Moving Toward a Brave New World

In Aldous Huxley's classic 1932 novel Brave New World, we are introduced to a future world of universal genetically engineered humans. Each person's destiny is precisely and genetically determined in the laboratory before birth, so as to promote harmony in the perfect society. "A place for everyone, and everyone in his place," would be an understated description of the brave new society.

Brave New World (narrated by author) An international team of researchers from MIT, Harvard, Tsinghua University, Columbia University, and the Rockefeller University, have taken a significant step toward Brave New World style complex genomic editing. Now scientists can efficiently add and delete genetic segments over multiple areas of the genome, simultaneously. The scientific world of genetic engineering is unlikely to ever be the same again.

Precise genome editing would have, the authors say, powerful applications across basic science, biotechnology and medicine. The technology, based on a bacterial defense system against viruses, could offer an easy-to-use, less-expensive way to engineer organisms that produce biofuels, to design animal models to study human disease, and to develop new therapies, among other potential applications.

They further note that it could be used to treat human diseases, either inserting missing or dysfunctional genes, or removing harmful genetic elements with much more precision than any available techniques.

...Making use of naturally occurring bacterial protein-RNA systems that recognize and snip viral DNA, the researchers created DNA-editing complexes that include a nuclease enzyme, Cas9, bound to short RNA sequences. These sequences can be designed to target specific locations in the genome; when they encounter a match, the Cas9 nuclease cuts the DNA.

And each of the RNA segments can target a different sequence. “That’s the beauty of this—you can easily program a nuclease to target one or more positions in the genome,” Zhang says, noting that it can be used either to disrupt the function of a gene or to replace it with a new one. To replace the gene, the researchers must also add a DNA template for the new gene, which would be copied into the genome after the DNA is cut.

The method is also very precise... _More at GenEngNews

MIT News Release on story

Among other possible applications, this system could be used to design new therapies for diseases such as Huntington’s disease, which appears to be caused by a single abnormal gene. Clinical trials that use zinc finger nucleases to disable genes are now under way, and the new technology could offer a more efficient alternative.

The system might also be useful for treating HIV by removing patients’ lymphocytes and mutating the CCR5 receptor, through which the virus enters cells. After being put back in the patient, such cells would resist infection.

This approach could also make it easier to study human disease by inducing specific mutations in human stem cells. “Using this genome editing system, you can very systematically put in individual mutations and differentiate the stem cells into neurons or cardiomyocytes and see how the mutations alter the biology of the cells,” Zhang says. _MIT

In Huxley's Brave New World, human society is intentionally stratified by genetically programmed aptitude.

Brave New World is a benevolent dictatorship: a static, efficient, totalitarian welfare-state. There is no war, poverty or crime. Society is stratified by genetically-predestined caste. Intellectually superior Alphas are the top-dogs. Servile, purposely brain-damaged Gammas, Deltas and Epsilons toil away at the bottom. The lower orders are necessary in BNW because Alphas - even soma-fuelled Alphas - could allegedly never be happy doing menial jobs. _http://www.huxley.net/

But in the developing Brave New World of genetic engineering, everyone will want to be an Alpha.

It will be many years before genome editing techniques are reliable enough to use routinely in humans. But that will not prevent them from being used experimentally on political prisoners, for example, inside totalitarian states. And wouldn't it be ironic if the first genetically designed super-intelligent human turned out to be "an enemy of the state?"

Obscure developments in out of the way laboratories can have profound and widespread effects on the human world. Watch closely, and always consider your options.

Another Reason Why You are Not a Chimp

U. Toronto

Humans and chimpanzees share remarkably similar sets of genes.  When measured conventionally, the genes of humans and the genes of chimps are 99% alike.   And yet, chimps do not build cities, do not publish encyclopedias, and do not launch spaceships to Mars and beyond.


Two recent studies:

N. L. Barbosa-Morais et al., “The Evolutionary Landscape of alternative splicing in vertebrate species,” Science, 388, 1587-93, 2012.

J. Merkin et al., “Evolutionary dynamics of gene and isoform regulation in mammalian tissues,”Science, 388, 1593-99, 2012.

provide new information on how two species with very similar DNA patterns can develop so differently in the real world.

The studies from MIT and the University of Toronto, reveal the remarkable degree of difference alternative gene splicing between species -- resulting in distinctly different proteins from the same gene.

“It was somewhat generally assumed that splicing differences that you see between brain and muscle in the mouse would be similar between brain and muscle in the human,” said Donny Licatalosi, professor of RNA molecular biology at Case Western Reserve University in Cleveland, Ohio, who did not participate in the studies, “but what both of these studies are showing is that is not the case. There is a large amount of species-specific alternative splicing.”

...“how do physical and behavioral differences arise if we have a very similar set of genes to that of the mouse, chicken, or frog?” said Ben Blencowe, a cell and molecular biology professor at the University of Toronto, who led one of the studies. A commonly discussed mechanism was variable levels of gene expression, but both Blencowe and Chris Burge, biology and biological engineering professor at Massachusetts Institute of Technology and lead author of the second paper, found that gene expression is relatively conserved among species.

...To assess alternative splicing patterns as well as transcription levels, both groups performed high-throughput sequencing of messenger RNA. They extracted RNA from a large array of organs of different vertebrate species, including frogs, chickens, primates, and humans. “It’s a massive amount of data,” said Cooper.

Blencowe’s team showed that the species-specific alternative splicing changes tended to be driven by differences in the transcripts themselves, which carry a splicing code that guides the splicing machinery—rather than differences in the splicing machinery. For example, human transcripts expressed in mouse cells exhibited human, not mouse, splicing patterns, despite being spliced by mouse machinery.

“These are very important papers that provide for the first time a large-scale view of the evolution of alternative splicing in vertebrates,” said Brent Graveley, professor of genetics and developmental biology at the University of Connecticut, who was not involved in the research. “They demonstrate how dramatically rapidly alternative splicing evolves, and suggest that it might play a role in speciation.”

The incredible capacity for alternative splicing could enable cells to try-out new versions of proteins without risking the complete loss of the originals, said Burge. Of course, if a new version then offers an advantage, the associated sequence changes to the splicing code will be selected for. “It is certainly an attractive model, and we think it is what’s going on,” said Burge. _TheScientist

This remarkably rapid and competitive evolutionary activity is taking place within each cell of almost every tissue inside your body.

Not only does this epigenetic process provide more reasons for differences between species, but it also likely provides more reasons for differences between sub-species. It will probably also eventually reveal significant differences in gene expression between identical twins.

A number of other genetic and epigenetic processes such as copy number variants, transposable elements, non-coding RNAs, non-coding DNAs, unique mutations (each person has about 100 unique mutations in his genome), etc. -- and more to be discovered -- have already provided us with reasons why two individuals with very similar DNA can easily develop significant differences in gene expression.

The alternative splicing mechanisms being elaborated in the two studies above, provide another very powerful source of difference in gene expression -- not only between individuals, but also between body tissues within the same individual. This evolutionary mechanism even introduces differences in gene expression between different cells of the same tissue type.

