Category Archives: Human Genetics

Science Daily

Social phobia: Indication of a genetic cause: Study supports link with ... Science Daily People with social anxiety avoid situations in which they are exposed to judgment by others. Those affected also lead a withdrawn life. Researchers have now ... and more »

Go here to read the rest:
Social phobia: Indication of a genetic cause: Study supports link with ... - Science Daily

March 9, 2017 Credit: University of Oxford

Researchers have for the first time shown that standard tuberculosis (TB) diagnostic tests can be replaced by a sub-24 hour genetic test applied to the TB bacteria in a patient's sputum.

It currently takes up to two months to obtain the full diagnostic information for a patient with TB, as the bacteria grow very slowly in the laboratory. Scientists have sought for years to bypass this time-consuming step by examining the bacterial DNA directly from a sputum sample. However since most of the cells in sputum are human, it is difficult to spot the signal (TB DNA) within the noise (human and other bacteria) and even harder to find a method that might be affordable and practical across the world.

The new process, led by researchers from the University of Oxford and described in the Journal of Clinical Microbiology, rapidly processes the sputum to preferentially retain TB, using simple and relatively affordable materials, and then sequences and analyses the bacterial DNA. The Oxford team worked with researchers from the University of Nottingham, the Foundation for Medical Research, Mumbai, and Public Health England.

Until recently, DNA sequencing has required heavy machines and a well-equipped laboratory, which has limited its potential applications in the field. In this study, researchers have also shown that by using a new, real-time, handheld sequencing device (Oxford Nanopore MInION) they can achieve identical results, but with a process that might be applied anywhere in the world. In one example they achieved an effective turnaround time of 12.5 hours.

By using DNA sequencing, not only does this method detect drug-resistant TB bugs vital information for the patient - but it also enables the tracking the geographical spread of strains, which is hugely valuable to public health workers, and something traditional tests cannot do.

TB is one of the top causes of death by infectious disease in the world, with 10.4 million cases of the disease in 2015, and 1.1 million deaths directly attributable to TB.

Dr Zamin Iqbal from the Wellcome Trust Centre of Human Genetics at Oxford University, who co-led the study, said: 'One of the great challenges with the management of TB is the need for rapid, comprehensive tests that do not require a hi-tech laboratory. We have shown that it is possible to get all information needed both for clinical management and for tracking disease spread, all within 24 hours of taking the sample from the patient. Further, by achieving this with a handheld device, we open the door to in-field diagnostic tests for TB.'

Dr Antonina Votintseva, lead author, said: 'Although genome sequencing has been used increasingly in research for analysing TB, the limiting factor has continued to be the weeks spent culturing the bacteria in the laboratory. By developing an affordable and simple method for extracting M. tuberculosis DNA direct from sputum, and thereby cutting turnaround time to below 24 hours, we have taken a great step towards comprehensive point-of-care diagnosis.

'There is more work to be done of course - our goal is to return test results before the patient leaves their clinic, with huge potential for reducing transmission of the disease, and of drug resistance.'

Dr Stephen Caddick, Wellcome Trust Director of Innovation, said: 'It can take many weeks for conventional tests for TB to provide results. Dr Iqbal and his team have made a significant breakthrough by developing a low-cost DNA extraction method which enables TB whole genome sequencing direct from patient samples and provides results in less than a day. The ability to use this technology to identify bacterial strains that may be resistant to antibiotic treatment, particularly in low and middle income countries, could be invaluable in the fight to tackle drug-resistant infections.'

Explore further: New laptop program can identify drug resistance from bacterial genomes

More information: Antonina A. Votintseva et al. Same-day diagnostic and surveillance data for tuberculosis via whole genome sequencing of direct respiratory samples., Journal of Clinical Microbiology (2017). DOI: 10.1128/JCM.02483-16

Scientists have developed an easy-to-use computer program that can quickly analyse bacterial DNA from a patient's infection and predict which antibiotics will work, and which will fail due to drug resistance. The software ...

The time needed to genetically sequence the bacteria causing tuberculosis (Mtb) from patient samples has been reduced from weeks to days using a new technique developed by a UCL-led team. This could help health service providers ...

Researchers using DNA sequencing to profile antibiotic resistance in infection have achieved a turnaround time from 'sample to answer' of less than four hours for urinary tract infections (UTIs).

Microbes in the gut can "disarm" antibiotics, leading to antibiotic resistance and incurable infections. A new method makes it possible to quickly detect resistance genes and, hence, choose the most efficient type of antibiotic ...

As World TB day (24 March) marks global efforts to eliminate tuberculosis as a public health problem by 2035, Oxford University researchers, in partnership with Public Health England (PHE), will lead a new worldwide collaboration ...

The U.S. medical community needs a better understanding of the biology of pain and how it plays out in individuals to be able to combat the national epidemic of addiction to painkillers, according to researchers from the ...

Leishmaniasis, caused by the bite of a sand fly carrying a Leishmania parasite, infects around a million people a year around the world. Now, making progress toward a vaccine against the parasitic disease, researchers reporting ...

Researchers have for the first time shown that standard tuberculosis (TB) diagnostic tests can be replaced by a sub-24 hour genetic test applied to the TB bacteria in a patient's sputum.

For 130 years, surgery has been the standard treatment for appendicitisinflammation of the appendix, a short tube extending from the colon.

The diagnosis, understanding and management of Crohn's disease may have just received a helping hand from a joint ASU Biodesign Institute and Mayo Clinic study aimed at developing a better blood test for the disease.

Duke scientists have discovered a biomarker of the runaway immune response to infection called sepsis that could improve early diagnosis, prognosis, and treatment to save lives.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Go here to see the original:
Genetic sequencing offers same-day TB testing - Medical Xpress - Medical Xpress

The Rock of Gibraltar appears out of the plane window as an immense limestone monolith sharply rearing up from the base of Spain into the Mediterranean. One of the ancient Pillars of Hercules, it marked the end of the Earth in classical times. Greek sailors didnt go past it. Atlantis, the unknown, lay beyond.

