GENETICS: Unlocking Humanity's Past and Future

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Re: Genetics: Unlocking Humanity's Past and Future

Genetics: Future

For the first time, living cells have formed carbon-silicon bonds
Life—but not as we know it.

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Scientists have managed to coax living cells into making carbon-silicon bonds, demonstrating for the first time that nature can incorporate silicon - one of the most abundant elements on Earth - into the building blocks of life.

While chemists have achieved carbon-silicon bonds before - they’re found in everything from paints and semiconductors to computer and TV screens - they’ve so far never been found in nature, and these new cells could help us understand more about the possibility of silicon-based life elsewhere in the Universe.

After oxygen, silicon is the second most abundant element in Earth’s crust, and yet it has nothing to do with biological life.

Why silicon has never been incorporated into any kind of biochemistry on Earth has been a long-standing puzzle for scientists, because, in theory, it would have been just as easy for silicon-based lifeforms to have evolved on our planet as the carbon-based ones we know and love.

Not only are carbon and silicon both extremely abundant in Earth’s crust - they’re also very similar in their chemical make-up.

One of the most important features carbon and silicon share is the ability to form bonds with four atoms at the same time. This means they're capable of linking together the long chains of molecules needed to form the basis of life as we know it - proteins and DNA.

And yet, silicon-based lifeforms do not exist outside the Star Trek universe - as far as we know.

"No living organism is known to put silicon-carbon bonds together, even though silicon is so abundant, all around us, in rocks and all over the beach," says one of the researchers, Jennifer Kan from Caltech.

To be clear, Kan and her team played a big role in getting living cells to achieve carbon-silicon bonds - this was not something that the cell could have easily done on its own.

But the experiment is proof that these bonds can be formed in nature - so long as you have the right conditions.

The researchers started by isolating a protein that occurs naturally in the bacterium Rhodothermus marinus, which thrives in the hot springs of Iceland.

They liked this protein, called cytochrome c enzyme, because while its main role is to transport electrons through the cells, lab tests revealed that it could facilitate the kinds of bonds that could attach silicon atoms to carbon.

After isolating the protein, they inserted the gene for it into some E. coli bacteria to if it could facilitate the production of carbon-silicon bonds inside its living cells.

The first iteration of these silicon-engineered bacteria didn’t do much, but the team continued to mutate the protein gene within a specific region of the E. coli genome until something very cool happened.

"After three rounds of mutations, the protein could bond silicon to carbon 15 times more efficiently than any synthetic catalyst," Aviva Rutkin reports for New Scientist.

The fact that this bacterium has been engineered to produce carbon-silicon bonds more efficiently than chemists can in the lab is exciting for two reasons. First, it offers up a better way to produce the carbon-silicon bonds we need to make things like pharmaceuticals, agricultural chemicals, and fuels.

"This is something that people talk about, dream about, wonder about," Annaliese Franz from the University of California, Davis, who wasn’t involved in the research, told New Scientist.

"Any pharmaceutical chemist could read this on Thursday and on Friday decide they want to take this as a building block that they could potentially use."

Secondly, it signifies that a lifeform could potentially be at least partially based on silicon, and if the researchers continue to grow these kinds of bacteria, we could get a better understanding of what they could look like.

"This study shows how quickly nature can adapt to new challenges," one of the team, Frances Arnold, said in a press statement.

"The DNA-encoded catalytic machinery of the cell can rapidly learn to promote new chemical reactions when we provide new reagents and the appropriate incentive in the form of artificial selection. Nature could have done this herself if she cared to."

The research has been published in Science.

 

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Re: Genetics: Unlocking Humanity's Past and Future

Neanderthals' genetic legacy

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Okay, so we know that Neanderthals gave humans, especially the Caucasoids, those white skin and blue eyes. For those who still don't get it, let's get back to a basic fact about the human race: all humans in the world today came from the last population of 10,000 Africans who left Africa because of the extreme weather conditions brought about by the Ice Ages. All the genetic markers conclusively point to this fact. When the weather got better, some of them went back to Africa and retained their pure genetic makeup. Two population groups however, mixed in and interbred with two more ancient (there's a third mysterious group)—scientists prefer the word "archaic," thank you—human species, the Denisovans and the Neanderthals. Who are the modern people who carry the Neanderthal and Denisovan genes? These would be our next topics for this thread. First, let's start with the Neanderthals.

Remnants of Neanderthal DNA in modern humans are associated with genes affecting:

• Type II diabetes
• Crohn's disease
  
• lupus
  
• biliary cirrhosis
  
• smoking behavior.
  

They also concentrate in genes that influence skin and hair characteristics. At the same time, Neanderthal DNA is conspicuously low in regions of the X chromosome and testes-specific genes.

The research, led by Harvard Medical School geneticists and published Jan. 29 in Nature, suggests ways in which genetic material inherited from Neanderthals has proven both adaptive and maladaptive for modern humans. (A related paper by a separate team was published concurrently in Science.)

"Now that we can estimate the probability that a particular genetic variant arose from Neanderthals, we can begin to understand how that inherited DNA affects us," said David Reich, professor of genetics at HMS and senior author of the paper. "We may also learn more about what Neanderthals themselves were like."

In the past few years, studies by groups including Reich's have revealed that present-day people of non-African ancestry trace an average of about 2 percent (note: recent studies indicate 4-5 percent is the likelier figure) of their genomes to Neanderthals—a legacy of interbreeding between humans and Neanderthals that the team previously showed occurred between 40,000 to 80,000 years ago. (Indigenous Africans have little or no Neanderthal DNA because their ancestors did not breed with Neanderthals, who lived in Europe and Asia.)

Several teams have since been able to flag Neanderthal DNA at certain locations in the non-African human genome, but until now, there was no survey of Neanderthal ancestry across the genome and little understanding of the biological significance of that genetic heritage.

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"The story of early human evolution is captivating in itself, yet it also has far-reaching implications for understanding the organization of the modern human genome," said Irene A. Eckstrand of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the research. "Every piece of this story that we uncover tells us more about our ancestors' genetic contributions to modern human health and disease."

Deserts and Oases
Reich and colleagues—including Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Germany—analyzed genetic variants in 846 people of non-African heritage, 176 people from sub-Saharan Africa, and a 50,000-year-old Neanderthal whose high-quality genome sequence the team published in 2013.

The most powerful information the researchers used to determine whether a gene variant came from a Neanderthal was if the variant appeared in some non-Africans and the Neanderthal but not in the sub-Saharan Africans.

Using this and other types of information, the team found that some areas of the modern non-African human genome were rich in Neanderthal DNA, which may have been helpful for human survival, while other areas were more like "deserts" with far less Neanderthal ancestry than average.

The barren areas were the "most exciting" finding, said first author Sriram Sankararaman of HMS and the Broad Institute. "It suggests the introduction of some of these Neanderthal mutations was harmful to the ancestors of non-Africans and that these mutations were later removed by the action of natural selection."

The team showed that the areas with reduced Neanderthal ancestry tend to cluster in two parts of our genomes: genes that are most active in the male germline (the testes) and genes on the X chromosome. This pattern has been linked in many animals to a phenomenon known as hybrid infertility, where the offspring of a male from one subspecies and a female from another have low or no fertility.

"This suggests that when ancient humans met and mixed with Neanderthals, the two species were at the edge of biological incompatibility," said Reich, who is also a senior associate member of the Broad Institute and an investigator at the Howard Hughes Medical Institute. Present-day human populations, which can be separated from one another by as much as 100,000 years (such as West Africans and Europeans), are fully compatible with no evidence of increased male infertility. In contrast, ancient human and Neanderthal populations apparently faced interbreeding challenges after 500,000 years of evolutionary separation.