Biology just keeps getting more and more interesting all the time.

Oh, Those Violent Genes! Genetic Landscapes of Violence

There are neighborhoods that you know to avoid, if you want to keep your wallet, your vehicle, your life, and any loved ones who accompany you. Likewise, there are entire cities, countries, and regions of the world which intelligent people will only visit for very good reason -- accompanied by ample protection.

If one makes the association between the human makeup of such neighborhoods, cities, countries -- and the people who inhabit those places -- one is apt to be labeled a "racist" in the worlds of politically correct groupthink.

But when the modern scientific worlds of genetics and cognitive science come together and declare an association between particular gene sets, and specific types of violent behaviours, intelligent people are given a glimpse behind the curtain of political correctness, into the grist and blood of an important underlying reality.

Flow Chart of Violence

The flow chart of violence above is taken from the article "Genes for susceptibility to violence." It provides a glimpse at some of the different factors which may contribute to the decision (conscious or unconscious) to commit violent acts. The MAO-L genotype refers to the specific monoamine oxidase A (MAO-A) promoter variant which is at least 10 times more common in people of African descent than in most other population groups, and which seems to predispose to both violence and antisocial disorders.

The MAO-L genotype is not the only gene variant which may predispose to violent behaviours, as you can see below:

Natural Born Killers

The table above looks at a number of gene variants which have been associated with violent and other antisocial behaviours. It was taken from an article first published in : Aggression and Violent Behavior 14 (2009) 286–294.

The full set of genetic factors which play into violent behaviour will not be compiled for quite some time yet. Since we have barely discovered the underlying genetic foundations of impulse control, intelligence, executive function, cognitive assessment of threat, susceptibility to fear conditioning, etc., it will take a number of decades to fill in the outlines -- and much more to fill in the gaps.

Natural Born Killers

The excerpt above comes from the summary of the article "Natural Born Killers: The Genetic Origins of Extreme Violence." It is meant to help explain the difference in rates of violence between men and women. The reference to "impulse control" makes an important point: Even humans who are genetically predisposed to anti-social behaviours can exert self-control to abort impulses toward violent behaviours before they are carried out.

And since "impulse control" itself is largely genetically determined, we see that if an individual is genetically inclined to harbour violent impulses -- and is additionally genetically inclined to have low impulse control -- the likelihood of that person exhibiting violent behaviours is much higher than in a person who exhibited only one of the two genetically determined traits.

Parenthetically, blacks typically display lower levels of impulse control than other population groups.

Catalyst Model of Antisocial Behaviours

The image above was first published in The Journal of Social Psychology, 2010, 150(2), 160–180. PDF download of article.

The catalyst model of violence was devised by violence researcher Christopher Ferguson. It attempts to illustrate the multiple factors -- genetic and environmental -- which come together to generate violent and anti-social behaviours.

The image suggests a one-way flow from predispositions on the left, to violent behaviours on the image far right. But the actual processes involved -- genetic, emotional/cognitive, and environmental -- are far more complex, with multiple circular feedback loops interacting with each other.

If one looks at the geographical map of violent crime, it is easy to infer that genetic factors -- probably many genetic factors -- interact to cause higher rates of violence among African-derived populations.

Blacks have higher genetic prevalence of some of the factors that predispose to impulsive violence, are genetically inclined to have lesser control of these impulses -- both in terms of executive function and IQ. As the complex components of violence are further uncovered, we will learn more about the reasons for the large discrepancies in rates of violence between African-derived populations, and other human populations.

For although the PC groupthink police will tell you that it is racist to think about such things, in the real world understanding these differences may save your life, and the lives of people you care about.

Humans and Apes: What a Difference a Gene Makes

It seems like miR-941 came around after humans evolved from apes and at just the right moment to give humans a real edge over other mammals, some time between six and one million years ago. This was when we as a species were really out there making strides like the genetic champions we are. _geekosystem

University of Edinburgh researchers have identified a gene that is carried only by humans, and may have assisted humanity's ascent into the realm of language, global civilisation, and terminal angst. Their findings were published in Nature Communications.

Genius Chimp or Dunder Man?

The gene, called miR-941, is carried only by humans and it appeared after humans evolved from apes and played a crucial role in human brain development and could shed light on how we learned to use tools and language...

...Scientists led by Dr Martin Taylor at the Institute of Genetics and Molecular Medicine showed that miR-941 had an important part in the development of the human brain and can even help explain how we acquire language and learn to use tools.

This new gene is the first known gene to be found in humans and not in apes. According to the team, it appears to have a certain purpose in the human body.

The researchers analysed 11 different species of mammals, such as gorillas, chimpanzees, rats and mice, and then compared them to the human genome in order to look for variations. _From Apes to Men

Interestingly, miR-941 is thought to have arisen out of non-coding DNA -- or "junk DNA." If so, a lot of proud people will need to downgrade their family lineages in the light of these findings.

It is known that most differences between species occur as a result of changes to existing genes, or the duplication and deletion of genes. But scientists say this gene emerged fully functional out of non-coding genetic material, previously termed "junk DNA", in a startlingly brief interval of evolutionary time. Until now, it has been remarkably difficult to see this process in action. _MXP

The flood of new information in genetics is overwhelming the old theories. Smarter humans are desperately needed. Perhaps another new gene may emerge "fully functional" out of the junk DNA, to give us a boost?

HMGA2 New Gene Candidate for Higher IQ

More 16 April 2012: 3 related studies in Nature Genetics

Joshua C Bis et al. Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nature Genetics, 2012; DOI: 10.1038/ng.2237

M Arfan Ikram et al. Common variants at 6q22 and 17q21 are associated with intracranial volume. Nature Genetics, 2012; DOI: 10.1038/ng.2245

Jason L Stein et al. Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 2012; DOI: 10.1038/ng.2250

_Source: Sciencedaily

An international team of scientists, including reasearchers from the US and the UK, have discovered a gene that is linked to both larger brain size and higher IQ.

A variant of this gene "can tilt the scales in favour of a higher intelligence", study leader Paul Thompson told AFP, stressing though that genetic blessings were not the only factor in brainpower.

Searching for a genetic explanation for brain disease, the scientists stumbled upon a minute variant in a gene called HMGA2 among people who had larger brains and scored higher on standardised IQ tests.

Thompson dubbed it "an intelligence gene" and said it was likely that many more such genes were yet to be discovered.

The variant occurs on HMGA2 where there is just a single change in the permutation of the four "letters" of the genetic code.

... the researchers found that people with a double "C" and no "T" in a specific section of the HMGA2 gene had bigger brains on average.

"It is a strange result, you wouldn't think that something as simple as one small change in the genetic code could explain differences in intelligence worldwide," said Thompson, a neurologist at the University of California at Los Angeles.

The discovery came in a study of brain scans and DNA samples from more than 20,000 people from North America, Europe and Australia, of European ancestry.

People who received two Cs from their parents, a quarter of the population, scored on average 1.3 points higher than the next group -- half of the population with only one C in this section of the gene.