In summer 2016, Gibraltar is in the throes of a 21st-century identity crisis: geographically a part of Spain, politically a part of Britain; now torn, post-Brexit, between its colonial and European Union ties. For such a small area less than seven square kilometres Gibraltar is home to an extraordinarily diverse human population. It has been home to people of all types over the millennia, including early Europeans at the edge of their world, Phoenicians seeking spiritual support before venturing into the Atlantic, and Carthaginians arriving in a new world from Africa.

But Ive come to see who was living here even further back, between 30,000 and 40,000 years ago, when sea levels were much lower and the climate was swinging in and out of ice ages. It was a tough time to be alive and the period saw the species that could, such as birds, migrate south to warmer climes, amid plenty of local extinctions. Among the large mammal species struggling to survive were lions, wolves and at least two types of human: our own modern human ancestors, and the last remaining populations of our cousins, the Neanderthals.

By understanding more about these prehistoric people, we can learn about who we are as a species today. Our ancestors experiences shaped us, and they may still hold answers to some of our current health problems, from diabetes to depression.

Im picked up outside my hotel by archaeologists Clive and Geraldine Finlayson, in a car that itself looks fairly ancient. Typical for this crowded little peninsula, they are of diverse origins he, pale-skinned and sandy-haired, can trace his ancestry back to Scotland; she, olive-skinned and dark-haired, from the Genoese refugees escaping Napoleons purges. How different we humans can look from each other. And yet the people whose home I am about to visit truly were of a different race.

We dont know how many species of humans there have been, how many different races of people, but the evidence suggests that around 600,000 years ago one species emerged in Africa that used fire, made simple tools from stones and animal bones, and hunted big animals in large cooperative groups. And 500,000 years ago, these humans, known as Homo heidelbergensis, began to take advantage of fluctuating climate changes that regularly greened the African continent, and spread into Europe and beyond.

The use of tools could be part of a wider breadth of survival adaptations, including resistance to plague and HIV ( Tom Sewell)

By 300,000 years ago, though, migration into Europe had stopped, perhaps because a severe ice age had created an impenetrable desert across the Sahara, sealing off the Africans from the other tribes. This geographic separation enabled genetic differences to evolve, eventually resulting in different races, although they were still the same species and would prove able to have fertile offspring together. The race left behind in Africa would become Homo sapiens sapiens, or modern humans; those who evolved adaptations to the cooler European north would become Neanderthals, Denisovans and others whom we can now only get a glimpse of with genetics.

Neanderthals were thriving from Siberia to southern Spain by the time a few families of modern humans made it out of Africa around 60,000 years ago. These Africans encountered Neanderthals and, on several occasions, had children with them. We know this because human DNA has been found in the genomes of Neanderthals, and because everyone alive today of European descent including me has some Neanderthal DNA in their genetic makeup. Could it be that their genes, adapted to the northerly environment, provided a selective advantage to our ancestors as well?

After driving through narrow tunnels on a road that skirts the cliff face, we pull up at a military checkpoint. Clive shows the guard our accreditation and were waved through to park inside. Safety helmets on to protect from rockslides, we leave the car and continue on foot under a low rock arch. A series of metal steps leads steeply down the cliff to a narrow shingle beach, 60 metres below. The tide is lapping the pebbles and our feet must negotiate the unstable larger rocks to find a dry path.

Ive been concentrating so hard on keeping my footing that it is something of a shock to look up and suddenly face a gaping absence in the rock wall. We have reached Gorhams Cave, a great teardrop-shaped cavern that disappears into the white cliff face and, upon entering, seems to grow in height and space. This vast, cathedral-like structure, with a roof that soars high into the interior, was used by Neanderthals for tens of thousands of years. Scientists believe it was their last refuge. When Neanderthals disappeared from here, some 32,000 years ago, we became the sole inheritors of our continent.

I pause, perched on a rock inside the entrance, in order to consider this people not so different from myself once sat here, facing the Mediterranean and Africa beyond. Before I arrived in Gibraltar, I used a commercial genome-testing service to analyse my ancestry. From the vial of saliva I sent them, they determined that 1 per cent of my DNA is Neanderthal. I dont know what health advantages or risks these genes have given me testing companies are no longer allowed to provide this level of detail but it is an extraordinary experience to be so close to the intelligent, resourceful people who bequeathed me some of their genes. Sitting in this ancient home, knowing none of them survived to today, is a poignant reminder of how vulnerable we are it could so easily have been a Neanderthal woman sitting here wondering about her extinct human cousins.

Gorhams Cave seems an oddly inaccessible place for a home. But Clive, who has been meticulously exploring the cave for 25 years, explains that the view was very different back then. With the sea levels so much lower, vast hunting plains stretched far out to sea, letting people higher on the rock spot prey and signal to each other. In front of me would have been fields of grassy dunes and lakes wetlands that were home to birds, grazing deer and other animals. Further around the peninsula to my right, where the dunes gave way to shoreline, would have been clam colonies and mounds of flint. It was idyllic, Clive says. The line of neighbouring caves here probably had the highest concentration of Neanderthals living anywhere on Earth. It was like Neanderthal City, he adds.

Deep inside the cave, Clives team of archaeologists have found the remains of fires. Further back are chambers where the inhabitants could have slept protected from hyenas, lions, leopards and other predators. They ate shellfish, pine seeds, plants and olives. They hunted big game and also birds. There was plenty of fresh water from the springs that still exist under what is now seabed, Clive says. They had spare time to sit and think they werent just surviving.

Solid writing: Neanderthal engravings might be the first examples of text ( Tom Sewell)

He and Geraldine have uncovered remarkable evidence of Neanderthal culture in the cave, including the first example of Neanderthal artwork. The hashtag, a deliberately carved rock engraving, is possibly evidence of the first steps towards writing. Other signs of symbolic or ritualistic behaviour, such as the indication that Neanderthals were making and wearing black feather capes or headdresses as well as warm clothes, all point to a social life not so different to the one our African ancestors were experiencing.

Clive shows me a variety of worked stones, bone and antler. I pick up a flint blade and hold it in my hand, marvelling at how the same technology is being passed between people biologically and culturally linked but separated by tens of thousands of years. Other sites in Europe have uncovered Neanderthal-made necklaces of strung eagle talons dating back 130,000 years, little ochre clamshell compacts presumably for adornment, and burial sites for their dead.

