. Rare mutations, found in less than five percent of the population, have been hypothesized to explain this disparity.

Graduate student Catherine Igartua led the analysis under the supervision of co-senior author Dan Nicolae, PhD, Professor in the Departments of Medicine, Statistics and Human Genetics. She evaluated nearly 33,000 rare or low frequency mutations in more than 11,000 individuals of a variety of ethnicities representing European, African and Latino backgrounds. She analyzed mutations jointly across subjects, using a technique that allowed them to study mutations common in one ethnicity, but rare in others.

Only mutations in the genes GRASP, GSDMB and MTHFR showed a statistical link to asthma risk. Mutations in the first two genes were found primarily in Latino individuals, and mutations in the last gene in those with African ancestry. These genes, involved in protein scaffolding, apoptosis regulation and vitamin B9 metabolism respectively, have as yet unknown roles in asthma. The rarity and ethnic-specificity of these genes is insufficient to account for the widespread prevalence of asthma.

Although rare mutations might not contribute much to population asthma risk, these genes still have the potential to serve as targets for therapeutic development. Ober points to the discovery of rare mutations in the LDL receptor that eventually led to the development of statins to treat high cholesterol. She also notes that it is possible, but unlikely, that there are mutations with large effects on asthma risk outside of their screen as it looked at approximate 60 percent of mutations in coding regions of the genome.

"It was assumed that there would be rare mutations with larger effect sizes than the common variants we have been studying," Ober said. "Surprisingly, we found that low frequency mutations explain only a very small amount of asthma risk."

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Rare mutations do not explain 'missing heritability' in asthma

Software and silicon are sometimes the poor relations of the science world, their advances eclipsed by more glamorous breakthroughs in physics, genetics, and space exploration. Progress in AI and robotics, in particular, is often greeted with as much with trepidation as praise. Yet some amazing leaps were made in 2014 alone, from a robotic hand which an amputee can "feel" to a realistic virtual universe.

Here's our nine best new advances:

In April, electronic artist Squarepusher released an EP called Music for Robots, which was played by actual robots with musical superpowers. The guitarist of Z-machines, Mach, plays two guitars with the aid of 78 fingers and 12 picks. Cosmos triggers notes on his keyboard with lasers and drummer Ashura uses his six arms to wield 21 drumsticks. Z-Machines were created at the University of Tokyo by CGI artist Yoichiro Kawaguchi, robotics engineer Naofumi Yonetsuka, and media artist Kenjiro Matsuo.

Squarepushers objective was to see if robot musicians could play emotionally engaging music. "Part of what interests me is when we listen to a robot, do we listen to it as if we're listening to a human?" he said. "I wasn't trying to make it emulate a human being, but I was trying to make it do something which I wanted to hear. Now the question remains, is the thing which I want to hear a human being?"

Chips inspired by the billions of neurons in the human brain made a splash this year. Current hardware architectures separate computation and storage of information and operate sequentially, limiting the amount of data which can be processed and synthesized. So neuromorphic chips integrate data storage and processing and can operate in parallel, mimicking the way the human brain processes sensory information like images and sound in a massively parallel manner. Such chips could recognize patterns in large amounts of data more efficiently than current linear or "left-brained" architectures.

IBM announced in August that it had packed the largest number of chips ever on to its latest chip, the TrueNorth processor. Powered by a million artificial neurons and 256 million synapses (in the brain a synapse allows electrical charge to pass between neurons) the chip is laid out in a network of 4,096 neurosynaptic cores which integrate memory and computation and operate in parallel in an event-driven fashion. TrueNorth uses a mere 70 milliwatts in operation, giving it a power density (power consumption per cm2) 10,000 lower than most microprocessors. This allows it to efficiently perform power-hungry tasks like detecting and classifying objects in a video stream.

In June, a chatbot program called Eugene Goostman persuaded 33% of human interrogators that it was actually a 13-year-old boy, making it the first piece of software to pass the Turing test. Alan Turing predicted in a 1950 paper that by the year 2000 a computer would play the imitation game well enough that "an average interrogator will not have more than 70% chance of making the right identification after five minutes of questioning." Developers Vladimir Veselov and Eugene Demchenko gave Eugene the personality of a teenage Ukrainian boy in order to make gaps in his knowledge seem more plausible.

In October Australian researchers claimed a quantum computing breakthrough when they created two new types of quantum bit, or "qubit". A bit is always in one of two states0 or 1 while a qubit can be in superpositions, i.e., in both of its possible states at once. Once a qubit is measured, however, it has one known state. A quantum computer maintains a sequence of qubits which can be in every possible combination of 1s and 0s at once, giving it the potential to perform complex calculations exponentially faster than classical computers.

The first type of qubit created by the researchers exploits an atom made of phosphorous, which achieved 99.99% accuracy in quantum operations, while the second relies on an artificial atom made of conventional silicon transistors. Both qubits were housed in a very thin layer of silicon from which magnetic isotopes had been removed to eliminate noise in the quantum calculations. (Quantum states are very fragile and prone to interference, a fact that has proved to be one of the major obstacles to the development of a practical quantum computer.) The team also set a new world record by preserving a quantum state for a full 35 seconds.