The last quarter of people, with no Cs, scored another 1.3 points lower. "The effect is small," said Thompson, but "would be noticeable on a (IQ) test ... (it) may mean you get a couple more questions correct.

The research, published in Nature Genetics, was conducted by more than 200 scientists from 100 institutions worldwide, working together on a project called Enigma.

Thompson said other studies have implicated some genes in IQ, but this was the first to link a common gene to brain size.

The team found that every T in place of a C represented a 0.6 percent smaller brain -- equal to more than a year's worth of brain loss through the normal ageing process.

Asked to comment on the research, Tom Hartley, a psychologist at Britain's University of York said he was "a little wary of thinking in terms of a gene for intelligence.

"There are undoubtedly a lot of things that have to work properly in order to get a good score on an IQ test, if any of these go wrong the score will be worse." But he said it was "fascinating" to find that such small genetic changes could affect the size of critical structures such as the hippocampus, the brain's memory centre.

"Given the importance of the hippocampus in disorders such as Alzheimer's disease these could turn out to be very significant findings," said Hartley._AFP

Nature Genetics article preview and figures

More from Eurekalert

More

In other IQ news, high IQ has been linked to high levels of worry.

No one expects human intelligence to be controlled by only one, or just a few, genes. But the anatomy of the brain as well as the physiological processes in the brain that underlie intelligence, are all at least partially determined and controlled by genetic factors. The wealth of discoveries over the past half century, which tie differences in genes to differences in intelligence, are likely to grow richer as the tools of exploration and discovery become more powerful and specific.

Humans, Apes, Addicts, and Microbes: Their Common Thread

The common thread that links life on Earth is the thin thread of DNA that coils, circles, and works its way through the generations, through the species, changing the face of the planet as it evolves.

Economist
Our brains are formed by our genes, working through the environment. Some genes control an entire platoon of other genes. The genes that determine how our brains grow and function are still evolving. If these "commander" genes evolve, remarkable changes can occur over a fairly short time span. The human species appears to be changing on a more rapid time scale than most scientists are willing to accept.

...human beings have suites of genes that probably cause their brains to be “plastic” and thus receptive to change far longer (to the age of about five) than is true for chimps or monkeys (whose brains are plastic for less than a year after birth). Moreover, Dr Khaitovich was able to work out how the expression of these modules of genes was co-ordinated, by looking at the switches, known as transcription factors, that turn them on and off.

Indeed, by comparing modern genomes with their discoveries about Neanderthals Dr Paabo’s group has found that the regulatory process for one of the modules came into existence after the modern human and Neanderthal lines separated from one another, about 300,000 years ago. _Economist

Of course, it does no good to have brains that are more plastic, if the caregivers of young children do not take advantage of that period of plasticity to give the children skills, competencies, wisdom, and knowledge that will serve them well throughout their lives.

Some people may be born at a tremendous disadvantage, genetically speaking. Addictive and criminal behaviour appear to be at least partially heritable. Societies deal with these problems in different ways. There is always room for improvement -- beginning with the acknowledgement of the genetic component.

Humans have turned a corner in understanding their own genetics. They can now re-program the genes of living humans, and are on the verge of re-programming the genes of embryos and zygotes. Artificial evolution, in other words.

Humans are also making progress toward understanding the complex genetics of their environments -- the microbial world in which they are immersed. We live in microbial soup, which is quite difficult to sort out with the old genetic tools that required culturing organisms before their genomes could be sequenced.

Now, scientists can extract individual genomes out of the common slurry, and sequence these mystery guests.

To extract individual genomes, Armbrust’s PhD student Vaughn Iverson exploited skills that had he gained as a computer scientist designing video compression technology at Intel in Portland, Oregon. He developed a computational method to break the stitched metagenome into chunks that could be separated into different types of organisms. He was then able to assemble the complete genome of Euryarchaeota, even though it was rare within the sample. He plans to release the software over the next six months.

It’s a different tack from that taken by early marine metagenomics efforts, which began in earnest with Craig Venter’s Global Ocean Sampling effort in 20032. “Our survey offered a broad-stroke picture of microbial diversity and the dominant players in the world’s oceans,” says Kenneth Nealson, director of the microbial and environmental genomics group at the J. Craig Venter Institute in San Diego, California. “This clever approach demonstrates that they can pull out the sequence of uncultured organisms — information we need to get a clue as to how microbes share limiting resources in the ocean.” _Nature

We finally understand that it is necessary to understand the full complement and range of genomics, genetics, and epigenetics in which we live -- and how we interact with this milieu in order to work out our lives.

Genetics and evolution have been underrated and ignored by most human intellectuals. But no one -- including these neglectful intellectuals -- is ignored by the genetic universe we inhabit. Not one living thing.

Cross-posted from Al Fin, the Next Level

Genetic Tweaks Create Super-Mice w/ Super-Charged Mitochondria

Swiss scientists have discovered that knocking out the nuclear receptor corepressor 1 (NCoR1) gene in the muscles of mice allow the animals to run farther, and faster. Knocking out the same gene in fat cells eliminated the problem of diabetes in the mice. And those are only two tissues, of the many types of tissues in a mouse's body. I wonder if knocking out the NCoR1 gene in human muscles would create a super athlete?

Knocking out a particular gene in muscle lets mice run twice as far as normal. Knocking out the same gene in fat cells allows the animals to put on weight without developing type-2 diabetes.

The discoveries could lead to new treatments for diabetes or for invigorating muscles in elderly people and in those with wasting diseases, say Johan Auwerx of the Federal Polytechnic School of Lausanne, Switzerland, and colleagues.

...Auwerx and his colleagues used a targeted virus to knock out the gene that makes a protein called nuclear receptor corepressor 1 (NCoR1) in the muscle of mice. Without NCoR1, mitochondria, which power cells, keep working at full speed. "Effectively, the mice go further, faster, on the same amount of gas," says Auwerx.

"The treated mice ran an average of 1600 metres in 2 hours, compared with 800 metres for untreated mice," he says.

...Auwerx warns athletes not to try to grow their muscles and stamina illicitly by somehow targeting the NCoR1 protein, however.

"We only know what happens if it's knocked out either in fat or muscle, and it could have serious side effects on other organs," he says. Also, he points out that without NCoR1, all fetuses perish, so it plays a vital but undiscovered role in fetal development. _NewScientist

Right. As if Auwerx' warnings would have any effect on a determined athlete's plans. And there are likely several other ways for athletes to tweak their muscles' genes, to gain an advantage.

One gene, for example, called MYH16, contributes to the development of large jaw muscles in other apes. In humans, MYH16 has been deactivated. (Puny jaws have marked our lineage for as least 2 million years.) Many people have also lost another muscle-related gene called ACTN3. People with two working versions of this gene are overrepresented among elite sprinters while those with the nonworking version are overrepresented among endurance runners. _Slate

More muscle boosting genes:

CNTF 1357 G → A polymorphism and the muscle strength response to resistance training Jnl Appl Physio 2009

Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates Sci Transl Med 2009

Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors PNAS 2008

Increased muscle PGC-1α expression protects from sarcopenia and metabolic disease during aging PNAS 2009

Genetically boosted athletes are inevitable, once stealth techniques of controlling gene expression and transfer are developed. But that also means that viable means of strengthening the muscles, bones, and other tissues that normally weaken with ageing, will also be within reach. So it's best not to complain too loudly about the athletes who tweak themselves for advantage, so long as the rest of us can win in the game of life.