These people evolved outside of Africa but clearly had advanced culture and the capability to survive in a hostile environment. Consider modern humans were in the Middle East perhaps 70,000 years ago, and reached Australia more than 50,000 years ago, says Clive. Why did it take them so much longer to reach Europe? I think it was because Neanderthals were doing very well and keeping modern humans out.

But by 39,000 years ago, Neanderthals were struggling. Genetically they had low diversity because of inbreeding and they were reduced to very low numbers, partly because an extreme and rapid change of climate was pushing them out of many of their former habitats. A lot of the forested areas they depended on were disappearing and, while they were intelligent enough to adapt their tools and technology, their bodies were unable to adapt to the hunting techniques required for the new climate and landscapes.

In parts of Europe, the landscape changed in a generation from thick forest to a plain without a single tree, Clive says. Our ancestors, who were used to hunting in bigger groups on the plains, could adapt easily: instead of wildebeest they had reindeer, but effectively the way of capturing them was the same. But Neanderthals were forest people.

It couldve gone the other way if instead the climate had got wetter and warmer, we might be Neanderthals today discussing the demise of modern humans.

Although the Neanderthals, like the Denisovans and other races we are yet to identify, died out, their genetic legacy lives on in people of European and Asian descent. Between 1 and 4 per cent of our DNA is of Neanderthal origins, but we dont all carry the same genes, so across the population around 20 per cent of the Neanderthal genome is still being passed on. Thats an extraordinary amount, leading researchers to suspect that Neanderthal genes must be advantageous for survival in Europe.

Interbreeding across different races of human would have helped accelerate the accumulation of useful genes for the environment, a process that would have taken much longer to occur through evolution by natural selection. Neanderthal tweaks to our immune system, for example, may have boosted our survival in new lands, just as we prime our immune system with travel vaccines today. Many of the genes are associated with keratin, the protein in skin and hair, including some that are linked to corns and others that play a role in pigmentation Neanderthals were redheads, apparently. Perhaps these visible variants were considered appealing by our ancestors and sexually selected for, or perhaps a tougher skin offered some advantage in the colder, darker European environment.

Some Neanderthal genes, however, appear to be a disadvantage, for instance making us more prone to diseases like Crohns, urinary tract disorders and type 2 diabetes, and to depression. Others change the way we metabolise fats, risking obesity, or even make us more likely to become addicted to smoking. None of these genes are a direct cause of these complicated conditions, but they are contributory risk factors, so how did they survive selection for a thousand generations?

Its likely that for much of the time since our sexual encounters with Neanderthals, these genes were useful. When we lived as hunter-gatherers, for example, or early farmers, we would have faced times of near starvation interspersed with periods of gorging. Genes that now pose a risk of diabetes may have helped us to cope with starvation, but our new lifestyles of continual gorging on plentiful, high-calorie food now reveal harmful side effects. Perhaps it is because of such latent disadvantages that Neanderthal DNA is very slowly now being deselected from the human genome.

While I can (sort of) blame my Neanderthal ancestry for everything from mood disorders to being greedy, another archaic human race passed on genes that help modern Melanesians, such as people in Papua New Guinea, survive different conditions. Around the time that the ancestors of modern Europeans and Asians were getting friendly with Neanderthals, the ancestors of Melanesians were having sex with Denisovans, about whom we know very little. Their surviving genes, however, may help modern-day Melanesians to live at altitude by changing the way their bodies react to low levels of oxygen. Some geneticists suspect that other, yet-to-be-discovered archaic races may have influenced the genes of other human populations across the world.

Interbreeding with Neanderthal and other archaic humans certainly changed our genes, but the story doesnt end there.

I am a Londoner, but Im a little darker than many Englishwomen because my father is originally from Eastern Europe. We are attuned to such slight differences in skin colour, face shape, hair and a host of other less obvious features encountered across different parts of the world. However, there has been no interbreeding with other human races for at least 32,000 years. Even though I look very different from a Han Chinese or Bantu person, we are actually remarkably similar genetically. There is far less genetic difference between any two humans than there is between two chimpanzees, for example.

The reason for our similarity is the population bottlenecks we faced as a species, during which our numbers dropped as low as a few hundred families and we came close to extinction. As a result, we are too homogeneous to have separated into different races. Nevertheless, variety has emerged through populations being separated geographically and culturally, in some cases over thousands of years. The greatest distinctions occur in isolated populations where small genetic and cultural changes become exaggerated, and there have been many of them over the 50,000 years since my ancestors made the journey out of Africa towards Europe.

According to the analysis of my genome, my haplogroup is H4a. Haplogroups describe the mutations on our mitochondrial DNA, passed down through the maternal line, and can theoretically be used to trace a migratory path all the way back to Africa. H4a is a group shared by people in Europe, unsurprisingly, and western Asia. It is, the genome-testing company assures me, the same as Warren Buffets. So what journey did my ancestors take that would result in these mutations and give me typically European features?

I was dumped by helicopter in the wilderness with two other people, a Russian and an indigenous Yukaghir man, with our dogs, our guns, our traps, a little food and a little tea. There we had to survive and get food and furs in the coldest place on Earth where humans live naturally minus 60 degrees.

Eske Willerslev lived for six months as a trapper in Siberia in his 20s. Separately, his identical twin brother Rane did the same. When they were teenagers, their father had regularly left them in Lapland to survive alone in the wilderness for a couple of weeks, fostering a passion for the remote tundra and the people who live there, and they went on increasingly lengthy expeditions. But surviving practically alone was very different. It was a childhood dream, but it was the toughest thing I have ever done, Eske admits.

These experiences affected the twins deeply, and both have been driven towards a deeper understanding of how the challenge of survival has forged us as humans over the past 50,000 years. It led Eske into the science of genetics, and to pioneering the new field of ancient DNA sequencing. Now director of the Centre for GeoGenetics at the Natural History Museum of Denmark, Eske has sequenced the worlds oldest genome (a 700,000-year-old horse) and was the first to sequence the genome of an ancient human, a 4,000-year-old Saqqaq man from Greenland. Since then, he has gone on to sequence yet more ancient humans and, in doing so, has fundamentally changed our understanding of early human migration through Europe and beyond. If anyone can unpick my origins, it is surely Eske.