"It is fascinating that these types of problems could arise over that short a time scale," Reich said.

A Lasting Heritage
The team also measured how Neanderthal DNA present in human genomes today affects keratin production and disease risk.

Neanderthal ancestry is increased in genes affecting keratin filaments. This fibrous protein lends toughness to skin, hair and nails and can be beneficial in colder environments by providing thicker insulation, said Reich. "It's tempting to think that Neanderthals were already adapted to the non-African environment and provided this genetic benefit to humans," he speculated.

The researchers also showed that nine previously identified human genetic variants known to be associated with specific traits likely came from Neanderthals. These variants affect diseases related to immune function and also some behaviors, such as the ability to stop smoking. The team expects that more variants will be found to have Neanderthal origins.

The team has already begun trying to improve their human genome ancestry results by analyzing multiple Neanderthals instead of one. Together with colleagues in Britain, they also have developed a test that can detect most of the approximately 100,000 mutations of Neanderthal origin they discovered in people of European ancestry; they are conducting an analysis in a biobank containing genetic data from half a million Britons.

"I expect that this study will result in a better and more systematic understanding of how Neanderthal ancestry affects variation in human traits today," said Sankararaman.

As another next step, the team is studying genome sequences from people from Papua New Guinea to build a database of genetic variants that can be compared to those of Denisovans, a third population of ancient humans that left most of its genetic traces in Oceania but little in mainland Eurasia.
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Re: Genetics: Unlocking Humanity's Past and Future

Paying a heavy price for loving the Neanderthals

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One of the biggest surprises about our evolution revealed over just the last decade is the extent to which our ancestors engaged in amorous congress with the evolutionary cousins.​

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One of the biggest surprises about our evolution revealed over just the last decade is the extent to which our ancestors engaged in amorous congress with the evolutionary cousins.

Bonking the Neanderthals, it seems, was a bit of a pastime for the distant relatives. It happened many times in Siberia, East Asia, the Middle East and Europe, and across a long period between 100,000 and 40,000 years ago.

In reality, we have no idea of course exactly how many times it occurred, nor the circumstances in which it happened. Who instigated it, us or them? Was it consensual? Did they pair for life? Or was it a casual fling?

Now, the consequences of interbreeding for us today are becoming all too clear from studies of the genome - theirs and ours - ancient and modern.
Somewhere between 1.5% and 2.1% of your genome was inherited from the Neanderthals, assuming your ancestry was non-African of course.

East Asians typically have more Neanderthal DNA because their ancestors partook in a little more afternoon delight than the rest of ours did.

For Indigenous people living around eastern Indonesia, and in New Guinea and Australia, their ancestors also took a shine to the ‘Denisovans’. In their genomes we find n extra 4% to 6%inherited from this mysterious species.

So far, archaeologists have found just two finger bones and a tooth from the Denisovans, thousands of kilometres away from New Guinea in southern Siberia, of all places.

Yet, the fact that the earliest New Guineans mated with the Denisovans only 44,000 years ago - as revealed by their DNA - suggests that all the action happened in the tropical climes of Oceania, not icy Siberia.

Don’t fret if you’re ancestry is African, though: your ancestors found another human species or two to bonk.

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Surprisingly, the genomes of the West African Biaka and Baka (so-called ‘pygmy’) people have revealed DNA from a completely unknown species, which found its way into the human genome only 9,000 years ago.

Other studies have found much wider evidence for interbreeding across Africa, occurring sometime around 35,000 years ago.

It’s fun to think about our surprisingly mixed-up heritage as a species. And may be even poke fun at a friend or two for their seemingly excessive amounts of Neanderthal DNA.

But there’s a serious side to all of this as well. The legacy of interbreeding is very real and seems to explain quite a few modern ailments, and some rather nasty diseases as well.

Neanderthal DNA is associated with an increased risk of developing skin corns and callosities, mood disorders and depression, overweight and obesity, upper respiratory and urinary tract infections, incontinence, hardening of the arteries and even smoking.

Then there’s those immediate risks that come with casual sex with your own, or in this case, another species.

Like catching a parasite such as body lice, or worse still, contracting a sexually transmitted infection.

Body lice are parasites that evolve in tandem with their hosts. Other mammals have them, but human lice species are unique to us, and spread through close contact such a sex.

A person can be infested with thousands of these blood suckers, each insect biting five times a day.

But worse, they also carry deadly bacteria. Diseases like endemic typhus are carried and spread by body lice and are said to have caused more deaths than all the wars in history put together.

Genetic studies of body lice suggest that one of the two species that infects us today evolved more than a million years ago, in association with another human-like species.

What’s the implication here? Yet again, we probably got body lice because our ancestors engaged in the pants-off dance off with an evolutionary cousin.

Now a new study has found that a particular human papillomavirus (HPV16), one of the most common sexually transmitted infections with 14 million new cases each year in the US alone, was also inherited from the Neanderthals.

The amazing diversity of HPV16 variants across Asia and Europe - compared with low diversity in Africa - has long puzzled researchers.

You’d expect the opposite situation because we evolved in Africa and presumably carried HPV16 out with us when we left there 100,000 years ago or more.

This new study solves the mystery by showing that modern humans brought only a small subset of HPV16 variants out of Africa, picking up most of the other strains after they (ah, we) bonked the Neanderthals.

Technically, this is known as a host-shift, where sexual contact with archaic populations led to the transmission of new variants of HPV16 to us.

With time, even more diversity was generated as modern humans spread across the rest of the Old and New Worlds.

High risk human papillomaviruses are a serious global health issue. They’re associated with around 5 percent of all cancers worldwide.

The choice our ancestors made to interbreed with the Neanderthals, Deniosvans and probably numerous other archaic cousins have left us with profound legacies that we’re only beginning to learn about.

What else might they have done that had profound consequences for us today?

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Makes me wonder just how the decisions we make today - the changes we’re wreaking on the planet - will shape the evolution of Homo sapiens in 1,000, or even 10,000, years from now? One thing’s for certain, they will.

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Re: Genetics: Unlocking Humanity's Past and Future

Interrupt regular post for this:

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How we became more than 7 billion – humanity’s population explosion, visualised​

From our origins in Africa, humans began migrating around the globe roughly 100,000 years ago. But it was only with the advent of agriculture about 12,000 years ago that our population started to swell to more than a million. This data visualisation from the American Museum of Natural History beautifully charts humanity’s stunning – and increasingly alarming – exponential expansion to our current population of roughly 7.4 billion.

Video by the American Museum of Natural History
Producer: Laura Moustakerski
Animator: Shay Krasinksi

- - - Updated - - -

Animated map shows how humans migrated across the globe

 

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Re: Genetics: Unlocking Humanity's Past and Future

​genetics: denisovans

Why I Am Denisovan
The Genetic Legacy of Denisovans

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The flood of information tying up genetics to archaic ancestry has apparently led to some dark jokes and humor around internet boards. It is helped by some business ventures selling DNA kits to allow individuals to determine how they are doing in this category.

Last time I have profiled the Neanderthals and their genetic legacy.

This time around I'm going to feature the Denisovan contribution to human genetic pool.

Early human history was a promiscuous affair. As modern humans began to spread out of Africa roughly 50,000 years ago, they encountered other species that looked remarkably like them — the Neanderthals and Denisovans, two groups of archaic humans that shared an ancestor with us roughly 600,000 years earlier. This motley mix of humans coexisted in Europe for at least 2,500 years, and we now know that they interbred, leaving a lasting legacy in our DNA.

