Category Archives: Human Genetics

A bacteria in the gut may could hold the key to slowing down the aging process.

Scientists from Baylor College of Medicine and the University of Texas Health Science Center at Houston have found bacterial genes and compounds that extend the life of and slow down the progression of tumors and the accumulation of amyloid-beta, which is associated with Alzheimers disease.

The scientific community is increasingly aware that our body's interactions with the millions of microbes in our bodies, the microbiome, can influence many of our functions, such as cognitive and metabolic activities and aging, corresponding author Meng Wang, Ph.D., associate professor of molecular and human genetics at Baylor and the Huffington Center On Aging, said in a statement.

In this work we investigated whether the genetic composition of the microbiome might also be important for longevity, she added.

The researchers have identified the genes and compounds in C. elegans, a laboratory worm that is a transparent, simple organism that share essential characteristics with human biology.

The worm only lives two-to-three weeks and feeds on bacteria. However, it does progressively age to develop into an adult, while also reproducing.

We think that C. elegans is a wonderful system in which to study the connection between bacterial genes and aging because we can very fine tune the genetics of microbes and test many genes in the worm in a relatively short time, Wang said. We fed C. elegans each individual mutant bacteria and then looked at the worms' life span.

Of the nearly 4,000 bacterial genes we tested, 29, when deleted, increased the worms' lifespan. Twelve of these bacterial mutants also protected the worms from tumor growth and accumulation of amyloid-beta, a characteristic of Alzheimer's disease in humans.

The researchers then discovered that some of the bacterial mutants increased longevity by acting on some of the worms known processes linked to aging. After providing purified colonic acid to the worms, the researchers found that they lived longer.

Based on these results the researchers believe it is possible to design preparations of bacteria or their compounds that could help slow down the aging process.

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Gut Bacteria Could Impact Aging - R & D Magazine

by Jill Max June 13, 2017

Antonio J. Giraldez, Ph.D., has been appointed chair of the Department of Genetics, effective June 1, 2017. Giraldez is professor of genetics and is affiliated with the Yale Cancer Center and the Yale Stem Cell Center. He was director of graduate studies for the Department of Genetics from 2012 to 2016.

Antonio is an outstanding investigator who has made major advances in our understanding of embryonic development. He is committed to continuing the outstanding academic tradition of the department, said Robert J. Alpern, M.D., dean and Ensign Professor of Medicine.

My goal is to continue our trajectory of basic science discovery and bring the research thats being done in our human genetics core closer to patients, so that we become a destination point for analyzing the genomes of thousands of patients.

Giraldezs research in developmental biology, genetics, genomics, and computational biology delves into deciphering the mechanisms by which a single-cell zygote transforms into a multicellular organism. Using zebrafish as a model system, his major contribution has been to contribute to our understanding of the maternal-to-zygote transitionwhat he terms embryonic pubertythe shift that occurs after the embryo interprets and destroys maternal instructions and activates the code contained in its own genome. He also found that the same stem cell factors that reprogram cells play a key role in activation of the genome after fertilization, a universal step in embryonic development that allows an early embryo to develop into different cell types.

Under his leadership, the Department of Genetics will continue to recruit outstanding faculty as it moves into a more quantitative approach to genetics and developmental biology and seeks to bring new understanding to the function of individual genes, as well as the organization of nuclear architecture into gene function. At the same time, Giraldez is excited about the central role genetics will play in our program in personalized medicine. He is eager to build upon Yales strengths in genomic analysis for clinical diagnosis and to leverage the knowledge gained from clinical data to propel basic science discoveries using model systems.

Last year, Giraldez was named as a Howard Hughes Medical Institute (HHMI) Faculty Scholar, an award that recognizes basic researchers who apply innovative approaches to biological problems that are relevant to human health. In 2014, he won the Vilcek Prize for Creative Promise in Biomedical Sciences. He was named as a Pew Scholar in Biomedical Sciences in 2008 and won the John Kendrew Young Investigator Award from the European Molecular Biology Laboratory in 2007. He has twice been a finalist for the Blavatnik National Award for Young Scientists.