First, though, I go to meet his twin Rane, who studied humanities, went into cultural anthropology and is now a professor at Aarhus University. Hes not convinced that his brothers genetic approach can reveal all the answers to my questions: There exists an uneasy relationship between biology and culture, he tells me. Natural scientists claim they can reveal what sort of people moved around, and they are not interested in having their models challenged. But this cannot tell you anything about what people thought or what their culture was.

To put this point to Eske, I visit him in his delightful museum office, opposite a petite moated castle and in the grounds of the botanic gardens there could scarcely be a more idyllic place for a scientist to work. Greeting him for the first time, just hours after meeting Rane, is disconcerting. Identical twins are genetically and physically almost exactly the same looking back, many years from now, at DNA left by the brothers, it would be all but impossible to tell them apart or even to realise that there were two of them.

Eske tells me that he is increasingly working with archaeologists to gain additional cultural perspective, but that genetic analysis can answer questions that nothing else can. You find cultural objects in certain places and the fundamental question is: Does that mean people who made it were actually there or that it was traded? And, if you find very similar cultural objects, does that mean there was parallel or convergent cultural evolution in the two places, or does that mean there was contact? he explains.

For example, one theory says the very first people crossing into the Americas were not Native Americans but Europeans crossing the Atlantic, because the stone tools thousands of years ago in America are similar to stone tools in Europe at the same time. Only when we did the genetic testing could we see it was convergent evolution, because the guys carrying and using those tools have nothing to do with Europeans. They were Native Americans. So the genetics, in terms of migrations, is by far the most powerful tool we have available now to determine: was it people moving around or was it culture moving around? And this is really fundamental.

What Eske went on to discover about Native American origins rewrote our understanding completely. It had been thought that they were simply descendants of East Asians who had crossed the Bering Strait. In 2013, however, Eske sequenced the genome of a 24,000-year-old boy discovered in central Siberia, and found a missing link between ancient Europeans and East Asians, the descendants of whom would go on to populate America. Native Americans can thus trace their roots back to Europe as well as East Asia.

And what about my ancestors? I show Eske the H4a haplotype analysed by the sequencing company and tell him it means Im European. He laughs derisively. You could be and you could be from somewhere else, he says. The problem with the gene-sequencing tests is that you cant look at a population and work back to see when mutation arose with much accuracy the error bars are huge and it involves lots of assumptions about mutation rates.

This is why ancient genetics and ancient genomics are so powerful you can look at an individual and say, Now we know we are 5,000 years ago, how did it look? Did they have this gene or not?

The things that we thought we understood about Europeans are coming unstuck as we examine the genes of more ancient people. For example, it was generally accepted that pale skin evolved so we could get more vitamin D after moving north to where there was little sun and people had to cover up against the cold. But it turns out that it was the Yamnaya people from much further south, tall and brown-eyed, who brought pale skins to Europe. Northern Europeans before then were dark-skinned and got plenty of vitamin D from eating fish.

It is the same with lactose tolerance. Around 90 per cent of Europeans have a genetic mutation that allows them to digest milk into adulthood, and scientists had assumed that this gene evolved in farmers in northern Europe, giving them an additional food supply to help survive the long winters. But Eskes research using the genomes of hundreds of Bronze Age people, who lived after the advent of farming, has cast doubt on this theory too: We found that the genetic trait was almost non-existent in the European population. This trait only became abundant in the northern European population within the last 2,000 years, he says.

It turns out that lactose tolerance genes were also introduced by the Yamnaya. They had a slightly higher tolerance to milk than the European farmers and must have introduced it to the European gene pool. Maybe there was a disaster around 2,000 years ago that caused a population bottleneck and allowed the gene to take off. The Viking sagas talk about the sun becoming black a major volcanic eruption that could have caused a massive drop in population size, which could have been where some of that stock takes off with lactose.

While ancient genomics can help satisfy curiosity about our origins, its real value may be in trying to unpick some of the different health risks in different populations. Even when lifestyle and social factors are taken into account, some groups are at significantly higher risk of diseases such as diabetes or HIV, while other groups seem more resistant. Understanding why could help us prevent and treat these diseases more effectively.

It had been thought that resistance to infections like measles, influenza and so on arrived once we changed our culture and started farming, living in close proximity with other people and with animals. Farming started earlier in Europe, which was thought to be why we have disease resistance but Native Americans dont, and also why the genetic risks of diabetes and obesity are higher in native Australian and Chinese people than in Europeans.

We sequenced a hunter-gatherer from Spain, and he showed clear genetic resistance to a number of pathogens that he shouldnt have been exposed to, says Eske. Clearly, Europeans and other groups have a resistance that other groups dont have, but is this really a result of the early agricultural revolution in Europe, or is something else going on?

Eskes analysis of people living 5,000 years ago has also revealed massive epidemics of plague in Europe and Central Asia, 3,000 years earlier than previously thought. Around 10 per cent of all skeletons the team analysed had evidence of plague. Scandinavians and some northern Europeans have higher resistance to HIV than anywhere else in the world, Eske notes. Our theory is that their HIV resistance is partly resistance towards plague.

It could be that the cultural changes we have made, such as farming and herding, have had less influence on our genes than we thought. Perhaps it is simply the randomness of genetic mutation that has instead changed our culture. Theres no doubt that where mutations have occurred and spread through our population, they have influenced the way we look, our health risks and what we can eat. My ancestors clearly didnt stop evolving once theyd left Africa were still evolving now and they have left an intriguing trail in our genes.

At the Gibraltar Museum, a pair of Dutch archaeology artists have created life-size replicas of a Neanderthal woman and her grandson, based on finds from nearby. They are naked but for a woven amulet and decorative feathers in their wild hair. The boy, aged about four, is embracing his grandmother, who stands confidently and at ease, smiling at the viewer. Its an unnerving, extraordinarily powerful connection with someone whose genes I may well share, and I recall Clives words from when I asked him if modern humans had simply replaced Neanderthals because of our superior culture.