Over the last few years, scientists have dug deeper into the Neanderthal and Denisovan sections of our genomes and come to a surprising conclusion. Certain Neanderthal and Denisovan genes seem to have swept through the modern human population — one variant, for example, is present in 70 percent of Europeans — suggesting that these genes brought great advantage to their bearers and spread rapidly.

“In some spots of our genome, we are more Neanderthal than human,” said Joshua Akey, a geneticist at the University of Washington. “It seems pretty clear that at least some of the sequences we inherited from archaic hominins were adaptive, that they helped us survive and reproduce.”

But what, exactly, do these fragments of Neanderthal and Denisovan DNA do? What survival advantage did they confer on our ancestors? Scientists are starting to pick up hints. Some of these genes are tied to our immune system, to our skin and hair, and perhaps to our metabolism and tolerance for cold weather, all of which might have helped emigrating humans survive in new lands.

“What allowed us to survive came from other species,” said Rasmus Nielsen, an evolutionary biologist at the University of California, Berkeley. “It’s not just noise, it’s a very important substantial part of who we are.”

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The Tibetans: Heights Tolerant Unlike Any Other Human

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Tibetans are more capable than most other people of living at extreme altitudes thanks to a mutation in a gene called EPAS1, which allows them to cope with the oxygen-poor air of the 4,000-meter-high Tibetan Plateau. Now, geneticists have identified the same mutation in the Denisovans, an extinct group of humans with whom our ancestors may have interbred some 30,000-40,000 years ago:

To date, this is still “strongest instance of natural selection documented in a human population”—the EPAS1 mutation is found in 87 percent of Tibetans and just 9 percent of Han Chinese, even though the two groups have been separated for less than 3,000 years. But when the team sequenced EPAS1 in 40 more Tibetans and 40 Han Chinese, they noticed that the Tibetan version is incredibly different to those in other people. It was so different that it couldn’t have gradually arisen in the Tibetan lineage. Instead, it looked like it was inherited from a different group of people. By searching other complete genomes, the team finally found the source: the Denisovans!…

This discovery is all the more astonishing because we still have absolutely no idea what the Denisovans looked like. Denisovan DNA makes up 5 to 7 percent of the genomes of people from the Pacific islands of Melanesia. Much tinier proportions live on in East Asians. And now, we know that some very useful Denisovan DNA lives on in Tibetans.

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The Tibetan plateau is a vast stretch of high-altitude real estate isolated by massive mountain ranges. The scant oxygen at 14,000 feet — roughly 40 percent lower than the concentrations at sea level — makes it a harsh environment. People who move there suffer higher rates of miscarriage, blood clots and stroke on account of the extra red blood cells their bodies produce to feed oxygen-starved tissue. Native Tibetans, however, manage just fine. Despite the meager air, they don’t make as many red blood cells as the rest of us would at those altitudes, which helps to protect their health.

In 2010, scientists discovered that Tibetans owe their tolerance of low oxygen levels in part to an unusual variant in a gene known as EPAS1. About 90 percent of the Tibetan population and a smattering of Han Chinese (who share a recent ancestor with Tibetans) carry the high-altitude variant. But it’s completely absent from a database of 1,000 human genomes from other populations.

In 2014, Nielsen and colleagues found that Tibetans or their ancestors likely acquired the unusual DNA sequence from Denisovans, a group of early humans first described in 2010 that are more closely related to Neanderthals than to us. The unique gene then flourished in those who lived at high altitudes and faded away in descendants who colonized less harsh environments. “That’s one of the most clear-cut examples of how [interbreeding] can lead to adaptation,” said Sriram Sankararaman, a geneticist and computer scientist at the University of California, Los Angeles.

The idea that closely related species can benefit from interbreeding, known in evolutionary terms as adaptive introgression, is not a new one. As a species expands into a new territory, it grapples with a whole new set of challenges — different climate, food, predators and pathogens. Species can adapt through traditional natural selection, in which spontaneous mutations that happen to be helpful gradually spread through the population. But such mutations strike rarely, making it a very slow process. A more expedient option is to mate with species that have already adapted to the region and co-opt some of their helpful DNA. (Species are traditionally defined by their inability to mate with one another, but closely related species often interbreed.)

This phenomenon has been well documented in a number of species, including mice that adopted other species’ tolerance to pesticides and butterflies that appropriated other species’ wing patterning. But it was difficult to study adaptive introgression in humans until the first Neanderthal genome was sequenced in 2010, providing scientists with hominin DNA to compare to our own.

Neanderthals and Denisovans would have been a good source of helpful DNA for our ancestors. They had lived in Europe and Asia for hundreds of thousands of years — enough time to adjust to the cold climate, weak sun and local microbes. “What better way to quickly adapt than to pick up a gene variant from a population that had probably already been there for 300,000 years?” Akey said. Indeed, the Neanderthal and Denisovan genes with the greatest signs of selection in the modern human genome “largely have to do with how humans interact with the environment,” he said.

To find these adaptive segments, scientists search the genomes of contemporary humans for regions of archaic DNA that are either more common or longer than expected. Over time, useless pieces of Neanderthal DNA — those that don’t help the carrier — are likely to be lost. And long sections of archaic DNA are likely to be split into smaller segments unless there is selective pressure to keep them intact.

In 2014, two groups, one led by Akey and the other by David Reich, a geneticist at Harvard Medical School, independently published genetic maps that charted where in our genomes Neanderthal DNA is most likely to be found. To Akey’s surprise, both maps found that the most common adaptive Neanderthal-derived genes are those linked to skin and hair growth. One of the most striking examples is a gene called BNC2, which is linked to skin pigmentation and freckling in Europeans. Nearly 70 percent of Europeans carry the Neanderthal version.

Scientists surmise that BNC2 and other skin genes helped modern humans adapt to northern climates, but it’s not clear exactly how. Skin can have many functions, any one of which might have been helpful. “Maybe skin pigmentation, or wound healing, or pathogen defense, or how much water loss you have in an environment, making you more or less susceptible to dehydration,” Akey said. “So many potential things could be driving this — we don’t know what differences were most important.”

Modern humans can have several different versions of this stretch of DNA. But at least three of the variants appear to have come from archaic humans — two from Neanderthals and one from Denisovans. To figure out what those variants do, Kelso’s team scoured public databases housing reams of genomic and health data. They found that people carrying one of the Neanderthal variants are less likely to be infected with H. pylori, a microbe that causes ulcers, but more likely to suffer from common allergies such as hay fever.

Kelso speculates that this variant might have boosted early humans’ resistance to different kinds of bacteria. That would have helped modern humans as they colonized new territories. Yet this added resistance came at a price. “The trade-off for that was a more sensitive immune system that was more sensitive to nonpathogenic allergens,” said Kelso. But she was careful to point out that this is just a theory. “At this point, we can hypothesize a lot, but we don’t know exactly how this is working.”

Most of the Neanderthal and Denisovan genes found in the modern genome are more mysterious. Scientists have only a vague idea of what these genes do, let alone how the Neanderthal or Denisovan version might have helped our ancestors. “It’s important to understand the biology of these genes better, to understand what selective pressures were driving the changes we see in present-day populations,” Akey said.