Giraldez obtained his doctoral degree in developmental genetics from the European Molecular Biology Laboratory in Heidelberg, Germany and did postdoctoral training in developmental biology at the Skirball Institute of Biomolecular Medicine at New York University Langone Medical Center and Harvard University.

This article was submitted by John Dent Curtis on June 13, 2017.

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Antonio Giraldez Named Chair of Genetics - Yale News

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The birds of the Galpagos Islands are playing a role in understanding evolution.

When Charles Darwin visited the islands, it was the variety of finch beaks that helped him understand how one species could evolve into many.

The Galpagos cormorants, the only species of cormorant to have lost the ability to fly, have enabled scientists to pin down the genes that led to this species split from other cormorants 2 million years ago.

They are genes that are present in birds, mammals and most animals, including the worm often studied in laboratories: C. elegans. In fact, they are even present in some algae. Their ultimate effect varies, however. In humans and in the cormorants, the genes affect bone growth. But mutations in humans can cause dreadful diseases; in the birds, they caused smaller wings, which were not effective for flight, and a weaker breastbone.

Alejandro Burga, who analyzed the DNA of these and other cormorants with his colleagues, is a researcher in the lab of Leonid Kruglyak, the chairman of human genetics at UCLAs medical school. He said he and Kruglyak were discussing how they might use the increasing power of modern genetics to investigate how new species develop.

On a trip to the Galpagos, Kruglyak viewed cormorants as an ideal subject, partly because of their relatively recent evolution as a species and their obvious difference from all their kin.

Patricia Parker, a behavioral ecologist at the University of Missouri, St. Louis, who studies bird diseases in the Galpagos, provided tissue samples for DNA of the flightless cormorants. She had in her freezer over 200 samples of this bird, Burga said.

He and other researchers found that a gene called Cux1 and some others were involved in the growth of cilia. These whiplike structures on the surface of cells can function in movement in single-celled animals. But in birds and humans, they work like antennas, and one of their jobs is to pick up biochemical signals for bone growth.

The end result of mutations in Cux1 in humans can be terrible diseases, called ciliopathies. In the cormorants, however, the result seems to have been to prematurely stop bone growth in the wings, resulting in the loss of flight, but leaving the birds to thrive in the water and on land.

Without a knowledge of DNA and the tools of modern genomics, Darwin could not have come up with the conclusions of the current study, published in Science.

But he certainly would have had something to say.

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How a Galpagos bird lost the ability to fly - Bend Bulletin

The leading nonprofit organizationscreening Jewish couples for genetic diseases hasmore than doubled its testing capacity.

JScreen, based at the Emory University School of Medicines human genetics department, increased its testing panel from 100 to more than 200 disease genes that could affect a couples future offspring.

Many of these conditions happen in families where theres no known history, JScreen Executive Director Karen Grinzaid said in a phone interview. All of a sudden, a child is born, and theres a genetic problem. There is testing available to give people a heads-up about these things before they have kids.

One in three people of Jewish background unknowingly is a carrier for at least one Jewish genetic disease.

Conditions common in the Jewish population, such as Tay-Sachs, Gaucher disease, thalassemia, mucolipidosis Type IV, spinal muscular atrophy and Fragile X syndrome, are part of the nationwide screening process, andmany others are now included.

Half (the diseases) are common in the Jewish population; the other half are just common in the general population, Grinzaid said. Having this broader screening panel is important because, even though I may think Im 100 percent Ashkenazi, I dont absolutely know my background. Its possible there is other ancestry we dont know about. In addition to that, people have mixed backgrounds or may be in interfaith relationships.

She added, What were looking for are diseases where both parents seem healthy, but they dont know theyre carriers, so if they both pass that gene onto a child, that child will have that condition.

Joining Grinzaid in the interview was Gail Heyman, a member of JScreens advisory board and a carrier of the Fragile X syndromepre-mutation who unknowingly passed on the condition to her son. Its a gene that has impacted our family greatly. Usually when you find a genetic disorder, its alarming.You dont know what to do, but after counseling, you can figure out what to do next.

That counseling sets the JScreenprocess apart, Grinzaid said. There are companies you get a kit from that just mail you results, and you have to figure out on your own what to do and what that all means for you and your family. People need to understand the results and what their options are. We wanted to make that support an integral part of our program.