That replacement theory is a kind of racism. Its a very colonialist mentality, he said. Youre talking almost as if they were another species.

This articlewas first published by Wellcomeon Mosaic and is republished here under a Creative Commons licence

Professor Eske Willerslev is a research associate at the Wellcome Trust Sanger Institute, which is funded by a core grant from the Wellcome Trust, which publishes Mosaic

Here is the original post:
What does it mean to be human? - The Independent

Science Daily

Why do shorter men go bald more often? -- ScienceDaily Science Daily Short men may have an increased risk of becoming bald prematurely. An international genetic study at least points in this direction. During the study, the ... and more »

See original here:
Why do shorter men go bald more often? -- ScienceDaily - Science Daily

He loves dancing to songs, such as Michael Jacksons Beat It and the Macarena, but he cant listen to music in the usual way. He laughs whenever someone takes his picture with a camera flash, which is the only intensity of light he can perceive. He loves trying to balance himself, but his legs dont allow him to walk without support.

He is one in a million, literally.

Born deaf-blind and with a condition, osteopetrosis, that makes bones both dense and fragile, 6-year-old Orion Theodore Withrow is among an unknown number of children with a newly identified genetic disorder that researchers are just beginning to decipher. It goes by an acronym, COMMAD, that gives little away until each letter is explained, revealing an array of problems that also affect eye formation and pigmentation in eyes, skin and hair. The rare disorder severely impairs the persons ability to communicate.

Children such as Orion, who are born to genetically deaf parents, are at a higher risk, according to a recent study published in the American Journal of Human Genetics. The finding has important implications for the deaf community, said its senior author, Brian Brooks, clinical director and chief of the Pediatric, Developmental and Genetic Ophthalmology Section at the National Eye Institute.

It is relatively common for folks in deaf community to marry each other, he said, and whats key is whether each of the couple has a specific genetic misspelling that causes a syndrome called Waardenburg 2A. If yes, theres the likelihood of a child inheriting the mutation from both parents. The result, researchers found, is COMMAD.

Because the disorder was only recently identified, there is much to learn about its impact over a lifetime. Brooks, who estimates that fewer than one person in a million is affected, has seen only a couple cases. Orion is one of them.

When Withrow was pregnant with Orion, she and her husband, Thomas Withrow Jr., suspected that he might be born deaf. While their daughter, 11-year-old Anastasia, has normal hearing, their other son, 12-year-old Skyler, is deaf. Then the results of initial imaging showed their third child would likely be born blind.

A subsequent MRI raised even more worries, suggesting that they were confronting trisomy 13, a chromosomal condition involving devastating physical abnormalities. Her doctor recommended the pregnancy be terminated.

We just closed that discussion quick, Withrow recalled through an interpreter. It is sad when people think, Oh well, he is going to be disabled so go ahead and end his life. Its in Gods hands. It was not my decision to make, and it wasnt my husbands decision to make.

Even though he could not see, Orions right eye would occasionally react to bright light. At just several months of age, he had special prostheses similar to jumbo contact lensescalled shellsinserted over his eyeballs to allow the sockets to grow proportionally with his face. And he started physical therapy to improve his motor functions. By the time he was 18 months old, he was able to keep his head straight, his mother said.

COMMAD explains those problems and others, Withrow now knows. It stands for coloboma (a condition in which normal tissue in or around the eye is missing), osteopetrosis (abnormally dense bones prone to fracture), microphthalmia (small or abnormally formed eyes), macrocephaly (abnormal enlargement of the head), albinism (lack of pigment or more specifically melanin in the skin, hair, and eyes) and deafness.

COMMAD can affect Orion in unusual ways. His body clock keeps its own schedule, his mother said, making it difficult for him to distinguish day and night: He would think its morning outside at 2 a.m., and he would want to play at a time when we want to go to sleep.

Excerpt from:
A mysterious medical condition gets a name - and a genetic link to deafness - Napa Valley Register

Cambridge University researchers mixed two kinds of mouse stem cell and placed them on a 3D scaffold. After four days of growth in a tank of chemicals designed to mimic conditions in the womb, the cells formed the structure of a living mouse embryo.

The breakthrough has been described as a "masterpiece" in bioengineering that might eventually allow scientists to grow human embryos without sperm or an egg.

Growing embryos would help researchers study the early stages of human life so they could understand why some pregnancies fail but the research is likely to raise questions about what constitutes human life.

Currently scientists can carry out experiments on embryos left over from IVF treatments but they are in short supply and must be destroyed after 14 days.

Scientists say that being able to create unlimited numbers of embryos in the lab could speed up research and perhaps overcome some of the ethical boundaries.

"We think that it will be possible to mimic a lot of the embryological development events occurring before 14 days using human stem cells," said the university's Magdalena Zernicka-Goetz, who led the research.

"We are very optimistic that this will allow us to study key events of this critical stage of human development without having to work on [IVF] embryos. Knowing how development normally occurs will allow us to understand why it so often goes wrong."

The embryos were created using genetically engineered stem cells coupled with extra-embryonic trophoblast stem cells, which form the placenta in a normal pregnancy.

Previous attempts to grow embryos using only one kind of stem cell proved unsuccessful because the cells would not assemble into their correct positions. But scientists discovered that when they added the second "placental" stem cells the two types of cell began to "talk to each other", telling each other where to assemble.

Together they eventually melded to form an embryonic structure, with two distinct clusters of cells at each end and a cavity in the middle in which the embryo would continue to develop. The embryo would not grow into a mouse because it lacked the stem cells that would make a yolk sack.

However, such work raises ethical questions about the "sanctity" of human life and whether it should be manipulated or created in the lab. Critics warn that allowing embryos to be grown for science opens the door to designer babies and genetically modified humans.

David King, director of the watchdog group Human Genetics Alert, said: "What concerns me about the possibility of artificial embryos is that this might become a route to creating genetically modified or even cloned babies.

"Until there is an enforceable global ban on those possibilities, as we saw with mitochondrial transfer, this kind of research risks doing the groundwork for entrepreneurs, who will use the technologies in countries with no regulation."