A number of studies like Kelso’s are now under way, trying to link Neanderthal and Denisovan variants frequently found in contemporary humans with specific traits, such as body-fat distribution, metabolism or other factors. One study of roughly 28,000 people of European descent, published in Science in February, matched archaic gene variants with data from electronic health records. Overall, Neanderthal variants are linked to higher risk of neurological and psychiatric disorders and lower risk of digestive problems. (That study didn’t focus on adaptive DNA, so it’s unclear how the segments of archaic DNA that show signs of selection affect us today.)

At present, much of the data available for such studies is weighted toward medical problems — most of these databases were designed to find genes linked to diseases such as diabetes or schizophrenia. But a few, such as the UK Biobank, are much broader, storing information on participants’ vision, cognitive test scores, mental health assessments, lung capacity and fitness. Direct-to-consumer genetics companies also have large, diverse data sets. For example, 23andMe analyzes users’ genetics for clues about ancestry, health risk and other sometimes bizarre traits, such as whether they have a sweet tooth or a unibrow.

Of course, not all the DNA we got from Neanderthals and Denisovans was good. The majority was probably detrimental. Indeed, we tend to have less Neanderthal DNA near genes, suggesting that it was weeded out by natural selection over time. Researchers are very interested in these parts of our genomes where archaic DNA is conspicuously absent. “There are some really big places in the genome with no Neanderthal or Denisovan ancestry as far as we can see — some process is purging the archaic material from these regions,” Sankararaman said. “Perhaps they are functionally important for modern humans.”

 

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Re: Genetics: Unlocking Humanity's Past and Future

genetic terrorism briefing

White House science advisors urge CRISPR bioterrorist defense strategy
Should other countries worry?

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Scientific advisers to President Obama warn that the US urgently needs a new biodefense strategy and should regularly brief President-elect Donald Trump on the dangers posed by new technologies like CRISPR, gene therapy, and synthetic DNA, which they say could be coopted by terrorists.

In a letter to the president, the President’s Council of Advisors on Science and Technology (PCAST) urges the creation of a new entity charged with developing a national biodefense strategy within six months.

The council is also urging the president to ask Congress to establish a $2 billion fund to respond to public health emergencies that could be caused by new biotechnologies.

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[T]he council argues that synthetic DNA, gene therapy, and genome-editing technologies like CRISPR open up new possibilities for intentional misuse, such as modifying a virus or bacteria to make it resistant to drugs….

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It will be nearly impossible to monitor all such experiments, [says Todd Kuiken, senior research scholar with the Genetic Engineering and Society Center at North Carolina State University]. But a better national surveillance system that includes detailed information about a germ’s DNA, as is suggested in the letter, could tell government officials whether pathogens involved in disease outbreaks have been engineered or modified.

SOURCE

 

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Re: Genetics: Unlocking Humanity's Past and Future

CRISPR watch

New CRISPR gene-editing tool removes cells' natural undo button

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• New gene editing tool enables modified DNAs to become permanently coded
• Previously, organisms are able to remove DNA codes it recognizes as artificially inserted into it
• New technology promises novel ways to treat diseases and medical disorders—along with more ways sinister forces could misuse it

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The CRISPR-Cas9 gene-editing tool promises to radically change how disease is treated, with potential for tackling muscular dystrophy, HIV and retinal degradation, among others. Now, scientists at Western University in Ontario have edited the editor, adding a new engineered enzyme to CRISPR that can help prevent the target DNA from repairing itself and canceling out the desired changes.

With human trials kicking off recently, CRISPR's power comes from the ability to let scientists swap out sections of DNA, removing unwanted genes like those that might cause cancer or other diseases, and splicing in more helpful ones. Unfortunately, cells have a natural ability to fight back against the "damage" to their DNA molecules, which may undo the benefits.

"The problem with CRISPR is that it will cut DNA, but then DNA-repair will take that cut and stick it back together," says David Edgell, principal investigator of the study. "That means it is regenerating the site that the CRISPR is trying to target, creating a futile cycle. The novelty of our addition is that it stops that regeneration from happening."

The addition in question is an enzyme called I-Tevl, which is combined with Cas9, the DNA-cutting enzyme that gives the CRISPR-Cas9 tool its name. But where Cas9 only makes cuts in one site on the genome, the newly-created TevCas9 cuts in two places, making it much harder for the cell to repair.

As an added bonus, using TevCas9 appears to reduce the chances of unwanted side effects as a result of the cutting, by targeting genes much more directly.

"Because there are two cut-sites, there is less chance that these two sites occur randomly in the genome; much less chance than with just one site," says co-author, Caroline Schild-Poulter. "This remains to be tested, but this is the hope and the expectation."

The research was published in the Proceedings of the National Academy of Sciences.

From: Western University
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Re: Genetics: Unlocking Humanity's Past and Future

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• Partial reprogramming erases cellular markers of aging in mouse and human cells
• Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan
• In vivo reprogramming improves regeneration in 12-month-old wild-type mice​

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Graying hair, crow's feet, an injury that's taking longer to heal than when we were 20—faced with the unmistakable signs of aging, most of us have had a least one fantasy of turning back time. Now, scientists at the Salk Institute have found that intermittent expression of genes normally associated with an embryonic state can reverse the hallmarks of old age.

This approach, which not only prompted human skin cells in a dish to look and behave young again, also resulted in the rejuvenation of mice with a premature aging disease, countering signs of aging and increasing the animals' lifespan by 30 percent. The early-stage work provides insight both into the cellular drivers of aging and possible therapeutic approaches for improving human health and longevity.

"Our study shows that aging may not have to proceed in one single direction," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and senior author of the paper appearing in the December 15, 2016 issue of Cell. "It has plasticity and, with careful modulation, aging might be reversed."

As people in modern societies live longer, their risk of developing age-related diseases goes up. In fact, data shows that the biggest risk factor for heart disease, cancer and neurodegenerative disorders is simply age. One clue to halting or reversing aging lies in the study of cellular reprogramming, a process in which the expression of four genes known as the Yamanaka factors allows scientists to convert any cell into induced pluripotent stem cells (iPSCs). Like embryonic stem calls, iPSCs are capable of dividing indefinitely and becoming any cell type present in our body.

"What we and other stem-cell labs have observed is that when you induce cellular reprogramming, cells look younger," says Alejandro Ocampo, a research associate and first author of the paper. "The next question was whether we could induce this rejuvenation process in a live animal."

WATCH VIDEO IN SEPARATE WINDOW​

While cellular rejuvenation certainly sounds desirable, a process that works for laboratory cells is not necessarily a good idea for an entire organism. For one thing, although rapid cell division is critical in growing embryos, in adults such growth is one of the hallmarks of cancer. For another, having large numbers of cells revert back to embryonic status in an adult could result in organ failure, ultimately leading to death. For these reasons, the Salk team wondered whether they could avoid cancer and improve aging characteristics by inducing the Yamanaka factors for a short period of time.

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Researchers at the Salk Institute in La Jolla, California have discovered a way to turn back the hands of time. Juan Carlos Izpisua Belmonte led this study, published in the journal Cell. Here, elderly mice underwent a new sort of gene therapy for six weeks. Afterward, their injuries healed, their heart health improved, and even their spines were straighter. The mice also lived longer, 30% longer.

Today, we target individual age-related diseases when they spring up. But this study could help us develop a therapy to attack aging itself, and perhaps even target it before it begins taking shape. But such a therapy is at least ten years away, according to Izpisua Belmonte.

Many biologists now believe that the body, specifically the telomeres—the structures at the end of chromosomes, after a certain time simply wear out. Once degradation overtakes us, it’s the beginning of the end. This study strengthens another theory. Over the course of a cell’s life, epigenetic changes occur. This is the activation or depression of certain genes in order to allow the organism to respond better to its environment. Methylation tags are added to activate genes. These changes build up over time, slowing us down, and making us vulnerable to disease.