If families have information, they have choices, Grinzaid said. You can have a conversation with your spouse about what you would or would not do if you were to have an affected child. Our goal is to get to people preconception, as much as possible, so they can make decisions on different reproductive options, such as in vitro fertilization or adoption, and maximize their chances of having a healthy family.

The screening for these diseases is done through DNA found in saliva samples using genetic sequencing technology, and JScreen operates under the direction of aphysician who specializes in genetics.

Another thing, Grinzaidsaid. People dont do it because they dont think its affordable, or maybe their insurance doesnt cover it, or theres a huge deductible. A lot of what we do is from philanthropic dollars, so even if their insurance covers nothing, its the same for everybody. That really helps improve access and encourage people to take advantage of the test, and the expanded screening really opens up the door for more people to participate.

The cost of the test, including counseling, is $149.

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JScreen Doubles List of Tested Genetic Diseases - Atlanta Jewish Times

Keolu Fox. TED2016 Fellows. Photo: Bret Hartman / TED

This post is part of an ongoing series of interviews with the 2017 class of National Geographic Emerging Explorers.

GeneticistKeolu Foxis one of 14 National Geographic Emerging Explorers for 2017. This group is beinghonored for the way its members explore new frontiers and find innovative ways to remedy some of the greatest challenges facing our planet. The 2017 class of Emerging Explorers will be honored at the National Geographic Explorers Festival in Washington, D.C. in June.

Keolugrew up in Hawaii, immersed in thestrong cultural traditions and worldview of his native Hawaiian mother. His father grew up all over Israel and North Africa, and is of general European heritage, and had what Keolu describes as an untraditional education. He passed on that world-wide perspective and exposed the family to a lot of broad ideas early on. Those ideastook an interesting shape as Keolu studied archaeology and genome sciences, and began to formulate a new way of looking at human genetics.

Indigenous people, he realized, hold incredible stories of human adaptation to every environment and social situation on Earth. By empowering them to be more involved in genetic research and analysis, hes hoping to start a new chapter in our understanding of all the richness encoded in human DNA. And ultimately to put it to use for the better health and livelihood of everyone.

What is it that you hope to learn from studying the genomics of native people?

Its not specifically about native people in America or Yakut people in Siberia. While these are all fascinating populations of people, the thing that makes them fascinating for meis natural selection. Theres a treasure trove of information in theirDNAthat could benefit all of humanityand its the responsibility of scientific investigators to ensure that exploration of indigenous peoples genomes benefits that community as well, financially or otherwise.

We should be askingwhat makes people, human beings, extraordinary? What makes these people special? Why are these people adapted to high elevations? There are people from Greenland that have had this specific diet of marine mammals,high fat as well as omega 3. Why are we not seeing cardiovascular disease inthat population?

Why do the Sami people of Finland have protective genetic variation against heart disease? Whatever happens in terms of natural selection that results in that population having this protection could yield treatment for all humanity.

Meanwhile the rest of the field is functioning in a world where 95 percentof clinical trials are in white people. When youre looking at the percentages of genomes that have been sequenced, theyre not sequencing whatI would call the most interesting populations. Its just not happening. But there are real limitations for why its not happening.

Part of it is due to the communities we work with, and when you get a feeling for that you understand why that is.

So does it help that you have recent indigenous heritage of your own?

You are your culture, and you are your experiences. Soif youre trying to gain the trust of communities and you know the music theyre listening to, you can move the right way, you look the right way that certainly helps. You cant look like a scientist, right? You have to belike a human being. You cantbe your classic, traditional western lab-coat-wearing, glasses-wearingscientist. This is a different animal.

So there are very few people that have that skillset. It doesnt mean Im the best scientist in genomics, certainly not. And it doesnt mean Im the most authentic native but I happen to be in the right place at the right time.

Is there a way that this shift can happen more broadly?

You have elite educational institutions that are educating indigenous people and you can pass the torch that way. Thats what enables capacity building. Because then we go into our communities and we think about things in novel ways. We dont think about science the same way because were culturally different. The way we approach science is different.