Abstract from Cell:

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/δ, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function. _Cell

Cross-posted from an Al Fin Longevity posting

Programmed to be Zombies? Stealth Genetics of Brain Transformation

Once thought to be rare, these events actually take place surprisingly often. According to one recent estimate, they occur in many or most brain cells, perhaps several hundred times within each cell...Many of the insertion sites were located within genes that play key roles in normal brain function. These include genes encoding receptors for the neurotransmitter dopamine and membrane transporters that mop up neurotransmitter molecules from the spaces between neurons after their signaling is complete... Others were found in genes encoding regulatory proteins that are linked to psychiatric illnesses such as schizophrenia and the developmental disorder Smith–Magenis syndrome. _SciAm

Slow Progressive Stealth Zombie Transformation
What if the people around us are not who we think they are? What if we continue to see them as someone they once resembled, while they have been subtly changing over time to something else?

Humans are defined by their brains. We know that their brains are shaped by a host of chance events involving genes, experiences, accidents etc. But what if these brains are changing in ways we do not understand, in ways we cannot control, so that over time these persons around us have changed into something else? I am not talking about diseases of the brain, but something much more subtle.

Here is a glimpse into the genetics of stealthy brain transformation which may help explain why that person next to you is not who you think they are:

Mobile DNA molecules that jump from one location in the genome to another may contribute to neurological diseases and could have subtle influences on normal brain function and behavior, according to a study published October 30 in Nature. (Scientific American is part of Nature Publishing Group.)

Retrotransposons are mobile genetic elements that use a copy-and-paste mechanism to insert extra copies of themselves throughout the genome. First discovered in plants about 60 years ago, they are now known to make up more than 40 percent of the entire human genome and may play an important role in genome evolution.

...The researchers also found that there was far more jumping-gene activity in the hippocampus than in the caudate nucleus. This is interesting, because the hippocampus is known to be critical for learning and memory, and is widely thought to be one of the few parts of the brain that continues to produce new cells throughout life. "It is tempting to speculate that genetic differences between individual neurons could impact memory," Faulkner says, "but we have no evidence yet that this is the case."

Retrotransposons are normally silenced to prevent harmful mutations from occurring in egg and sperm cells, but are mobilized during certain stages of brain development, when neurons are being produced from dividing stem cells. Retrotransposons then take the opportunity to jump at random into parts of the chromosome that have been opened up for DNA replication.

As well as generating mutations by inserting themselves into and disrupting genes, retrotransposons can alter gene activity if inserted into adjacent regulatory regions of DNA.

...Once thought to be rare, these events actually take place surprisingly often. According to one recent estimate, they occur in many or most brain cells, perhaps several hundred times within each cell. Each neuron is likely subjected to a unique combination of insertions, leading to a genetic variability within populations of cells.

The full significance of this "genomic plasticity" is still not clear, but the authors suggest that it could influence brain development and behavior. It may, for example, partly account for the differences in brain structure and behavior between identical twins, and could even affect thought processes by subtly influencing the changes in nerve cell connections that occur with experience. _SciAm

It is becoming more and more difficult to claim that all humans are essentially the same, genetically. In fact, it is becoming more difficult to say that a person is the same today, genetically, as he was yesterday. Conventional methods of genomic sequencing do not detect many of these subtle genetic and epigenetic differences, suggesting the need for more sophisticated tools and screening methods.

One thing is certain: This changing nature of the brain -- the core of a human's self and being -- will require some rethinking of how societies should be organised. Humans with changing brains will need to be raised and taught to live in a dynamic and changing society. They must be given tools of competence, self reliance, and resilience. And they must be given the freedom to adapt to the inevitable changes which always occur.

Just the opposite of the traits one sees in the sheltered, academically lobotomised psychological neotenate -- who demands to be taken care of his entire life.

We can no longer afford this longing for dependency and stasis which defines most modern welfare state mentalities. This headlong rush for security, this raucous cry to be taken care of by an all-powerful state -- we cannot afford this delusional belief any longer. In a world of clashing cultures, this whining chorus of wankers is a suicidal lullaby. Particularly when the core populations of these affluent societies is shrinking so quickly.

Humans must learn to expect massive, dynamic changes over the course of their lives, both outside themselves and inside themselves. They must learn to be prepared to meet these changes on their own terms.

Retrotransposons and Human Genome Evolution

Abstract of Nature study:

Retrotransposons are mobile genetic elements that use a germline ‘copy-and-paste’ mechanism to spread throughout metazoan genomes1. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease2, 3. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells4, 5, excluding early embryo development and some malignancies6, 7. Recent reports of L1 expression8, 9 and copy number variation10, 11 in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes.

More: Scientists key on changes in brain gene expression over the lifetime

In the studies, published in the Oct. 27 Nature, researchers focused not on DNA — virtually every cell’s raw genetic material is identical — but on when, where and for how long each gene is turned on over the course of a person’s life. To do this, the researchers measured levels of mRNA, a molecule whose appearance marks one of the first steps in executing the orders contained in a gene, in postmortem samples of donated brains that ranged in age from weeks after conception to old age.

...To see what those genes were up to, Šestan’s study examined mRNA levels of different genes in 57 brain samples. The team divided the brain tissue up by region, so they were also able to get an idea of genes’ behavior in different parts of the brain. A parallel study, headed by Joel Kleinman of the National Institute of Mental Health in Bethesda, looked at gene behavior in 269 brain samples from a single region called the prefrontal cortex that also spanned the lifetime.

This approach allowed the researchers to get access to the brain that had previously been impossible. _Sciencenews

We also need to remember that drug use triggers changes in brain gene expression -- some of these changes can be long-term or even "permanent." This is particularly tragic in the case of fetal brain exposure to drugs such as alcohol, methamphetamine, crack cocaine, etc. in the womb. But adolescents and young adults are also quite vulnerable to changes in brain gene expression from drug use. Bonus question: What are the most effective cultures and incubators for drug use in societies? Schools, and anywhere young peers are concentrated and on their own.

Long term behavioural change following ingestion of magic mushrooms More

Brain changes from cannabis use

And there are always new party drugs coming down the pipeline which will have unknown short and long-term effects on the brain, and brain gene expression.

Some people are naturally programmed to be zombies. Other people have to work at it.

How the Green Movement Can Trigger the Great Human Dieoff

Powerful persons in the global green movement would like to see the human population of Earth reduced by at least 90%. For several decades, many of them believed that resource depletion, energy scarcity, mass starvation, or voluntary sterilisation might achieve their grand goal. But it is slowly dawning on them that if they are to slash the human population of the planet to a size that they consider manageable, they will have to be a bit more proactive.