Though we may add life to years, don’t consider immortality an option, at least not in the near-term. “There are probably still limits that we will face in terms of complete reversal of aging,” Izpisua Belmonte said. “Our focus is not only extension of lifespan but most importantly health-span.” That means adding more healthy years to life, a noble prospect indeed.

The technique employs induced pluripotent stem cells (iPS). These are similar to those which are present in developing embryos. They are important as they can turn into any type of cell in the body. The technique was first used to turn back time on human skin cells, successfully.

By switching around four essential genes, all active inside the womb, scientists were able to turn skin cells into iPS cells. These four genes are known as Yamanaka factors. Scientists have been aware of their potential in anti-aging medicine for some time. In the next leg, researchers used genetically engineered mice who could have their Yamanaka factors manipulated easily, once they were exposed to a certain agent, present in their drinking water.

Since Yamanaka factors reset genes to where they were before regulators came and changed them, researchers believe this strengthens the notion that aging is an accumulation of epigenetic changes. What’s really exciting is that this procedure alters the epigenome itself, rather than having the change the genes of each individual cell.

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To find out, the team turned to a rare genetic disease called progeria. Both mice and humans with progeria show many signs of aging including DNA damage, organ dysfunction and dramatically shortened lifespan. Moreover, the chemical marks on DNA responsible for the regulation of genes and protection of our genome, known as epigenetic marks, are prematurely dysregulated in progeria mice and humans. Importantly, epigenetic marks are modified during cellular reprogramming.

Using skin cells from mice with progeria, the team induced the Yamanaka factors for a short duration. When they examined the cells using standard laboratory methods, the cells showed reversal of multiple aging hallmarks without losing their skin-cell identity.

"In other studies scientists have completely reprogrammed cells all the way back to a stem-cell-like state," says co-first author Pradeep Reddy, also a Salk research associate. "But we show, for the first time, that by expressing these factors for a short duration you can maintain the cell's identity while reversing age-associated hallmarks."

Encouraged by this result, the team used the same short reprogramming method during cyclic periods in live mice with progeria. The results were striking: Compared to untreated mice, the reprogrammed mice looked younger; their cardiovascular and other organ function improved and—most surprising of all—they lived 30 percent longer, yet did not develop cancer. On a cellular level, the animals showed the recovery of molecular aging hallmarks that are affected not only in progeria, but also in normal aging.

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"This work shows that epigenetic changes are at least partially driving aging," says co-first author Paloma Martinez-Redondo, another Salk research associate. "It gives us exciting insights into which pathways could be targeted to delay cellular aging."

Lastly, the Salk scientists turned their efforts to normal, aged mice. In these animals, the cyclic induction of the Yamanaka factors led to improvement in the regeneration capacity of pancreas and muscle. In this case, injured pancreas and muscle healed faster in aged mice that were reprogrammed, indicating a clear improvement in the quality of life by cellular reprogramming.

"Obviously, mice are not humans and we know it will be much more complex to rejuvenate a person," says Izpisua Belmonte. "But this study shows that aging is a very dynamic and plastic process, and therefore will be more amenable to therapeutic interventions than what we previously thought."

The Salk researchers believe that induction of epigenetic changes via chemicals or small molecules may be the most promising approach to achieve rejuvenation in humans. However, they caution that, due to the complexity of aging, these therapies may take up to 10 years to reach clinical trials.

SOURCE

REFERENCES
Scientists are One Step Closer to Reversing the Aging Process Entirely
Scientists take on what was once thought impossible: reversing aging
Cellular reprogramming has been used to reverse ageing in living animals for the first time

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

001

OUT of AFRICA: RECAP


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Let's tie some loose things up with these videos to summarize what the threads about our common African heritage and those of us who carry Neanderthal and Denisovan genes. After this, I'll feature those humans today who have neither Neanderthal or Denisovan genes in them—unless some worthy new developments in the field come up....

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

​What will humans look like in 100 years?
Changing the rules of evolution

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DISCUSSION

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[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

The first baby conceived using DNA from three people to stop mitochondrial disease has been born in Mexico, according to research to be presented at the American Society of Reproductive Medicine conference in Salt Lake City, Utah, next month.

The five-month-old boy was conceived using a technique known as spindle nuclear transfer, where the nucleus of the mother's egg is transplanted into a donor egg with healthy mitochondria which has had its own nucleus removed.

Because mitochondria have their own small amount of DNA, once the egg is fertilised via IVF, the embryo contains the genetic material from three different people.

The technique was used in order to try and stop the baby developing the mitochondrial disease known as Leigh Syndrome.

Leigh syndrome

• A severe neurological disorder, affecting at least one in 40,000 new-born babies.
• Usually becomes apparent during the first year of a child's life.
• First signs include vomiting, diarrhoea and difficulty with swallowing.
• Causes the progressive loss of movement, and deterioration of mental functions.
• Symptoms are linked to the development of patches of damaged tissue which develop in the brain.
• Children with the condition usually die within two to three years, usually because of respiratory failure.
• Mutations in 75 different genes have been linked to the condition.
• Most of those mutations occur in DNA from the nucleus, but in about one in five cases the culprit is found in mitochondrial DNA.

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

You go through life not realizing some things you ever have to question about, much less think of being ever in peril. Take the existence of men: why, all our mores and traditions—religion, especially Christianity (and Judaism and Islam, for that matter) and its Eve-out-of-Adam’s-rib tale—teach us that the primacy of man over woman is beyond any doubt.

Yet biology teaches the exact opposite: a system where all offspring are produced without sex—as in all-female asexual populations—would be far more efficient at reproducing greater numbers of offspring, and since in many species sperm is males' only contribution to reproduction, biologists have long puzzled about why evolutionary selection, known for its ruthless efficiency, allows men to exist….

Thank, then, these British scientists who have just the explanation to arrest the deflation of male ego: males are required for a process known as "sexual selection," which helps the species to ward off disease and avoid extinction. Hey, that is ever so deep a reason...

Populations that clone themselves are entirely female and do not need sex with men to reproduce. As sex requires males, and males do not produce offspring themselves, an entirely clonal population should always reproduce faster than a sexual one.

However, men are necessary to help the health of populations—sex helps mix things up a bit.

Researchers from the University of Stirling have found that populations produced through sexual reproduction could be more than twice as resistant to infectious diseases than those created by cloning.


So there…


Men owe existence to infections

“Infections from parasites could explain why males and men continue to exist,” said Dr Stuart Auld, of the University of Stirling.

The mixing up of genes that occurs through mating allows populations to evolve to adapt to threats, such as rapidly evolving parasites, much more quickly than those created by cloning, which only involves the genes of the mother.

This means that genetic mutations which make a person stronger and ensure the “survival of the fittest” will be passed on more rapidly through sex.

“Mutations can occur at any time, ultimate source of all biological variation on earth. Sex combines them, repackages them, splits them up and sex takes the mutations and amplifies the variations,” Dr. Auld said.



Sex versus cloning
Dr. Auld began looking at the relative merits of sex and cloning because he was puzzled as to why any species would bother spending the huge energy involved in mating when they could simply clone themselves.

“Sex explains the presence of the peacock’s tail, the stag’s antlers and the male bird of paradises elaborate dance. But these use up huge amounts of energy and can come at a high cost. Peacocks draw attention to themselves through their feathers and get eaten by tigers and the tail makes it more difficult for them to fly up a tree. But it attracts mates. It’s a trade off,” Dr Auld said.