Science is a cultural thing. As much as we like to imagine it as objective,its like a musical idea. The same central note patterns will take on entirely new colors and dimensions when being exploredby a different culture. Maybe that perspective is becoming more common.

I think weve known that for a long time. This indoctrination-by-academy way of approaching sciencehas been effective, but what is it really yielding? Its certainly not yielding innovation that is powerful for indigenous people. it doesnt enable us to recombine indigenous and western knowledge in novel approaches, solutions, treatments, etc.

As an example, the biggest thing that doctors should do is make people feel comfortable. Why do you need to look at the top of a chart to know your patients name?

So to me, thats a huge problem that science needs to overcome. But you are looking at the next generation of people that are going to occupy those spaces. We have met all the qualifications.

Is it difficult to move comfortably in both the western scienceand indigenous worlds?

One thing thats important here is how connected we are with social media and all that. Did you follow what happened in Hawaii with the whole construction of this giant telescopeon Mauna Kea? It was so interesting. For me, obviously Im a laboratory scientist, but if its at the cost of our community, and its at the cost of our aina [land],then I dont think that we should make decisions like that. Its a conservation sort of question. These are negotiations,and Im not an astrophysicist,but I have to step up on behalf of my community and get flown into this stuff.

The only thing I know how to do is speak from my heart. Keep it real.

When you think of yourself at work, what do you picture?

Its variable. One project will involve shipping resources, negotiating, engaging communities thatI havent met before. Making sure that were being respectful of indigenous peoples values and their culture. And then theres the hardcore science aspect of actually collecting information, making sure people understand what we do.The field stuff is always kind of unpredictable, but probably the most fun thing,I would say.

And then I work on other things where its just beingat work,conducting experimentsand thats just moving clear fluids around and like bro, thats not that exciting.It is exciting when you get results and theres this sort of a-ha moment were youre searching for something and you confirm your hypothesis. Thats a very western approach.Its very cool. And then you have the sort of computational aspect. The loads of frustrating time spent writing code that works. and then you have these miracle moments when it does work. HopefullyI can hire people to do that for me in the future. There are students coming up.

And what is that lab work actually like?

I have a bunch of projects that Im either collaborator on or Im the primary. One of them is leprosy based. Another were using genome editing to actually take variation thats been discovered in diverse populations and sort of copy and replace that into cell lines and then observe its function.

Lets say we find a genetic variant, and we think its involved in influencingsomething importantand its only found in Papua New Guinea or something. Well you can take that and do knock-in variations in human or mouse cells.

Ultimately we want to sequence interesting peopleoutliersbecause they have interesting genomes. And they will allow us to discover interesting things that have a bearing on the way that we understand biology.

How are new technologies helping you with this mission?

Mobile genome sequencing.A lot of times in indigenous communities what we have is what people sometimes call helicopter genomics or vampire genomics. Scientists come, get their data, go back to the lab, make discoveries, make tenure track, get in that new tax bracket, get the new BMW, put their kid in private school, and the cycle continues.

So for me its really important to de-black-box the technology to create transparency about whats going on. With mobile genome sequencing, you can actually bring the hardware to a community and with cloud computation you can actually perform your massively parallel sequence alignment and adaptation on-site, where you want, as long as you can acquire access to the internet (or sometimes you wont even need that to happen).

Its a game changer. It really is a game changer. And it think its going to have a profound bearing on the democratization of genome sequencing and genomic technologies.

Want to become a National Geographic Explorer? Learn how you can apply for a grant from the National Geographic Society.

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National Geographic Emerging Explorer Keolu Fox Uncovers the Hidden Treasures of Human Adaptation - National Geographic

A biology professor at the University of Washington in Seattle believes the stress caused by President Donald Trumps time in office will lead to a permanent change in human genetics.

Peter Ward, a professor who works in the earth and space sciences department of UWs College of the Environment, offered his bizarre prediction to Gizmodo earlier this weekwhen the publication asked a handful of evolutionary biologists, Can superhuman mutants be living among us?

Ward argued that significant traumas like abuse or military combat cancause permanent change to the human genome. He went on to suggest Trumps presidency is akin to those traumas and will have an evolutionary consequence on humanity.