UK scientists will need to get permission from the Human Fertility and Embryology Authority before attempting to create human embryos using the technique, and experts have called for international dialogue before research can be allowed to progress.

Originally posted here:
Lab-grown humans soon - Times LIVE

A sweeping international effort is connecting the dots between genes in our fat cells and our risk for obesity and cardiometabolic diseases such as heart disease and type 2 diabetes. The researchers have identified approximately 90 genes found in fat that could play important roles in such diseases and could be targeted to develop new treatments or cures.

Unlike many genetics studies, the huge project looked at how genes activity actually manifests in human patients in this case, 770 Finnish men. The results will help doctors and scientists better understand how normal gene variations can affect individuals health and risk for disease.

There are a lot of regions in our genomes that are associated with increased risk for, lets say, type 2 diabetes. But we dont always understand whats happening in these regions, said Mete Civelek of the University of Virginia School of Medicine. This study actually addresses some of those questions.

The men used in the study have had their health histories, body composition, blood work and other wellness factors recorded in astoundingly complete detail Civelek called them one of the very few extremely well-characterized populations in the world.

The precise documentation allowed the researchers to draw conclusions about the effects of gene variations that naturally occur in subcutaneous fat. Type 2 diabetes, coronary artery disease and obesity are multifactorial and complex diseases, Civelek said. Genetic factors do not work in isolation they work in a holistic way, so I think that these kind of studies that we are publishing are key to understanding whats happening in human populations.

That understanding could translate into better treatments for cardiometabolic diseases that pose a tremendous public health threat. Heart disease, for example, is the No. 1 killer in the United States. Maybe by looking at these other markers we will be able to predict someones risk much better, so that, for example, they can modify their diet or lifestyle even before type 2 diabetes develops, Civelek said. Or lets say type 2 diabetes has already developed. We might be able to target some of these novel genes as a potential cure.

The project helps advance a more sophisticated and three-dimensional view of our DNA. Typically, people think of DNA as long, neat strands, laid out like a stretched string. But in reality, the strands are clumped together inside cells like spaghetti. Genes that appear far away from each other when viewed linearly actually may be quite close when DNA is balled up inside the cell. That physical proximity affects what they do.

For a lot of cases, what we found was that these different genomic regions actually affect gene expression in a far-away locus, not necessarily the immediate neighborhood, he said. Thats because the DNA is compacted and theres a three-dimensional structure. [Genes] can actually come together in three-dimensional space and can affect each other.

That can have big implications for understanding what genes are doing. Were saying that it may be the gene that we thought was causing a phenomenon is not, Civelek said. There may actually be another gene at work that is a little bit farther away.

Civelek, of UVAs Department of Biomedical Engineering, is already hard at work on a follow-up to the project, examining a potential master switch that may be regulating the activity of many different genes associated with obesity, HDL (or good) cholesterol level and risk for type 2 diabetes.

The project included researchers from UVA; the University of North Carolina at Chapel Hill; the University of California, Los Angeles; Bristol-Myers Squibb; the University of Eastern Finland; the University of Michigan, Ann Arbor; the National Institutes of Healths National Human Genome Research Institute; and Kings College London. Their findings have been published in the American Journal of Human Genetics.

The work received financial support from the National Institutes of Health, the Academy of Finland, the Finnish Heart Foundation, the Finnish Diabetes Foundation, the Finnish Funding Agency for Technology and Innovation, and the Commission of the European Community. Bristol-Myers Squibb also contributed.

Read the original here:
90 Genes in Fat Cells May Contribute to Dangerous Diseases - UVA Today (press release) (registration)

Mirror photo by Cherie Hicks Michael Farrow sits in his Altoona home next to an 1850 marble fireplace that came from his aunts house in Philadelphia. The author of Altoonas Historic Mishler Theatre will receive the 2016 Angel of the Arts award from the Blair County Foundation on Saturday.

Michael Farrow was educated in human genetics and spent a career in the emerging field. But he has spent his retirement indulging his love of history and the arts, roused by youthful summers spent at his grandparents in Philadelphia.

He researched and wrote Altoonas Historic Mishler Theatre, published last year. For that, the Blair County Arts Foundation is honoring him with its 2016 Angel of the Arts award at its annual dinner on Saturday.

He devoted three years of his life to it and is giving all the proceeds to the Mishler, said Kate Shaffer, BCAF executive director.

She said the 174-page hardback book created a magnificent retrospective of the Mishlers past, present and potential.

Farrow said the award surprises him because even though he was born and mostly raised in Altoona, he went away for his college and career.

Im just somebody who came back to town (six) years ago after being gone for years, he said.

Farrow wasnt supposed to grow up here. Less than a year after he was born, his father, a medical doctor, took the family and his practice to a Boston suburb to take care of soldiers returning from World War II.

But, in 1943, when Farrow was 4, his father contracted strep throat from a patient and died; penicillin, only recently discovered, was not widely available.

The family eventually returned to Altoona, where Farrow attended Adams Elementary, Roosevelt Junior High and Altoona High, graduating in 1957. Summers were spent crisscrossing Philadelphia for its historical sites, museums and art.

For 12 years, I was immersed in all this history, said Farrow.

Although his grandparents were of Lebanese descent having immigrated in the late 19th century they lived near a neighborhood of working-class Italian immigrants, who would sit on their front stoops, talk and listen to music blaring from inside. That is where Farrow picked up his love of opera.

He bragged on the Altoona schools music programs, and he was in the band. He also spent a lot of time in movie theaters there were 10 in Altoona in the 1950s, he noted.

Farrow didnt consider music or art as a career because he was afraid he would end up as a teacher, an occupation he didnt want.

Just as he was getting his bachelors in biology from Juniata College in 1961, details of DNA were emerging, even though research had been devoted to agriculture.

Farrow then went to West Virginia University, earning his masters and doctorate in human genetics in 1970. He spent a one-year fellowship as a genetic counselor at WVU, fielding questions from mothers in the regions hollows and researching drugs used in leukemia patients.

Genetics was an up and coming field and the more I got into it, I found it fascinating, he said.