His team examined the issue by looking at a waterflea, one of very few organisms that can reproduce both sexually and by cloning.

“By comparing clonal and sexual daughters from the same mothers, we found sexually produce offspring get less sick than their offspring that were produced clonally. The ever-present need to evade disease can explain why sex persists in the natural world in spite of the costs,” said Dr Auld. The research is published in the journal Royal Society Proceedings B.


Hmm, our—men's—purpose now clinging on the thin thread of providing infection protection—which begs the question: what happens to men when science has finally figured all the medical stuff out…?

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

genetics: destroying racial myths
GENETICALLY, RACE DOES NOT EXIST

THERE IS NO LONGER ANY EXCUSE TO IGNORE one of the most popular findings in science in recent years: the recognition that genetically, there is no such thing as race. Nothing in our DNA identifies us as Caucasian, Mongoloid, or Negroid, or lends any support to the idea that any of those classifications might exist at all. No gene or combination of genes is unique to any race. Race, says today's common wisdom, is merely a "social construct" — it is a way we look at each other, make a snap judgement based on some obvious traits, and apply a label. This seems like a simple enough resolution of the question, and is not especially controversial. So why, then, does the question persist?

Humans are a relatively young species, and there is much less diversity among us than among other species. Consider how much chimpanzees look alike to us; and then consider that any two chimpanzees have about twice as many genetic differences between them than do two humans of greatly different size, shape, and color. Genetically, we are the most homogenous of any primate. Turns out that all those perceived differences between us don't go very deep at all. But that hasn't stopped some people from trying to make it seem so.

The classical definition of the races, which you can find repeated all over the Internet, comes from an old German encyclopedia, the Meyers Konversations-Lexikon, 4th edition. It contrasts the skull, face, and nose shapes of Caucasians, Mongoloids, and Negroids. Caucasians, for example, are said to have long, narrow, high noses; Mongoloids have wide, short faces with projecting cheekbones; and Negroids have long skulls with prominent jaws. Reading the descriptions, and living in the melting pot of California, what's clear to me is that I don't really know anyone who matches any Meyers racial description.

But this chasm between today's reality and obsolete racial descriptions is backed up by evidence that's a lot more substantial than my personal observation. In today's science, we don't speak so much of races as we do of populations, loosely defined as a group with a certain frequency of certain alleles relative to others. To understand what that means, let's go through some brief definitions.

An allele is one alternative form of a gene that usually has two possible variations, and usually one is dominant and one is recessive. A familiar example is one difference between Scandinavians and Asians: we're likely to find a lot of the blue-eye alleles in the Scandinavian population, and a lot of the brown-eye alleles in the Asian population. The relative frequency of various alleles in different populations is what makes the populations look distinct from one another. The allele for red hair is found a lot in Ireland. Freckles, cleft chins, dimples, blood type, color blindness, earlobe shape, and countless other traits are all controlled by alleles.

Populations, defined this way, are not distinct from one another. They blend into each other. Populations are not bounded by lines, but by clines, which are gradations. A population as a whole has a certain frequency of alleles, but any given individual is somewhere along a cline, and it is difficult or impossible to tell which population he might be from.

A genotype is your genetic fingerprint. It's the sum of all the inheritable genetic variations that make you an individual unique from everyone else. Your genotype is the dataset that we'd get by sequencing your genome.

Your phenotype, on the other hand, is a broader description. It includes all the observable traits that your genotype has conferred upon you, and also your learned behaviors and other environmental influences. Your phenotype is that combination of nature and nurture that makes you not just what you are, but who you are.

Genotype and phenotype can also apply to a single trait. A person's genotype may include several alleles affecting eye color; his phenotype is the color that finally manifests itself.

It's this difference between genotype and phenotype that has driven some apparent scientific support for racial stereotyping. One of the most dramatic examples was the 1994 book The Bell Curve: Intelligence and Class Structure in American Life. One of the points made in the book was that there are racial differences in intelligence; a point which, it turns out, is indeed supported by the data; but, importantly, only if race did exist. The book triggered enormous controversy, both in favor of and opposed to its conclusions. While the authors argued for a genotypical basis for intelligence, most criticism — and most of today's scientists in the field — would argue for a phenotypical basis. When you're born poor, badly educated, perhaps raised with English as a second language, drop out of school to join a gang — sounds like one or more familiar racial stereotypes, doesn't it? — you are indeed more likely to score badly on an intelligence test. The evidence that we have today suggests that this is due to phenotype, which incorporates environmental pressures such as life experience and education.

Outside of science, the idea of race has, quite obviously, been responsible for a massive proportion of all the bad things in human history. Nearly everyone wants to discard it completely, but we can't, because we find we still have needs for it. Race comes into play when we design programs intended to undo some of the harm that was done to certain populations. But perhaps least controversially, and most complicated, is the fact that we still need it for the medical and biological sciences.

A fundamental difference between race and ancestry is that ancestry is a bottom-up process, while race is a top-down classification. Except for their immediate siblings, every person on Earth has a different ancestry, and each of us has become — through countless generations — increasingly diversified from everyone else. Our ancestry includes all that we are, and it is unique to us. Race, however, discounts the intricacies of ancestry and instead takes a single superficial glance at a few basic traits, then rubber stamps us with one of a very few categories. Race is a label that dismisses a massive amount of data, so it would seem to be an idea that's not of very much use to biologists.

Yet it is still used, and used a lot. The idea of race has hung on for so long in biological circles because many diseases are highly correlated with race. We had to understand why this is, in order to understand the disease and develop a way to fight it. So, even though it was politically incorrect, studying cystic fibrosis in "white people" or sickle cell anemia in "black people" made a certain amount of sense. Researchers and even healthcare providers still often ask patients to identify themselves by race, because the idea has always been that it's a useful predictor of susceptibility to certain diseases, or of reaction to certain treatments.

This is largely wrong, but it isn't entirely wrong. People who appear to be of the same race probably do share many of the same alleles, thus they're also more likely to share the same disease-related markers. This is often the case with people from the center of a population, such as people with a deep Chinese heritage whose ancestors have lived in the same area for a thousand years. It's far less likely to be the case in a country like the United States, where everyone's ancestors came from populations all over the globe, each of whom followed a different braid of intermarriage to get there. So the likelihood is far less, but even people in the United States with similar physical appearances are more likely to share disease markers than are two people with different racial identifications.

This limited utility of a "race" classification in biology is becoming more limited with each generation, as populations become increasingly blended. About all it has going for it is convenience due to nearly everyone's ability to self-report. But the convenience of access to bad data is not necessarily a merit.

The problem is that we don't always have access to good data. Many of the alleles related to diseases haven't yet been identified, so there are still a lot of cases where we can't look at someone's genotype and know their susceptibility to a certain disease. But in some of these cases, we can still look at them and say something like "Hmmm, you look Asian, you'll probably react well to this particular drug." It might not be right in this particular person's case, but unless we have a family history that gives us better information, it might well be all we have to go on.

In some ideal future, we may have a Star Trek tricorder paired with a fully grokked human genome, and we'll immediately know everything that genomics can tell a medical professional about any person. That day will come, but it is not here yet, not by a long shot.

So where does all of this leave us? With a reminder that genetics is an exciting field that should tempt any student. Even though the human genome has been completed, there's a lot we still don't know, and indeed including much that may never be known. Too much remains hidden in our genes for the biological sciences to completely abandon socially-derived categories for human beings. Race, however, brings little to the table; especially in a globalized populace, a visual phenotyping is past the point of utility in determining genotype. Population and ancestry are far more useful than race, but they are not always evident or available. Given the lack of a Star Trek medical tricorder, the simple fact is that we don't have a solution yet. Biologists and geneticists must struggle on with inadequate tools.