Were finding more and more that, for instance, people who have gone through combat, or women who have been abused when you have these horrendous episodes in life, it causes permanent change, which is then passed on to your kids, he said. These are actual genetic shifts that are taking place within people.

Those shifts, Ward contended, can cause huge evolutionary change.

He added: On a larger scale, the amount of stress that Americans are going through now, because of Trump there is going to be an evolutionary consequence.

Earlier in his statement, the professor also predicted the U.S. military willmanipulate genetics to create some sort of superhuman soldiers.

A soldier whos much harder to bleed to death, or a soldier that doesnt need to drink as much water, or doesnt need to eat for five or six days, or doesnt need to sleep any one of these things would be an enormous advantage in warfare, he said.

This isnt the first time Ward has raised eyebrows for his ideas.

In his 2009 book The Medea Hypothesis: Is Life on Earth Ultimately Self-Destructive? Wardargued that life on earth will cause its own destruction in order to save the planet.

He argued at the time, The Christian Science Monitor reported, that life will self-destruct prematurely, many years before the sun, which he believes will begin to expand in roughly one billion years, burns the biosphere away.

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Biology professor: Trump's presidency will permanently alter human genetics - TheBlaze.com

Fruit flies show some links between genetics and behaviour that are surprisingly similar to those in humans.

Susumu Nishinaga / Getty

Scientists are creeping closer to the genetic mechanisms that underpin schizophrenia and bipolar disorder through inducing aggression in fruit flies.

A team led by Liesbeth Zwarts of Belgiums University of Leuven are studying how altered levels of a protein associated with a gene thought to be linked to mental illness affects behaviour.

In humans, mutations of the gene known as PRODH, situated on chromosome 22, has been associated with the development of schizophrenia, bipolar disorder and some other, rarer, neurological conditions. Its influence has been confirmed in mouse studies, but the precise mechanisms by which it works have remained little understood.

To try to throw some light on the subject, Zwarts and her colleagues looked at the role of an almost identical fruit fly gene, known as slgA.

In a previous study, in 2008, the team had established that neutralising slgA induced aggressive behaviour in fruit flies. Manipulating levels and different proteins expressed by the gene (known as isoforms) thus made for a promising avenue into understanding the functions that underpin the sort of aggression that often typifies mental illness in humans.

Reporting in the journal Disease Models and Mechanisms, the scientists reveal that although slgA is found throughout the fruit fly brain, only the slgA found in an area known as the lateral neurons ventral (LNv) produced aggression when manipulated.

The results suggest that particular behaviours maybe linked to protein components in specific cell types, and that disruption to the metabolism of those specific types may be what catalyses abnormal behaviour.

Interestingly, the lateral neurons ventral are also known to play a key role in regulating circadian rhythms, which determine the sleep/wake cycle in flies and humans both.

Disruption to circadian rhythms has previously been identified as a driver for neurological disorders. However, Zwarts and her colleagues established that changing the activity of the slgA gene did not affect the cells circadian regulation.

Thus, the lateral neurons ventral may affect mental health in at least two although separate ways.

The team plans to continue its investigation, using the fruit fly model to assist in determining why current treatments for neuropsychiatric disorders in humans dont always work.

Once we have demonstrated the direct relevance of our Drosophila models for psychiatric disorders, we aim to pursue drug screens, says team member Patrick Callaerts.

In that sense our work may contribute to defining alternative treatment options.

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Aggro fruit flies may hold genetic keys to human mental illness - Cosmos

According to the textbooks, all humans living today descended from a population that lived in east Africa around 200,000 years ago. This is based on reliable evidence, including genetic analyses of people from around the globe and fossil finds from Ethiopia of human-like skeletal remains from 195,000165,000 years ago.

Now a large scientific team that I was part of has discovered new fossil bones and stone tools that challenge this view. The new studies,published in Nature, push back the origins of our species by 100,000 years and suggest that early humans likely spanned across most of the African continent at the time.

Across the globe and throughout history, humans have been interested in understanding their originsboth biological and cultural. Archaeological excavations and the artefacts they recover shed light on complex behaviourssuch as tool making, symbolically burying the dead or making art. When it comes to understanding our biological origins, there are two primary sources of evidence: fossil bones and teeth. More recently, ancient genetic material such as DNA is also offering important insights.