Just in time for the great green engineered human dieoff, biological scientists have devised the perfect method of genocidal species extinction.

IN THE urban jungle of Juazeiro in Brazil, an army is being unleashed. It is an army like no other: the soldiers' mission is to copulate rather than fight. But they are harbingers of death, not love. Their children appear healthy at first but die just before they reach adulthood, struck down by the killer genes their fathers passed on to them.

These soldiers are the first of a new kind of creature - "autocidal" maniacs genetically modified to wipe out their own kind without harming other creatures....the approach should work with just about any animal - from invasive fish and frogs to rats and rabbits....it could transform the way we think about genetically engineered animals.

... the autocidal approach could not only be used to control invasive species such as cane toads, but that it is the only method that could work in many cases. "It's the only hope we have for the long-term control and eradication of these pests," he says. "Other efforts help, but in the end they are Band-Aids in the absence of a real solution."

Thresher has come up with a way to create fish that produce only male offspring. Releasing enough of these "daughterless" fish into the wild, with each passing on the daughterless habit, would turn a thriving invasive population into a bunch of reluctant bachelors destined for extinction.

...Models suggest that releasing enough daughterless carp to make up 5 per cent of the total population would effectively eradicate carp in the Murray-Darling basin by 2030. Thresher's models also suggest pests such as cane toads and rats could be tackled this way.

... One [approach] that has particular promise exploits chunks of "selfish" DNA that can spread themselves through the population and kill only when two copies are inherited. In theory a one-time release of just a few insects, rather than the continual release of millions, could wipe out a wild population (New Scientist, 22 March 2003).
_NewScientist

ArmageddonOnline.org
The last paragraph from the excerpt above describes the most subtle approach, and perhaps the easiest approach to genocide for greens to take. But they should be prepared to wait several generations to see the completion of their grand project. Such an approach should also allow environmentalists to create an antidote, so they they themselves and their associates could continue to live and procreate indefinitely. Think of it: a master race of environmentalists, sitting back and watching most of the rest of humanity fade away.

It is an approach without gas chambers, without germs, poisons, bullets, or bombs. A clean, test-tube approach that could propagate death and genocide far more broadly than any method previously devised.

Google Tech Talk: Steve Hsu -- Genetic Basis for Intelligence

This fascinating Google Tech Talk was given by Steve Hsu last week, and just put up at Google Tech Videos. Steve is a physics professor at the University of Oregon, with a special interest in human intelligence.

Slides for Steve Hsu's talk (PDF)

Hsu is involved in a study which seeks to find links between genes and high IQ. The study is looking for individuals with IQs that test higher than 3 standard deviations above the mean, in a clear effort to cut to the chase.

Hsu's talk is well worth watching for anyone interested in the genetics of cognitive ability. As high tech infrastructures grow more sophisticated and crucial to advanced societies' successes, their high IQ smart fractions take on an ever greater importance.

Smarter Near the Poles, and Nearing Clockwork Orange?

WiredHumans apparently evolved larger eyes and brains as they migrated closer to the poles. The larger eyes would allow for better adaptation to lower light levels in the wintertime. The larger brains would allow for better adaptation to the greater challenges of radically changing seasons.

Anthropologists at Oxford University collected 55 skulls, dating from the 1800s, that represented 12 different populations from around the globe. The researchers measured the eye socket and brain volumes and plotted them against the latitude of each individual’s country of origin.

The team, lead by the Institute of Cognitive and Evolutionary Anthropology’s Eiluned Pearce, found a significant positive correlation between the size of brain and the latitude of the country. People from the northern-European countries of Scandinavia had the biggest brains, while Micronesians, from just north of the equator, had the smallest. _Wired

While political correctness forces the authors to deny that the larger brains have anything to do with the demonstrated higher intelligences of peoples who migrated farther from the equator, such higher intelligence has been shown to correlate with higher latitude as well as brain size, time after time. HBD (human biodiversity) deniers argue this point out of ignorance, but with the coming of advanced brain imaging techniques which can determine the comparative sizes of some of the very smallest brain nuclei, such denial is becoming infantile at best.

Meanwhile, Cal Tech researchers are homing in on a part of the brain which controls human aggression and violence. We may well be approaching a "Clockwork Orange" scenario, where violence-prone people will be conditioned or modified to remove their violent tendencies.

Our story starts in the hypothalamus, an ancient region of the brain, conserved throughout mammalian evolution. In humans, it is about the size of an almond, housing a motley collection of neurons. These cells regulate distinct bodily functions such as temperature, circadian rhythms, sleep, hunger, thirst, sex, anger, aggression and response to stress. Earlier work showed that electrical stimulation of some of these sites provokes cats and rats to sudden bouts of rage and that the ventromedial hypothalamus (VMH) has some involvement in sexual behaviors. Yet the precise location of attack-promoting neurons, their mode of action, and the interplay between aggression and mating—normally two opposing forms of social interactions—had remained deeply mysterious.

Enter a team from the California Institute of Technology, under the leadership of neurobiologist David J. Anderson. In four steps, the seven scientists, spearheaded by postdoctoral fellow Dayu Lin (now at New York University), nailed down the critical role of aggression neurons in the VMH. The setting was the home cage of an individually housed, sexually experienced male mouse. When another mouse, either a male or a sexually receptive female, entered the cage, the resident male mouse usually attacked the former but mated with the latter. The scientists video recorded the behavior so that the detailed time course of interaction of every pair of animals—the cautious sniffing and retreating, the pushing, shoving and biting, the mounting and consummatory activities—in hundreds of encounters could be statistically analyzed and time-aligned using software developed by machine vision engineers Piotr Dollar and Pietro Perona.

...Stimulating the VMHvl [Editor: The VMHvl is the ventrolateral portion of the ventromedial hypothalamus] when the mouse was by itself did not do anything. Yet in the presence of another animal, the mouse initiated a concerted attack, often by biting the back of the intruder. Unusually for this species, the illuminated male indiscriminately attacked female, castrated male or anesthetized mice—and sometimes even a blown-up latex glove. Aggression ceased once the light stopped. The infection and light delivery had to be targeted to the VMHvl nucleus; stimulating nearby regions did not produce such an effect. It is a striking and immediate demonstration of the link between neurons and behavior. Exciting VMHvl neurons causes aggression.

Finally, Anderson and his team turned to the question of whether the VMHvl cells are necessary for aggression to occur. Using a different technique, they genetically “silenced” VMHvl cells, turning them effectively off for days at a time. This silencing significantly reduced the chances of an aggressive encounter and lengthened the time it took to initiate an attack. _SciAm

The researchers were able to temporarily "dim down" the tendency for the mouse to resort to violence. The techniques for achieving this level of control over the mouse VMHvl nucleus are quite tedious. Eventually the same level of control will be achieved with a nasal spray containing nano-scale capsules of precisely targeted gene modifiers.