Race, from a sociological perspective, still has relevance when we seek to help everyone achieve their potential. Although fraught with shortcomings, it still has an awkward place in some biological sciences. We can't ignore the fact that the very idea of race has had devastating and offensive consequences to our history; that's quite an accomplishment for something that provably does not exist. We find ourselves mired in a self-defeating bog of damned-if-you-do, damned-if-you-don't. The problem is not one with a tidy solution. But it is not a hopeless situation. With each passing day, the usefulness of race in any science diminishes, and then it will have no place at all. It will, ultimately, find itself in the landfill of discarded human follies where it so rightly belongs.

There is no such thing as race

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

It's not the genes. It's the optical illusion, so say experts finally about people dying to have those killer eye colors. Well...!

Everyone has brown eyes and there are no blue or green color eyes in a real sense, an optometrist has said. There is only one pigment for eye color—brown. Eye colors like blue, green, hazel, etc., are what people might call an optical illusion. Pigments in our body are determined by something called melanin.

“Everyone has melanin in the iris of their eye, and the amount that they have determines their eye color,” said Dr. Gary Heiting, a licensed optometrist and senior editor of the eye care website All About Vision. “There’s really only (this) one type of pigment.”

Pigments in our body are determined by something call melanin. Irises are made up of a miniature version of melanin called melanocytes, which only come in one color, brown, CNN reported. Even though all eyes are technically brown, the amount of melanocytes varies from person to person. There’s really only one “shade” of melanin — and it’s brown!, Heiting said.

However, people with lighter eyes have less melanocytes, allowing light to be more easily absorbed and reflected, making their eyes appear lighter in color. Brown-eyed people have more melanin, less light. The opposite is true for people with “blue” eyes. Those with less melanocytes can not absorb as much light, so more light is reflected back out of the eye, Heiting was quoted as saying by the report.

This is called scattering — and when light is scattered, it reflects back at shorter wavelengths. On the color spectrum, shorter light wavelengths correspond with the color blue.

So there ... MELANIN.

Still ... those blue eyes....

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

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In a previous post, I mentioned how is it that men are still around when women could procreate by themselves. Turned out I spoke too soon: there is now an equalizer in this respect, one that scientists from all over are urging nations to begin contemplating the legal minefield that would surround it. What I’m talking about is that women are not necessary for reproduction either. For clarity, let’s state what that means: a single man or a single woman can procreate alone. Read that again and think about what that means for humanity.

The technology is called in vitro gametogenesis. It involves turning any human cell—the skin, for example, and as simply by quickly applying a swab in the cheek—and turning one sample into egg cell, and another sample into sperm cell.

The technology is not perfected in humans yet, but it is under a lively ongoing activity. It has been perfected in mice, however, and scientists are unequivocal in telling us that it would be perfected in humans shortly too.

Not only that, the technology allows incorporating genetic materials from multiple sources: three men or three women, for example, or from multiple men and women at the same time, ensuring that the child-to-be would get the best genetic materials from those sources.

So picture the possible scenarios based on this technology:

• Babies conceived from a single parent, either a woman or a man
• Same-sex couples finally having babies derived from their own genetic makeup
• “multiplex” parenting, where groups of more than two individuals procreate together, producing children who are the genetic progeny of them all
• the technique could allow women whose fertility has been wiped out by cancer drugs or radiotherapy to have their own healthy children
• aid the preservation of endangered species, since it avoids the need to recover eggs.
• Governments or private interests harvesting superior embryos from multiple sources and producing superior babies to be raised as super soldiers or for any other sinister purposes

So back to the question: are you ready for this?

ARE WE READY FOR THIS?

 

[Stormer0628]

Re: Genetics: Unlocking Humanity's Past and Future

Doctors in Ukraine have announced a world-first, with a 'three-parent' baby being born to an infertile couple.

The child, born on January 5, is the result of new medical techniques that enable a baby to be conceived with DNA from three adults. But the procedure remains controversial, and while it's been approved in the UK as a way of avoiding genetic diseases, this is the first time it's been used as a remedy for infertility.

A team led by fertility researcher Valery Zukin at the Nadiya clinic in Kiev helped the baby's parents to conceive by using an in vitro fertilisation (IVF) technique called pronuclear transfer.

In this case, the baby's mother had been trying to have a child for a decade, and had been through four unsuccessful rounds of conventional IVF.

While her embryos were fertilized successfully each time, they stopped growing before they could be implanted in her womb—a condition known as an embryonic arrest.

To get around this happening, Zukin and his team made a hybrid embryo, fertilising the mother's egg with her partner's sperm, and then transferring the resulting pronucleus into an embryo from a donor female.

That embryo is then implanted in the mother's womb, resulting in a baby with the genetic identity of both parents, along with the mitochondrial DNA from the donor.

"It's like the opening of a new era," Zukin told Oliver Moody at The Times.

"Before, we could only increase the selection of embryos. But for us this moment opens up the possibility of augmenting embryos."

Mitochondrial donation, which encompasses the pronuclear transfer technique, was legalised in the UK in 2015 for use in a narrow range of circumstances where the mother's mitochondrial DNA is unhealthy, and can lead to children developing genetic diseases.

Then, last year, the procedure was used for the first time to create a 'three-parent baby' in Mexico (previously featured in this thread too).

In that case, the mother had Leigh disease, a genetic disorder affecting the nervous system, which she didn't want to pass down through her own mitochondrial DNA.

But the use of the technique as a remedy for infertility complications is decidedly controversial, as safety issues around mitochondrial donation are still being explored, and the prospect of it being carried out in private, unregulated clinics has some scientists concerned.

Assisted pregnancies and new techniques in human reproduction are ushering in an unheard of development for humanity. The obvious critical question is: where are these leading us?

SOURCE

 

[Stormer0628]

The world of genetics appears to be turning in new amazing works faster than many people could process them. I have a backlog of articles waiting, but this kind of thing just begs to be first. Sometime back, I featured how scientists have created an entirely alien life form made of silicon-carbon bonds. And now this.

THIS refers to new organisms that have been formed using the first ever 6-letter genetic code. For those who have not been paying close attention to their high school biology class, every living thing on Earth is formed according to a DNA code made up of four bases (represented by the letters G, T, C and A). These modified life form—an E. coli bacteria—carries an entirely new type of DNA, with two additional DNA bases, X and Y, nestled in their genetic code.

The team, led by Floyd Romesberg from the Scripps Research Institute in California, engineered synthetic nucleotides - molecules that serve as the building blocks of DNA and RNA - to create an additional base pair, and they’ve successfully inserted this into the E. coli’s genetic code.

Now we have the world’s first semi-synthetic organism, with a genetic code made up of two natural base pairs and an additional 'alien' base pair, and Romesberg and his team suspect that this is just the beginning for this new form of life.

"With the virtually unrestricted ability to maintain increased information, the optimised semi-synthetic organism now provides a suitable platform [to] ... create organisms with wholly unnatural attributes and traits not found elsewhere in nature," the researchers report.

"This semi-synthetic organism constitutes a stable form of semi-synthetic life, and lays the foundation for efforts to impart life with new forms and functions."

Back in 2014, the team announced that they had successfully engineered a synthetic DNA base pair - made from molecules referred to as X and Y - and it could be inserted into a living organism.