The findings come from the Moroccan site ofJebel Irhoud, which has been well known since the 1960s for its human fossils and sophisticated stone tools. However, the interpretation of the Irhoud fossils has long been complicated by persistent uncertainties surrounding their geological age. In 2004, evolutionary anthropologistsJean-Jacques Hublin andAbdelouahed Ben-Ncerbegan a new excavation project there. They recovered stone tools and newHomo sapiensfossils from at least five individualsprimarily pieces of skull, jaw, teeth and some limb bones.

To provide a precise date for these finds, geochronologists on the team used athermoluminescence dating methodon the stone tools found at the site. When ancient tools are buried, radiation begins to accumulate from the surrounding sediments. Whey they are heated, this radiation is removed. We can therefore measure accumulated radiation to determine how long ago the tools were buried. This analysis indicated that the tools were about 315,000 years old, give or take 34,000 years.

Researchers also appliedelectron spin resonance dating, which is a similar technique but in this case the measurements are made on teeth. Using data on the radiation dose, the age of one tooth in one of the human jaws was estimated to be 286,000 years old, with a margin of error of 32,000 years. Taken together, these methods indicate thatHomo Sapiensmodern humanslived in the far northwestern corner of the African continent much earlier than previously known.

But how can one be sure that these fossils belonged to a member of our species rather than some older ancestor? To address this question, the anatomists on the team used high-resolutioncomputed tomography(CAT scans) to produce detailed digital copies of the precious and fragile fossils.

They then used virtual techniques to reconstruct the face, brain case and lower jaw of this groupand applied sophisticated measurement techniques to determine that these fossils possessed modern human-like facial morphology. In this way, they could be distinguished from all other fossil human species known to be in Africa at the time.

The high-resolution scans were also used to analyse hidden structures within the tooth crowns, as well as the size and shape of the tooth roots hidden within the jaws. These analyses, which were the focus of my contribution, revealed a number of dental characteristics that are similar to other early fossil modern humans.

And although more primitive than the teeth of modern humans today, they are indeed clearly different from, for example,Homo heidelbergensisandHomo neanderthalensis. The discovery and scientific analyses confirm the importance of Jebel Irhoud as the oldest site documenting an early stage of the origin of our species.

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As a palaeoanthropologist who focuses on the study of fossil bones and teeth, I am often asked why we dont simply address thesequestions of human origins using genetic analyses. There are two main reasons for this. Although incredibly exciting advances have been made in the recovery and analysis of genetic material from fossils that are several hundreds of thousands of years old, it seems that this is only likely to be possible under particular (and unfortunately rare) conditions of burial and fossilisation, such as a low and stable temperature.

That means there are fossils we may never be able to get genetic data from and we must rely on analyses of their morphology, as we do for other very interesting questions related to the earliest periods of human evolutionary history.

Also, understanding the genetic basis of our anatomy only tells us a small part of what it means to be human. Understanding, for example, how behaviour during our lives can alter the external and internal structure of hand bones can help reveal how we used our hands to make tools. Similarly, measuring the chemical composition and the cellular structure of our teeth can tell us what we were eating and our rate of development during childhood. It is these types of factors that help us really understand in what ways you and I are both similar and different to the first members of our species.

And of course, we should not forget that it is the archaeological record that is identifying when we started to make art, adorn our bodies with jewellery, make sophisticated tools and access a diverse range of plant and animal resources. There have been some intriguing suggestions that human species even older thanHomo sapiensmay have displayed some of these amazing behaviours.

More such research will reveal how unique we actually are in the evolutionary history of our lineage. So lets encourage a new generation of young scientists to go in search of new fossils and archaeological discoveries that will finally help us crack the puzzle of human evolution once and for all.

Matthew Skinner, Senior Lecturer in Evolutionary Anthropology, University of Kent

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We Need Genetics and Anthropology to Solve the Mysteries of Human Origins - Smithsonian

A biology professor has claimed that the mass trauma of Donald Trumps presidency will bring about permanent changes to the human genome.

Peter Ward, an academic at the University of Washington, predicted an evolutionary consequence because of the stress Trumps term in the White House is causing the American population.