Violence is endemic to large parts of Asia, South America, and Africa. And even within the troubled multicultural urban areas of Europe, Oceania, and North America, deadly violence can be a daily phenomenon. Will human authorities utilise the coming tools of behaviour modification, even if they interfere with "free will?" Or is it better to pack prisoners in cages like mammalian sardines, and allow them to do with each other as they wish? The intersection of sophisticated brain and genetic research with widespread sociopathology is likely to prove interesting.

Human Intelligence Comes from the Genes

LAMC3 Gene and Effect on Brain Convolutions
The difference between the brain on the left above and the brain on the right, comes from a single gene -- LAMC3 -- which influences the formation of convolutions in the cerebral cortex. Brain convolutions allow for much greater volume of cerebral cortex, which is associated with the higher intelligence seen in apes, cetaceans, and humans (one of the apes). An alteration of the nucleic acid sequence in the LAMC3 gene in humans can apparently lead to the loss of convolutions in the cortex in affected individuals, as seen in the image above.

The folding of the brain is seen only in mammals with larger brains, such as dolphins and apes, and is most pronounced in humans. These fissures expand the surface area of the cerebral cortex and allow for complex thought and reasoning without taking up more space in the skull. Such foldings aren't seen in mammals such as rodents or other animals. Despite the importance of these foldings, no one has been able to explain how the brain manages to create them. The LAMC3 gene – involved in cell adhesion that plays a key role in embryonic development – may be crucial to the process.

An analysis of the gene shows that it is expressed during the embryonic period that is vital to the formation of dendrites, which form synapses or connections between brain cells. "Although the same gene is present in lower organisms with smooth brains such as mice, somehow over time, it has evolved to gain novel functions that are fundamental for human occipital cortex formation and its mutation leads to the loss of surface convolutions, a hallmark of the human brain," Gunel said. _Medicalxpress

Thousands of genes take part in the intricate developmental dance of forming the central nervous system in all its complexity. But specific genes play more dominant roles in differentiating human brains from brains of "lower" animals.

Genes control the size of particular systems and components of the brain which are instrumental in providing for more rapid mental processing and more complex processing. Some brains can hold more ideas in the mind simultaneously, while performing transformative operations on those ideas. "Human calculators" capable of computing solutions to complex arithmetical and mathematical problems in their heads, are one obvious example. But the mental machinations of scientific theorists, elite diagnosticians, and top level novelists, illustrate the same type of differentiation of mental ability -- largely originating at the genetic level.

James Watson -- one of the discoverers of the modern genetic theory of DNA inheritance -- received almost universal condemnation for expressing a few elementary facts of human genetic biodiversity. Here is some background information concerning that shameful episode of modern human culture and its prejudices:

GNXP: James Watson tells the Inconvenient Truth

Slate: Created Equal [AF Note: After being threatened with a similar fate as that of Watson, the much beaten-down Saletan (author of the slate piece above) published a "mea culpa" and submitted to the PC inquisition]

Useful PDF article from Robert Plomin discussing Genes and Intelligence

It is critical to understand how many genes are involved in weaving the fabric of higher intelligence. It is not a question of finding THE GENE for intelligence. Rather it is a question of understanding how all the many genes which create the potential for intelligence, work together.

And it is important to become a bit more sophisticated about how a crucial variability in gene expression can occur -- even when conventional genetic analyses fail to distinguish between two genomes.

Humans are not all the same. In fact, no two humans are exactly the same -- even identical twins. This is true for reasons of gene expression, in all its many levels of complexity -- both known and unknown. These differences can also originate from differences in experience and culture, as in when identical twins are separated at birth and raised in entirely different environments. But even then, the powerful impact of genes on the life outcome of the separated twins is all to obvious.

IQ is not everything. Executive Function (EF) is also crucial to life success. But EF is perhaps even more heritable than IQ. That is why it is so crucial to take advantage of a child's critical developmental windows for boosting the components of competent thinking, acting, and planning when one can. After that time period passes, it is mostly too late for those at the greatest genetic disadvantage.

Is Mental Illness Preventable?

Of the 10 leading causes of disability in the world in 1990, five were mental disorders; specifically unipolar depression, alcohol use, manic depression, schizophrenia and obsessive-compulsive disorder (Murray and Lopez, 1996). It is clear that both the extent of mental health problems and the enormous associated personal, social and financial cost can not be addressed by treatment services alone. _Robinson et Pennebaker

Schizophrenia.com
Schizophrenia is one of the most debilitating and disabling of the mental illnesses. So if we could find a way to prevent schizophrenia -- even a substantial proportion of the disease -- we would be making impressive progress toward the goal of preventing mental illness.

Recent research findings from Duke and Johns Hopkins suggest that a proportion of schizophrenia with genetic causes could be prevented by early detection of susceptible persons in early childhood, with appropriate intervention before symptoms manifest themselves in late adolescence or early adulthood. Scientists have known for decades that brain structure in schizophrenia was not normal -- and even pointed toward an early developmental "lesion" as the cause of the structural abnormalities.

The critical network of signals which control early brain development is becoming better understood -- both in terms of general development and in terms of specific brain diseases when the signaling network goes awry. Here is more about the recent Duke et Johns Hopkins research:

Katsanis, who directs the Duke Center for Human Disease Modeling, and Akira Sawa, M.D., Ph.D., a Professor in the Department of Psychiatry at Johns Hopkins, were introduced to each other by a clinical colleague who thought that Bardet-Biedl syndrome (BBS) proteins that are involved in transport duties within cells might have a role in schizophrenia. Katsanis is an expert in using BBS genetic mutations and proteins to learn more about other diseases. BBS is a complex genetic disease with autism-like symptoms, cognitive defects and depression. Sawa is an expert on DISC1, the protein named Disrupted in Schizophrenia 1, known to be a major susceptibility factor for schizophrenia and related disorders.

Together, they discovered that these proteins are involved in a key switch for neurons that is necessary for brain development. When DISC1 gains a phosphate group at a specific site, it recruits BBS1. When BBS1 is missing in this system, the team could observe defective neuron migration, while a model with no DISC1 at all leads to defects in both cell proliferation and migration.

...Katsanis predicts that, for perhaps 10 percent of psychiatric illness, the illness is primarily driven by defects in this switch system. "So we now have ways to interpret variation in humans, in a context that is relevant to their particular cases, to their physiology -- that is where medicine will move next," Katsanis said.

...The study was published by Nature journal on April 6 in its advance online publication. _SD

The researchers were looking at brain signaling which controls early brain development -- the multiplying of brain neurons and subsequent placement in proper locations, orientiation, and connectivity to other parts of the brain. But there is another "brain growth spurt" which occurs just before adolescence, which could be just as critical to the subsequent development of schizophrenia and other types of mental illness which first manifest in adolescence or early adulthood. This neuronal growth spurt is no doubt also under the control of brain signaling proteins.

Prevention comes into the picture when scientists learn to correct abnormal signaling in early stages of development, or to compensate for abnormal brain development, later in childhood. Some genetic abnormalities can be treated now, and the opportunities to treat more genetic problems are growing rapidly.