Drug companies began studying how their drugs and chemicals affected human genetics. Farrow went to work for Wyeth in Philadelphia, creating its first genetics lab and conducting tests to determine the toxicologic effect of chemicals and drugs on bacteria, animals and humans.

Then the federal Environmental Protection Agency began researching the effects of pesticides on humans and contracted with research companies to set up testing procedures. Farrow left Wyeth for Washington, D.C., and got in on the ground floor of breakthrough government research.

He worked for several contractors, building genetics laboratories, developing testing protocols and researching the effects of pesticides and drugs on humans. He spent the last two dozen years of his career working to get drugs and chemicals registered for government controls.

Farrow retired in 2005 and decided five years later to return to Altoona to be near his siblings after his mother died.

He delved into history research, publishing his first book on all those movie theaters he had visited as a youngster. Now Showing: A History of Altoona and Blair County Theatres was published in 2013 and sold out in two months.

Then he took a month off before starting Altoonas Historic Mishler Theatre.

Farrow now works on myriad projects for the Blair County Historical Society and its Baker Mansion, as a board member, and researching historical venues and conducting lectures and tours, such as historical neighborhoods and churches.

The fourth-generation Lebanese-American also plans to write a history on the 100 or so families that immigrated from Lebanon and Syria to Altoona well over a century ago.

If you really love something that doesnt have a lot of opportunities, make it your hobby and make a living at something you love as well, he said.

That hobby, he said, also helps him support causes that he loves.

I like Altoona and all the arts. They need money, he said. How can I support them if Im not a millionaire? I can lend my talent. Plus I get a high finding the history and these little unknown tidbits that are fascinating.

Mirror Staff Writer Cherie Hicks is at 949-7030.

SOMERSET, Pa. (AP) Former Penn State assistant football coach Jerry Sandusky has been moved from a ...

Jacey Whitcomb Age: 15 School: Tyrone Area School District Family: Parents, Kim and Jason Whitcomb FFA ...

CARROLLTOWN National, state and local Farm Bureau members will converge on Carrolltown March 29 as the Cambria ...

Tyrone students attend ACES conference Thirteen Tyrone Area FFA members recently traveled to Harrisburg to ...

Little more than a month after an infectious virus was first identified on the Penn State University Park campus, ...

Follow this link:
History is Altoona man's hobby, and genetics is livelihood - Altoona Mirror

Ian Green | The Daily Wildcat

Dr. Thomas Doetschman, Ph.D., examines the embryonic cells used to study and implant mutated and disease genes; if the mutated gene successfully imbeds itself into a sperm or egg cell, the resulting rat that is born will be studied to research the effects of that same disease genes in humans. CRISPR CAS9 is technology that allows the splicing of genes to both remove and replace particular DNA strands. CRISPR can affect either just the patient or his descendants as well, depending on the technique used.

Published Mar 5, 2017 6:00am

A new genome editing technology known as CRISPR has the potential to revolutionize the way scientists study diseases and genetics.

I think its a really useful tool for science, in fact its sort of revolutionizing the speed at which we can accomplish certain things in the laboratory and it has tremendous potential for therapeutic applications, said Kimberly McDermott, a research associate professor of medicine and an associate professor of cellular and molecular medicine, cancer biology and genetics.

Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR-Cas9, is based off a bacterial immune system, said Thomas Doetschman, professor of cancer biology, genetics and cellular and molecular medicine.

When bacteria become infected by a virus, they take pieces of the viruss DNA and incorporate it into their own genome. This allows the bacteria to recognize and attack the virus if it ever appears again. This system allows them to destroy the virus, but it also allows them to destroy DNA, Doetschman said.

In developing CRISPR, scientists took a hint from the bacteria.

What it [CRISPR] actually does is causes a mutation at that site, in the DNA, and then repairs it, Doetschman said. And you can repair it in different ways, such that you can actually modify the sequence of the DNA.

This has enormous implications for the study of genetics and combating human diseases. And while it may sound exciting, human gene editing isnt all fun and games.

There are two ways the CRISPR technology can be used in humans, Doetschman said. The first way is to alter somatic cells, which dont get passed down to the next generation. This would only affect the patient who is receiving the treatment.

The second way, known as the germline, can have serious long-lasting effects. Altering genes in the germline can produce permanent changes in the patient that will then be passed on to their children.

Theres two completely different ways of doing this, and the real concern, the big concern, is that it be used by some unscrupulous people to try to change the germline of people, so that you can create progeny that will all have this kind of modification, Doetschman said.

And CRISPR isnt just for humans; it can be used to edit plant cells as well.

It could alter genes in a plant so that the plant either becomes resistant to or susceptible to agents that might otherwise kill the plant, Doetschman said. This could mean disease-resistant plants or increased nutritional content.

One of CRISPRs greatest contributions is in the realm of research, specifically for understanding normal development and disease processes, McDermott said.

For example, in the future scientists may be able to grow human organs from the patients own cells, using CRISPR.

RELATED:Beefy bugs: antibiotic-resistant bacteria pose threat to health

Recent studies on mice and rats have introduced the possibility of using a model organism, such as a pig, to grow human organs, McDermott said.

Another exciting possibility available through CRISPR involves induced pluripotent stem cells, Doetschman said. This process essentially works as a time machine for your cells.

Doetschman describes it as the ability to put your own cells, such as skin cells, in culture and de-differentiate those cells back down to the pluripotent "master key" stem cell, using CRISPR. Once your adult cells are transformed into stem cells, you can make the genetic modifications you'd like, such as correcting a mutation and then re-differentiate the stem cells back into the cell type of the tissue you want to correct.

These cells could potentially be engrafted back into the patients disease tissue, Doetschman said.

Dr. Thomas Doetschman, Ph.D., describes a few of the many functions performed in the workspace pictured, which can effectively seal itself to create a sterile and airtight environment in which researchers can operate. CRISPR technology may redefine the future of genetics.

When it comes to working with human therapeutics, safety and regulations are extremely important, McDermott said. As scientists, their primary concern is to minimize and prevent harm in every way possible.