He asserted that the process by which human genetics could change is analogous to post-traumatic stress disorder in soldiers or the the victims of domestic abuse.

The unconventional view came in a discussion of human capacity to mutate with the science blog (andGawker offshott)Gizmodo.

Ward was one of seven academics asked to bring their expertise to bear on the question of whether and how X-Men-stylesuperhuman mutants could develop.

After speculating about using gene therapy to develop super-soldiers, Ward went on to posit that permanent genetic changes canoccur as a result of horrendous episodes people go through.

He was not asked about Trump, but brought him up as an example, alongside combat trauma and violence at home:

Were finding more and more that, for instance, people who have gone through combat, or women who have been abusedwhen you have these horrendous episodes in life, it causes permanent change, which is then passed on to your kids. These are actual genetic shifts that are taking place within people. Its called epigenetics, and that too can cause huge evolutionary change.

On a larger scale, the amount of stress that Americans are going through now, because of Trumpthere is going to be an evolutionary consequence.

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Biology Professor: Trump Presidency Is So Traumatic It Will Change Human Genome Forever - Heat Street

June 7, 2017

The mouse lemurthe world's smallest primatehas the potential to transform the field of genetics and serve as an ideal model for a wide range of primate biology, behavior and medicine, including cardiovascular disease and Alzheimer's disease, Stanford University School of Medicine researchers say.

For decades, scientists have relied on mice, fruit flies and worms as genetic models, but despite all their success, these organisms routinely fail to mimic many aspects of primate biology, including many human diseases, said Mark Krasnow, MD, PhD, professor of biochemistry.

Frustrated by the lack of a good study model, Krasnow and his colleagues turned to the mouse lemur and began conducting detailed physiologic and genetic studies on hundreds of these petite, docile creatures in the rainforests of Madagascar.

Working in a Stanford-funded lab on the island country, the scientists report that they already have identified more than 20 individual lemurs with unique genetic traits, including obesity, high cholesterol, high blood sugar, cardiac arrhythmias, progressive eye disease and motor and personality disorders. Their hope is that continued study of these abundant primates could lead to a better understanding, and possibly better treatments, of these and other conditions in lemurs and humans.

'Huge potential'

"I think mouse lemurs have great potential for our understanding of primate biology, behavior and conservation, in the same way that fruit flies and mice over the last 30 or 40 years have transformed our understanding of developmental biology and many other areas of biology and medicine," Krasnow said. "Some of the most fascinating and important questions that need to be answered are primate-specific. For those, we really need something besides humans to complement the work that has been done in fruit flies and mice."

A paper describing the researchers' findings will be published online June 9 in Genetics. Krasnow is the senior author. Lead authorship is shared by graduate student Camille Ezran and postdoctoral scholar Caitlin Karanewsky.

The project began in 2009 when Krasnow, frustrated by the lack of a good animal model for lung diseasehis area of expertisecommissioned three high school interns to search the animal world for something better. By the end of the summer, the interns had come up with the mouse lemur, which fits all the necessary criteria: Like mice, these animals are small (about twice the size of a mouse), develop quickly, reproduce rapidly, produce many offspring, and are inexpensive and easy to maintain and manage. In genetic terms, the mouse lemur is about midway between humans and mice, Krasnow said.

"When I talk to scientists, their faces light up when I tell them about mouse lemurs because they are about the size of a mouse but they are primates, so that makes a huge difference," said Ezran, who was one of the high school interns. "I think they really do present such great potential for biological, behavioral and medical research in general."

Early on in the project, Krasnow sought out the perspective of Stanford veterinarians, ultimately recruiting Megan Albertelli, DVM, PhD, assistant professor of comparative medicine. A geneticist and primate specialist, Albertelli said she was initially skeptical of the idea of lemurs as animal models, but soon became enthusiastic after realizing their enormous potential for contributions in understanding neurologic problems, eye disease and other conditions where mouse models have fallen short.

Trip to France

She accompanied the group on a trip to France to visit with scientists who had been studying lemurs in the laboratory for years. A French team had found that some aging lemurs develop a form of dementia and accumulate plaques in the brain that resemble those of Alzheimer's patients.