That means that besides mental illness, many disadvantages which are widespread in the third world and in disadvantaged ethnic groups -- and which are at least partially genetically mediated (such as low intelligence and poor executive function) -- should be amenable to treatment in the not so distant future.

It is the denial of such genetically mediated disadvantages and disabilities which dooms sufferers to lifetimes of misery and underachievement. Such HBD deniers likewise doom entire societies and regions to generations of misery, poverty, widespread disease, and hopelessness.

Poor, Bare, Forked Animals Begin to Decipher Epigenome

NIH
The epigenome is the system of genome modifiers that guide gene expression. Epigenetics determines whether a cell will be a brain cell or a liver cell, even though both cells possess the same genome. Some preliminary results are beginning to come in from the US NIH's modENCODE program.

Sarah C.R. Elgin, PhD, the Viktor Hamburger Distinguished Professor in Arts & Sciences, who led the Washington University lab that is part of one of the modENCODE teams offers an explanation.

“We learned many things from the Human Genome Project,” Elgin says, “but of course it didn’t answer every question we had!

“Including one of the oldest: We all start life as a single cell. That cell divides into many cells, each of which carries the same DNA. So why are we poor, bare, forked creatures, as Shakespeare [Al Fin: Lear ActIII SceneIV] put it, instead of ever-expanding balls of identical cells?

“This work,” says Elgin, “will help us learn the answer to this question and to many others. It will help us to put meat on the bones of the DNA sequences.” _WUNewsroom

Wikipedia

The epigenetic code that determines whether genes are silenced or expressed consists of chemical modifications to the DNA, to “tails” that hang off the histones, or other packaging proteins.

“ENCODE and modENCODE are much more complicated projects than the Human Genome Project,” Elgin says, “because the DNA sequence is pretty much the same in every cell type, whereas the chromatin structure is different in every cell type. In fact we believe it is the chromatin structure that differentiates one cell type from another.

“That means we can’t just do one genome for the organism. We have to do every different cell type to get a complete picture of the organism, and that’s a daunting prospect.” _WU

The research relies upon the most advanced bio-research and computing technologies. The amount of data generated is staggering, and far beyond what an unaided human could organise and comprehend.

But this is the beginning of the true meat of genetics. Sure, they are looking at worms and fruit flies now. But humans and all human symbionts and parasites are on the list to be comprehensively studied. The knowledge to be gained will provide unimaginable benefits.

What Is Metabolic Engineering and Why Should We Care?

LBLNewsMetabolic Engineering is one of those bastard terms which is often spawned by science-savvy folks in academia who are functionally illiterate. For example, MIT has a lab department of Bioinformatics and Metabolic Engineering. Rice has studies in Biological Chemistry and Metabolic Engineering. Harvard teaches Systems Metabolic Engineering. Cornell has a lab for Biomolecular and Metabolic Engineering. At Berkeley, the subject falls under the Department of Chemical and Biomolecular Engineering... and so on. When will we be given entire departments of Respiratory Engineering, Mitochondrial Engineering, Liposome Engineering, or Cholesterol Membrane Engineering? There truly is no end to the number of departmental classifications that could be spawned by the postmodern twits of academia who have acquired a little bit of specialised scientific training.

Forgive me, I got a bit sidetracked. Chemical engineer Jay Keasling has published an article in Science discussing the "Future of Metabolic Engineering," in which he looks at the possibilities of creating designer molecules, cells, and micro-organisms.

In a paper published in the journal Science titled “Manufacturing molecules through metabolic engineering,” Keasling discusses the potential of metabolic engineering – one of the principal techniques of modern biotechnology – for the microbial production of many of the chemicals that are currently derived from non-renewable resources or limited natural resources. Examples include, among a great many other possibilities, the replacement of gasoline and other transportation fuels with clean, green and renewable biofuels.

“Continued development of the tools of metabolic engineering will be necessary to expand the range of products that can be produced using biological systems, Keasling says. “However, when more of these tools are available, metabolic engineering should be just as powerful as synthetic organic chemistry, and together the two disciplines can greatly expand the number of chemical products available from renewable resources.”

...Metabolic engineering is the practice of altering genes and metabolic pathways within a cell or microorganism to increase its production of a specific substance. Keasling led one of the most successful efforts to date in the application of metabolic engineering, when he combined it with synthetic organic chemistry techniques to develop a microbial-based means of producing artemisinin, the most potent of all anti-malaria drugs. He and his research group at JBEI are now applying that same combination to the synthesis of liquid transportation fuels from lignocellulosic biomass. In all cases, the goal is to engineer microbes to perform as much of the chemistry required to produce a desired final product as possible.

“To date, microbial production of natural chemical products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered,” Keasling says. “Production of non-natural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism, and by engineering enzymes to have new function.”

These efforts have utilized well-known, industrial microorganisms, but future efforts, he says, may include designer molecules and cells that are tailor-made for the desired chemical and production process. _LBLNews_via_BrianWang

Sound familiar, this metabolic engineering? Like a contrived illegitimate offspring of genetic engineering, synthetic biology, and metabolomics? It's bad enough to have a proliferation of -omics, such as genomics, proteinomics, metabolomics, glycomics, lipomics . . . It is almost enough to turn a person homicidalomic.

Psychiatry with its DSM is almost as insane. But these irrational and cumbersome systems of classification tend to evolve by the method of poorly punctuated disequilibrium, leaving those downstream to deal with the offalness of it all.

Does Keasling simply want to excel in a field that another researcher -- Craig Venter -- has already staked out -- synthetic biology? Venter has long since founded a company called Synthetic Genomics. Is it possible that Keasling is unwilling to share the same field with a person such as Venter, who is already hot on the trail of the very things that Keasling claims to be pursuing in the name of Metabolic Engineering? Fine. Do the same thing, but call it something different. No one will ever know.

Greater Human Genetic Diversity Than Previously Believed

ImgSource

As humans look more deeply into their genetic and epigenetic complement, they are discovering far greater genomic differences between humans than previously believed possible. The 1000 Genomes Project is reporting on results from its pilot phase:

Evan E. Eichler and coworkers of the University of Washington, Seattle, used data from the 1000 Genomes Project to analyze copy-number variations, which are differences in the number of times a particular gene sequence appears in the genome (Science 2010, 330, 641). About 1,000 genes "have been largely inaccessible to traditional genetic study as a result of their repetitive nature," Eichler said at the press briefing. Using newly developed sequence analysis algorithms and sequence tags, his team investigated copy-number variations in these genes, he said.

Eichler's team found that copy-number variations occur in fewer than 10% of human genes. Many of these genes map to regions that had been previously identified as highly repetitive and have been implicated in diseases such as schizophrenia and autism, the authors note.

Even at the pilot stage, the 1000 Genomes Project has already provided "a more complete catalog" of human genetic variation than was available previously, Durbin said. The project is already moving forward with its main phase, with the goal of sequencing 2,500 genomes. _ACSPubs

Whether 1000 genomes or 2500 genomes, the study is still quite preliminary, in terms of understanding the astounding magnitude of variation within the broad human genome and epigenome. As we begin to comprehend the vast numbers of differences in gene expression between even the closest of relatives, we may get a glimmer of understanding of how our molecular makeup generates the diverse worlds we inhabit.