In September Akamai announced that the average global Internet connection speed had smashed the 4 megabit-per-second broadband threshold for the first time, hitting 4.6 Mbps during the second quarter of 2014. The global average peak connection speed also increased 20% to 25.4 Mbps between the first and second quarter of 2014.

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9 Things Computers Can Do Now That They Couldn't Do A Year Ago

An international research team finds a link between retinal degeneration and lipid metabolism

IMAGE:Dr. Robert Koenekoop examines a child's eyes and vision at the McGill Ocular Genetics Laboratory. view more

Credit: McGill University Health Centre

This news release is available in French.

Finding genes for retinal degenerations has immediate benefits for people living with blindness and vision loss, their families, and their physicians. Establishing a genetic cause confirms the clinical diagnosis at the molecular level, helps predict the future visual prognosis, suggests therapies, and allows some patients to join clinical trials. While more than 200 genes for retinal degenerations have been identified, approximately 40-50% of cases remain a mystery.

When 11 year old Naomi Lalandec walked into Dr. Robert Koenekoop's clinic at the Montreal Children's Hospital of the McGill University Health Centre (MUHC) with blindness and dwarfism due to Oliver McFarlane Syndrome (OMS), her unknown mutation sparked an international gene hunt. Comparing her genome to others with OMS and Leber congenital amaurosis (LCA), another form of childhood blindness, uncovered a new gene that is critical for vision. What makes this breakthrough exceptional is that it opens up new treatment avenues for OMS and LCA and potentially other retinal degenerative diseases.

"It was like finding a needle in a haystack," said Dr. Koenekoop, who is also a researcher at the Research Institute of the MUHC and a Professor of Human Genetics, Paediatric Surgery and Ophthalmology at McGill University. "It was so obvious to all of us that this was big; a new gene, a possible new disease pathway, a new treatment avenue." With ongoing support from the Foundation Fighting Blindness (FFB), Canada's largest charity supporting vision research, Dr. Koenekoop has spent more than a decade searching for genes linked to blindness. This search brought together an international team of scientists, including Dr. Michel Cayouette at the Institut de recherches cliniques de Montral (IRCM), Dr. Doris Kretzschmar at the Oregon Health and Science University, Dr. Jacek Majewski from the McGill University and Gnome Qubec Innovation Centre and more than 30 others from around the world. Together, the team identified mutations in the PNPLA6 gene in families with retinal degeneration. This is the 20th gene associated with LCA and the first associated with OMS.

Although we've known about the PNLPA6 gene for more than 45 years, no one had identified that mutations in this gene can lead to retinal degeneration - until now. To better understand the role of this gene, the team studied how it functions in fruit flies. They learned that the PNPLA6 gene is expressed and located in photoreceptors (which are the light-sensing cells in the eye) and that mutating the gene causes photoreceptors to die.

To determine what PNPLA6 was doing in photoreceptors, the team did a variety of experiments. They observed that some lipids were elevated in fruit flies with the PNPLA6 mutation, which led them to conclude that PNPLA6 affects phospholipid metabolism. Phospholipids are located in our cell membranes where they influence the membrane's shape and functioning. They also influence how cells communicate with each other by determining the signals that are able to pass through cell membranes. When phospholipids stop doing what they are supposed to do, important signals get lost and cells can no longer maintain their structures or respond to their environment.

This novel insight about the role of phospholipid metabolism in photoreceptor biology paves the way for new sight-saving treatments. These potentially game-changing results were published on January 9, 2015 in the prestigious journal Nature Communications.

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Genetic discovery about childhood blindness paves the way for new treatments

By RTT News, January 12, 2015, 08:18:00 AM EDT

(RTTNews.com) - Seattle Genetics, Inc. ( SGEN ) and Bristol-Myers Squibb Co. ( BMY ) Monday said they have entered into a clinical trial collaboration agreement to evaluate the investigational combination of Seattle Genetics' antibody-drug conjugate, or ADC, Adcetris (brentuximab vedotin) and Bristol-Myers Squibb's immunotherapy Opdivo (nivolumab) in two planned Phase 1/2 clinical trials.

The first trial will evaluate the combination of Adcetris and Opdivo as a potential treatment option for patients with relapsed or refractory Hodgkin lymphoma or HL, and the second trial will focus on patients with relapsed or refractory B-cell and T-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma.

Adcetris is an ADC directed to CD30, a defining marker of classical HL, which combines the targeting ability of a monoclonal antibody with the potency of a cell-killing agent. Opdivo is a human programmed death receptor-1 blocking antibody that binds to the PD-1 receptor expressed on activated T-cells.

The studies are expected to begin in 2015, with Seattle Genetics conducting the HL trial and Bristol-Myers Squibb conducting the NHL trial.