"I saw that they were promising models for Alzheimer's disease," Albertelli said. "Alzheimer's is a condition that is hard to model in other animal species, so that was very exciting."

Mouse lemurs live exclusively on Madagascar, where they are found in great abundance. Tens of millions of them populate the island. While lemurs generally are endangered due to habitat destruction, mouse lemurs are not under threat and freely roam the island, said Ezran, who calls them the "rodents of Madagascar."

The Stanford researchers began to develop collaborations with other scientists studying lemurs, including those at the Centre ValBio near the Ranomafana National Park in Madagascar, who have been examining lemur ecology, family structure and behavior for decades.

During periodic visits to the island, Krasnow and his colleagues learned how to catch brown mouse lemurs in the rainforest just outside the research station, using a tiny banana slice inside a trap as a lure. The scientists then tagged and photographed each animal, gave them a thorough physical examination, analyzed them for behavioral issues and abnormalities and removed a drop of blood for detailed genetic and serum studies. The animals then were released back into the wild so the researchers could follow them over time to see how their environments may influence their progress and health. In 2013, Stanford built a sophisticated molecular biology and genetics lab within the ValBio complex, where these studies could be carried out.

'Distinctive personalities'

Lemurs have distinctive personalities, Krasnow said, and the researchers gave each one a name, based on his or her looks or behavior. For instance, one was named Feisty for his unusually aggressive nature; most lemurs are docile.

The work has led to a whole new way of doing genetic studies, said Krasnow, who is also a Howard Hughes Medical Institute investigator. Instead of using the traditional method of introducing genetic mutations into mice to create "knockout" miceor animals with customized genesthey found they were able to find naturally occurring variants among animals in the wild. Moreover, in working with lemurs in their native habitats, the researchers could better understand how the animals interact with their surroundings and the relationship between genes and the environment.

"Instead of introducing mutations in mice or fruit flies, we are doing something much more similar to what is done in humans," he said. "We are looking at all the wonderful genetic variation already existing in nature, since there are so many millions of mouse lemurs out there. We calculate that most 'knockout' mutations are already present in nature, and all we have to do is find them. And because the cost of sequencing a genome is rapidly dropping, it's now possible to sequence the genomes of thousands of mouse lemurs to see what mutations they are carrying."

In doing so, the researchers could accomplish in a few years for a tiny fraction of the cost what the International Knockout Mouse Consortium will accomplish in 10 years, at a cost of nearly $1 billion, he said.

But the project could use some additional staff, as the process of capturing the animals and screening them in the laboratory is labor-intensive, he said. He and his colleagues have come up with a multipurpose solution that will contribute to the local educational system while helping preserve the lemur populations in Madagascar, whose habitats are threatened by farming, mining and logging interests, he said.

Help from students

The group is developing a science curriculum for use in Malagasy high schools in which students learn about biology by exploring the rich environment right outside their school houses. Among the instructors is Manu Prakash, PhD, assistant professor of bioengineering at Stanford and a pioneer in the field of "frugal science," who has brought his powerful $1 paper microscopes to Madagascar and taught students how to explore the microscopic world in which they live, including the lice in their hair, the pathogens in their water and the disease-causing parasites in their environment. The curriculum was first introduced among university students, some of whom now are screening lemurs at the Stanford lab in Madagascar.

"We saw this as an opportunity because we are going over there to study the unique animals and biology and ecology of Madagascar, which is unsurpassed in the world," Krasnow said. "It is the No. 1 hotspot for biodiversity, but most of the students don't realize what they have in their backyards because they are being taught from textbooks and from teachers who have learned from Europeans."

He said the researchers hope to expand scientific curricula at all levels of education, helping train the Malagasy scientists of the future and build scientific capacity in the country, all the while creating an appreciation among the local population of the need to understand and preserve lemurs and other species for the future.

"We are trying to do this in a way that is respectful and will help the lemurs and the people of Madagascar, while enlightening many aspects of primate biology and human disease," he said.

The researchers plan to make the genetic sequencing and phenotyping information they obtain from the lemurs publicly available so that researchers around the world can take advantage of this trove of knowledge, Albertelli said.

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Mouse lemur could serve as ideal model for primate biology and human disease - Phys.Org