One of these regulations is a patent that was recently issued to the MIT and Harvard-affiliated Broad Institute, one of the centers responsible for creating CRISPR technology.

RELATED:UA researchers win NIH grant for autoimmune disease work

Despite heavy public controversy surrounding the patent, Doetschman said the patent is a good thing, because it will allow scientists to ensure that CRISPR research is carried out in a safe way, especially in regards to human use.

I think from a scientists perspective, the thing that were really focusing on is trying to listen to our colleagues but also the public in general about what are the fears of this technology, McDermott said. Of course when you start to edit genes and mutate genes theres a lot of concerns about what might happen.

As for the future of human genetics research, both Doetschman and McDermott remain optimistic.

While scientists may have had the ability to make mutations in cells in the past, the results were usually inefficient and could produce off-target effects, McDermott said. CRISPR improves both the efficiency and the accuracy of genome research.

CRISPR might not be the cure to every disease, but it is the key to unlock many avenues of research, Doetschman said.

In terms of the research end of science and medical research, its expanding tremendously the scientists ability to ask questions about genetic disease, Doetschman said.

Doetschman currently uses the CRISPR technology to study mice in his lab on campus. You can readabout his research here.

Follow Hannah Dahl onTwitter.

Read the original here:
CRISPR gene editing tech brings countless opportunities and challenges - Arizona Daily Wildcat

Special To The Washington Post.

He loves dancing to songs, such as Michael Jackson's "Beat It" and the "Macarena," but he can't listen to music in the usual way. He laughs whenever someone takes his picture with a camera flash, which is the only intensity of light he can perceive. He loves trying to balance himself, but his legs don't allow him to walk without support.

He is one in a million, literally.

Born deaf-blind and with a condition, osteopetrosis, that makes bones both dense and fragile, 6-year-old Orion Theodore Withrow is among an unknown number of children with a newly identified genetic disorder that researchers are just beginning to decipher. It goes by an acronym, COMMAD, that gives little away until each letter is explained, revealing an array of problems that also affect eye formation and pigmentation in eyes, skin and hair. The rare disorder severely impairs the person's ability to communicate.

Children such as Orion, who are born to genetically deaf parents, are at a higher risk, according to a recent study published in the American Journal of Human Genetics. The finding has important implications for the deaf community, said its senior author, Brian Brooks, clinical director and chief of the Pediatric, Developmental and Genetic Ophthalmology Section at the National Eye Institute.

"It is relatively common for folks in deaf community to marry each other," he said, and what's key is whether each of the couple has a specific genetic "misspelling" that causes a syndrome called Waardenburg 2A. If yes, there's the likelihood of a child inheriting the mutation from both parents. The result, researchers found, is COMMAD.

Because the disorder was only recently identified, there is much to learn about its impact over a lifetime. Brooks, who estimates that fewer than one person in a million is affected, has seen only a couple cases. Orion is one of them.

The study's finding made things clearer for Heather Withrow, Orion's mother. "It was more like an 'Oh, cool, that explains it!' kind of discovery," she said from Austin, Texas, where the family lives.

When Withrow was pregnant with Orion, she and her husband, Thomas Withrow Jr., suspected that he might be born deaf. While their daughter, 11-year-old Anastasia, has normal hearing, their other son, 12-year-old Skyler, is deaf. Then the results of initial imaging showed their third child would likely be born blind.

A subsequent MRI raised even more worries, suggesting that they were confronting trisomy 13, a chromosomal condition involving devastating physical abnormalities. Her doctor recommended the pregnancy be terminated.

"We just closed that discussion quick," Withrow recalled through an interpreter. "It is sad when people think, 'Oh well, he is going to be disabled so go ahead and end his life.' It's in God's hands. It was not my decision to make, and it wasn't my husband's decision to make."

The couple started to educate themselves about deaf-blindness - a combination that magnifies the effects of each condition. They contacted resources such as Connections Beyond Sight and Sound, a Maryland-based project that helps parents of deaf-blind children. A meeting with one of its specialists was empowering preparation. "It helped us. It let us know that we could celebrate and be happy when he was born, and not be surprised," Withrow said.

Which is what happened. "We fell in love with him at first sight," she said. As she has described on a blog she writes, Orion was long and lean, "with snowy white hair and lashes, ice-melting smile, rich laughter."

Even though he could not see, Orion's right eye would occasionally react to bright light. At just several months of age, he had special prostheses similar to "jumbo" contact lenses - called shells - inserted over his eyeballs to allow the sockets to grow proportionally with his face. And he started physical therapy to improve his motor functions. By the time he was 18 months old, he was able to keep his head straight, his mother said.

COMMAD explains those problems and others, Withrow now knows. It stands for coloboma (a condition in which normal tissue in or around the eye is missing), osteopetrosis (abnormally dense bones prone to fracture), microphthalmia (small or abnormally formed eyes), macrocephaly (abnormal enlargement of the head), albinism (lack of pigment or more specifically melanin in the skin, hair, and eyes) and deafness.

COMMAD can affect Orion in unusual ways. His body clock keeps its own schedule, his mother said, making it difficult for him to distinguish day and night: "He would think it's morning outside at 2 a.m., and he would want to play at a time when we want to go to sleep."

Such differences sometimes wear down his parents. "Despite all that, everything we do with him and everything he learns is so worth it," Withrow said.

She frequently blogs about Orion's experiences - she calls her site "A Mom's Musings" - to help educate people about COMMAD and help other parents interact with deaf-blind children. At home, she and the rest of the family use a touch-based version of American Sign Language - teaching with objects such as a baby bottle, diaper and spoon - to communicate with Orion.

The caveat of the National Eye Institute's recent study is that knowledge about how to care for and interact with children who have COMMAD is still in its infancy, Brooks said. "We are trying to understand the best ways to listen to the children," he said.

For Withow, sharing knowledge is comforting.

"Orion's life is just as important as everyone else's," she said, "and we hope he has the same opportunities as others."

health-commad

_____

Keywords: deaf-blindness, rare genetic disorder, genetic mutation causing deafness, COMMAD, National Eye Institute

Visit link:
A mysterious medical condition gets a name - and a genetic link to deafness - Reading Eagle