Since then, they’ve been working on getting their modified E. coli bacteria to not only take the synthetic base pair into their DNA code, but hold onto it for their entire lifespan.

Initially, the engineered bacteria were weak and sickly, and would die soon after they received their new base pair, because they couldn’t hold onto it as they divided.

"Your genome isn't just stable for a day," says Romesberg. "Your genome has to be stable for the scale of your lifetime. If the semisynthetic organism is going to really be an organism, it has to be able to stably maintain that information."

Over the next couple of years, the team devised three methods to engineer a new version of the E. coli bacteria that would hold onto their new base pair indefinitely, allowing them to live normal, healthy lives.

The first step was to build a better version of a tool called a nucleotide transporter, which transports pieces of the synthetic base pair into the bacteria’s DNA, and inserts it into the right place in the genetic code.

"The transporter was used in the 2014 study, but it made the semisynthetic organism very sick," explains one of the team, Yorke Zhang.

Once they’d altered the transporter to be less toxic, the bacteria no longer had an adverse reaction to it.

Next, they changed the molecule they’d originally used to make the Y base, and found that it could be more easily recognised by enzymes in the bacteria that synthesise DNA molecules during DNA replication.

Finally, the team used the revolutionary gene-editing tool, CRISPR-Cas9 to engineer E. coli that don’t register the X and Y molecules as a foreign invader.

The researchers now report that the engineered E. coli are healthy, more autonomous, and able to store the increased information of the new synthetic base pair indefinitely.

"We've made this semisynthetic organism more life-like," said Romesberg.

If all of this is sounding slightly terrifying to you, there's been plenty of concern around the potential impact that this kind of technology could have.

Back in 2014, Jim Thomas of the ETC Group, a Canadian organisation that aims to address the socioeconomic and ecological issues surrounding new technologies, told the New York Times:

"The arrival of this unprecedented 'alien' life form could in time have far-reaching ethical, legal, and regulatory implications. While synthetic biologists invent new ways to monkey with the fundamentals of life, governments haven’t even been able to cobble together the basics of oversight, assessment or regulation for this surging field."​

And that was when the bacteria were barely even functioning.

But Romesberg says there's no need for concern just yet, because for one, the synthetic base pair is useless. It can't be read and processed into something of value by the bacteria - it's just a proof-of-concept that we can get a life form to take on 'alien' bases and keep them.

The next step would be to insert a base pair that is actually readable, and then the bacteria could really do something with it.

The other reason we don't need to be freaking out, says Romesberg, is that these molecules have not been designed to work at all in complex organisms, and seeing as they're like nothing found in nature, there's little chance that this could get wildly out of hand.

"[E]volution works by starting with something close, and then changing what it can do in small steps," Romesberg told Ian Sample at The Guardian.

"Our X and Y are unlike natural DNA, so nature has nothing close to start with. We have shown many times that when you do not provide X and Y, the cells die, every time."

Time will tell if he's right, but there's no question that the team is going to continue improving on the technique in the hopes of engineering bacteria that can produce new kinds of proteins that can be used in the medicines and materials of the future.

As Romesberg asserts, "This will blow open what we can do with proteins."

The research has been published in Proceedings of the National Academy of Sciences.

 

[Stormer0628]

Hailed as possible treatment for cancer, two infants with leukemia are now in remission, thanks to a world-first treatment that uses genetically engineered T-cells from healthy donors.

The patients, from UK, were first given the treatment back in 2015, after chemotherapy failed to show results. Now, after two years, both remain cancer-free.

If similar success is seen in future trials, the treatment could offer a cheap and universal way to fight cancers, without needing to tailor T-cells specifically for different patients.

"This application of an emerging technology has provided a demonstration of the potential of gene-editing strategies for engineered cell therapies, albeit with a clinical experience limited to two infants," the team from London’s Great Ormond Street Hospital writes.

The infants, who were 11 months and 16 months when they started the new treatment, had previously undergone chemotherapy to treat leukemia. Both treatments failed to show any results, and their parents were told they should prepare for the worst.

With no other options, doctors at London’s Great Ormond Street Hospital tried a new procedure: injecting the infants with genetically engineered T-cells - known as chimeric antigen receptor, or CAR-T cells—taken from healthy donors.

"I didn't want to go down that road, I'd rather that she tried something new and I took the gamble," Ashleigh Richards, father of one of the infants, Layla Richards (pictured above), told James Gallagher at the BBC shortly after the treatments in 2015.

"And this is her today standing laughing and giggling, she was so weak before this treatment, it was horrible and I'm just thankful for this opportunity."

T-cells are a type of white blood cell that can attack and destroy infected cells within the body, including cancer cells.

Unfortunately, the body's T-cells aren't always up to the task of finding and destroying all cancerous cells, especially if they're growing particularly fast.

There have been attempts in the past to improve T-cells' ability specifically seek and destroy cancer cells.

One of the most successful ways involves doctors taking a patient’s own T-cells, genetically engineering them to better target errant cells, and placing them back in the body, where they reproduce and form a more aggressive army.

But not all patients have enough healthy cells for this to work.

This new treatment, on the other hand, doesn’t require a patient’s own T-cells, meaning doctors could soon have genetically engineered treatments ready to be implemented as soon as cancer is diagnosed, instead of having to wait for the patient’s own T-cells to be engineered.

"We're in a wonderful place compared to where we were five months ago, but that doesn't mean cure," team member Paul Veys from University College London told the BBC back in 2015.

"The only way we will find out if this is a cure is by waiting that one or two years, but even having got this far from where we were is a major, major step."

It has now been one to two years, and both children are still in remission, suggesting that the treatment has worked so far.

It’s important to note that the treatment has only been performed on two patients, so there will need to be more successful trials involving a much larger group of patients before the treatment is widely available for other patients.

But it’s exciting to see the results so far, particularly when it means saving the lives of two babies.

Besides the treatment's apparent success, having an off-the-shelf treatment would be a whole lot cheaper than genetically engineering each patient’s own T-cells.

This new process would involve using the blood of donors to create large batches of CAR-T that could be frozen and given out in doses.

"We estimate the cost to manufacture a dose would be about US$4,000," CAR-T developer Julianne Smith, from a biopharmaceutical company called Cellectis that develops immunotherapies for cancer, told MIT Technology Review.

Smith, who was not involved in the research, says using a patient’s own T-cells costs roughly US$50,000 a pop, making the new treatment far more affordable.

Hopefully, as the research continues, more doctors will test the team’s treatment. If successful, the treatment could see use in hospitals all around the world, but only time will tell.

The team’s work has been published in Science Translational Medicine.

source

 

[rueryuzaki]

^ - This should be on the Academics Thread.
What do you think?

 

[Stormer0628]

^ That would redouble the work—and you know how onerous that would be for yours truly.

Anyway, my main purpose for this thread is to raise people's general awareness of how genetics today challenges what we perceive to be the prevailing culture, traditions, social perceptions about what is still to be treated as natural or normal with regards human biology. Genetics, along with intense works in AI, materials science, and a host of others threatens to explode in our faces in the next decades, unless we address them now to cushion the "culture shock," as my favorite futurist, Alvin Toffler (RIP) would say.

There are just so many things going on right now I can't even seem to keep up posting the latest happenings here.

I thought about doing another thread for the latest in sciences and technology that all point to a threshold where humans really have to choose which way to go, all of them disrupting what we all view as "normal" in the way of thousand-year-old culture and traditions. Never before are these human artefacts facing such disruptive challenges left and right. It's exciting but troublesome at the same time.