Adcetris is approved in relapsed HL and systemic anaplastic large cell lymphoma, but is not currently approved for the treatment of relapsed, transplant eligible HL or for the treatment of other types of NHL. Opdivo is currently not approved for the treatment of lymphoma.

For comments and feedback: contact editorial@rttnews.com

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Seattle Genetics, Bristol-Myers Report Clinical Trial Collaboration

Human tests of Ebola vaccines 'about to begin' in affected countries: WHO

Geneva (AFP) - Human tests of two possible Ebola vaccines have proven safe and now tests to measure their efficiency will begin within weeks in the three west African countries ravaged by the deadly virus, the World Health Organization said Friday.

"These trials are about to begin for the two lead vaccines," WHO assistant director general Marie-Paule Kieny told reporters, adding that the vaccines would be tested on tens of thousands of people across Guinea, Liberia and Sierra Leone.

The Phase III testing to ensure the vaccines actually provide protection against the virus that has killed 8,259 people in the three African countries is set to begin in Liberia by the end of the month, she said.

Separate tests are scheduled to start in Sierra Leone and Guinea in February, she added.

There is no licensed treatment or vaccine for Ebola, and the WHO has endorsed rushing potential ones through trials in a bid to stem the epidemic.

The two potential vaccines that have been undergoing Phase 1 safety tests on humans are ChAd3, made by Britain's GlaxoSmithKline, and VSV-EBOV, manufactured by the Public Health Agency of Canada and developed by Merck.

Tests of the two potential vaccines have been conducted on volunteers in a range of countries, including Switzerland, Mali, Gabon, Britain, Germany, Canada and the United States.

Both have shown to have "an acceptable safety profile," Kieny said, relaying the findings of a high-level meeting of policy makers, researchers, regulators and vaccine developers in Geneva Thursday.

"That is really good news," she said, acknowledging that "the world is waiting for us to get these vaccines ready and out to the people with this virus raging through their communities."

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Human tests of Ebola vaccines 'about to begin' in affected countries: WHO

Sequencing facility and shared postdoctoral program to support genetic discovery research to advance development of new treatments

CAMBRIDGE, MA, and NEW YORK, NY (January 9, 2015) -- Biogen Idec (NASDAQ: BIIB) and Columbia University Medical Center have formed a $30 million strategic alliance to conduct genetics discovery research on the underlying causes of disease and to identify new treatment approaches. As part of this agreement, a sequencing and analysis facility and shared postdoctoral program will be established at Columbia to support collaborative genetics studies. The agreement will integrate genomics research conducted at Columbia with Biogen Idec's understanding of disease mechanisms and pathways, and expertise in discovering new medicines.

"Our understanding of human genetics is rapidly expanding, and there is growing recognition that the elucidation of the genetic causes of disease will have a transformative effect on both patient care and drug development in many different diseases," said David Goldstein, PhD, founding director of Columbia University's Institute for Genomic Medicine. "This collaboration marries the exceptional drug development expertise of Biogen with cutting-edge genomics expertise at Columbia University Medical Center. It will not only focus on target identification and validation at the early stages of drug development, but also facilitate genetically informed evaluation of treatments."

"Human genetic technologies and analytics have advanced to the point where they are becoming central to the discovery and development of new medicines," said Tim Harris, PhD, DSc, Senior Vice President, Technology and Translational Sciences, Biogen Idec. "We are committed to working with leading institutions such as Columbia to advance basic genetic research and, by combining our unique strengths, accelerating the discovery of potential new treatments."

The collaboration will enable Biogen Idec and Columbia to investigate the genomes of patients showing unusual treatment responses or unique disease presentations and to explore the connections among genes, pathways, and disease processes. The ultimate goal will be to provide multiple qualified targets for new therapeutic approaches, increasing the potential for the development of new treatments.

"This collaboration with Biogen, with its focus on the genetic causes of diseases, fits in perfectly with Columbia's commitment to precision medicine," said Lee Goldman, MD, MPH, Harold and Margaret Hatch Professor of the University and dean of the faculties of health sciences and medicine. "The development of new treatments based on this genetic understanding will have profound effects on clinical practice."

The new facility will have broad genetic research capabilities and the capacity to launch and complete whole-genome sequencing projects rapidly. It will allow for rapid population-scale DNA sequencing across a broad range of disease areas, focusing on diseases with significant unmet clinical need such as amyotrophic lateral sclerosis (ALS) and idiopathic pulmonary fibrosis.

Tom Maniatis, PhD, the Isidore S. Edelman Professor of Biochemistry and chair of the Department of Biochemistry and Molecular Biophysics at Columbia University Medical Center and director of Columbia's university-wide precision medicine initiative, said, "The strong clinical and basic science programs in neurodegenerative diseases at Columbia will significantly benefit from the Columbia/Biogen alliance. We expect that the alliance will dramatically advance our understanding of the genetics of these devastating diseases and ultimately lead to mechanism-based treatments, a key aspect of Columbia's precision-medicine initiative."

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Biogen Idec and Columbia Medical Center to conduct collaborative genetics research