Abstract of paper:

Copy number variants affect both disease and normal phenotypic variation, but those lying within heavily duplicated, highly identical sequence have been difficult to assay. By analyzing short-read mapping depth for 159 human genomes, we demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kilobase pairs, ranging from 0 to 48 copies. We identified 4.1 million "singly unique nucleotide" positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identify human-specific expansions in genes associated with brain development, reveal extensive population genetic diversity, and detect signatures consistent with gene conversion in the human species. Our approach makes ~1000 genes accessible to genetic studies of disease association.

Goat-Smelling Desert Dwellers Confused by Brasilian Interference

ImageSource

For many years, the All-Peninsular Goat-Smelling Mooch Award has been won by either Ahmed or Abdul. (It should be noted that the word "mooch" means something different in Arabic, being more linguistically akin to the Yiddish word "mensch".) Al Fin traveled to the peninsula to interview Abdul and Ahmed, the most highly skilled goat-smellers in peninsular history, to question them about Brasil's latest interference in the goat genome, and the implications this may have for their profession in the future.

Al Fin: Thank you very much, Abdul and Ahmed, for meeting with me today.

Ahmed and Abdul in unison: Salaam aleikum, Al.

AF: Wa aleikum salaam. I'll start with Abdul first. What do you think about Brasil's interference with goat genetics?

Abdul: It is a serious problem, Al. These interfered goats do not smell the same as a natural goat. It gives me a headache to think what these cursed Brasilian scientists are doing.

AF: I understand that some goat-smellers are worried that the Brasilians will insert some pig genes into their goats, and then release the pig-goats into peninsular herds to inter-breed with natural goats. Ahmed, what have you heard in that regard?

Ahmed: I was enraged when the imam announced this outrage at Friday noon prayer. We rushed into the streets with hands full of stones, looking for infidels and perverts. Fortunately we found a woman walking without a veil, with her head uncovered. It would have been a shame to waste the stones.

AF: I see. But can't you tell the difference in smell between natural goats and Brasil-interfered goats? Wouldn't such a thing lead to greater demand for goat-smellers, and higher profits for you?

Abdul: No, Al, you don't understand. Just to smell such a pig-goat would contaminate a goat smeller so that he could not go to mosque without enduring a prolonged purification ritual over a period of many days. Many of our best clients would be reluctant to hire us with such a taint over our heads.

AF: Hmmm. What do you intend to do, then?

Ahmed: We must declare jihad against the Brasilian scientists and destroy their laboratories before they can achieve their blasphemous goals.

AF: But what about all the good things that could come from the transgenic goat programs? Destroying the laboratories may prevent some important medical breakthroughs.

Abdul: Not our problem, Al. We must do what we must do.

AF: So. Thanks for meeting with me today Abdul and Ahmed.

A&A: As Salaamu Aleikum, Al.

Technology Review article about transgenic goat experiments in Brazil

Genes and IQ: The Connection is Real, But Complex

Robert Plomin, at King's College London, is reporting on a study of 4,000 British children which suggests that over 200 genes are responsible for superior reasoning ability and IQ. More:

SCIENTISTS have identified more than 200 genes potentially associated with academic performance in schoolchildren.

Those schoolchildren possessing the "right" combinations achieved significantly better results in numeracy, literacy and science.

The finding emerged from a study of more than 4000 British children to pinpoint the genes and genetic combinations that influence reasoning skills and general intelligence.

One of its main conclusions is that intelligence is controlled by a network of thousands of genes with each making just a small contribution to overall intelligence, rather than the handful of powerful genes that scientists once predicted.

The researchers believe their work could eventually lead to genetic tests to predict babies' academic potential.

"This kind of research could help us develop genetic tests to predict which kids are at risk of developing problems with their schooling, so that we could intervene to help them," said Robert Plomin, professor of behavioural genetics at the Institute of Psychiatry at King's College London, who will describe his work today at a meeting of the Royal Society.

_Australian

Scientists have known for years how important gene patterns are to the development of the brain. Specific gene variants can have a crucial effect on the wiring of the brain, and on the speed and efficiency of brain functioning. Individual genes have been identified, which are felt to have an influence on human intelligence, but it is the larger pattern of gene combinations which must be studied and understood.

Human intelligence and cognition are too complex to rely on any one gene. But the computational methods to make sense out of the massive interplay of the hundreds of genes which may affect intelligence have not always been available, or trustworthy.

But slowly, as scientists learn to study the interactions of hundreds of genes, the relationship between human intelligence and gene variants can become more clear. It is an important area of study. Only by thoroughly understanding how our genes make us what we are -- in partnership with our environment -- can we find the best ways to grow into the sort of humans who can boldly step into the hazardous future, and go where things are really scary. But in a good way.

Human DNA to Geneticists: "You Don't Know Me"

“Our new technology quickly analyzes huge DNA molecules one at a time, which eliminates the copy machine step, reduces the number of DNA jig-saw pieces and increases the unique qualities of each piece,” Schwartz says. “These advantages allow us to discover novel genetic patterns that are otherwise invisible.” _Newswise

Human geneticists are learning a hard lesson in science: what you still don't know will almost always dwarf what you have learned. Human DNA is far more variable than geneticists have realised. Which means that science journalists and the general public are completely in the dark on the vast magnitude of human genetic variability.

Genetic abnormalities are most often discussed in terms of differences so miniscule they are actually called "snips" -- changes in a single unit along the 3 billion that make up the entire string of human DNA.

...“There’s a whole world beyond SNPs — single nucleotide polymorphisms — and we’ve stepped into that world,” says Brian Teague, a doctoral student in genetics at the University of Wisconsin-Madison. “There are much bigger changes in there.”

Variation on the order of thousands to hundreds of thousands of DNA’s smallest pieces — large swaths varying in length or location or even showing up in reverse order — appeared 4,205 times in a comparison of DNA from just four people, according to a study published May 31 in the Proceedings of the National Academy of Sciences.

Those structural differences popped into clear view through computer analysis of more than 500 linear feet of DNA molecules analyzed by the powerful genome mapping system developed over nearly two decades by David C. Schwartz, professor of chemistry and genetics at UW-Madison.

“We probably have the most comprehensive view of the human genome ever,” Schwartz says. “And the variation we’re seeing in the human genome is something we’ve known was there and important for many years, but we haven’t been able to fully study it.”Newswise_via _SD

This means that as the technology of DNA analysis improves, more and more of the variability of human behaviour and development is likely to be attributed to genetic and epigenetic variability. Environment will continue to be important, since environment can strongly influence gene expression, among other important variables.

But the vast variability of the human genome is becoming more obvious to even the most stubborn denier of HBD (human biological diversity). The best approach for these "deniers of the genes" would be to now focus on how to best use the environment to influence gene expression for optimal development and health.