This epigentics book looks interesting. I'll order a copy today.
The Epigenetics Revolution: How Modern Biology Is Rewriting Our Understanding of Genetics, Disease, and Inheritance by Nessa Carey
Epigenetics can potentially revolutionize our understanding of the structure and behavior of biological life on Earth. It explains why mapping an organism's genetic code is not enough to determine how it develops or acts and shows how nurture combines with nature to engineer biological diversity. Surveying the twenty-year history of the field while also highlighting its latest findings and innovations, this volume provides a readily understandable introduction to the foundations of epigenetics.
Nessa Carey, a leading epigenetics researcher, connects the field's arguments to such diverse phenomena as how ants and queen bees control their colonies; why tortoiseshell cats are always female; why some plants need cold weather before they can flower; and how our bodies age and develop disease. Reaching beyond biology, epigenetics now informs work on drug addiction, the long-term effects of famine, and the physical and psychological consequences of childhood trauma. Carey concludes with a discussion of the future directions for this research and its ability to improve human health and well-being.
Biography Here's the official version... Nessa Carey has a virology PhD from the University of Edinburgh and is a former Senior Lecturer in Molecular Biology at Imperial College, London. She has worked in the biotech and pharmaceutical industry for ten years. She lives in Bedfordshire and this is her first book. And what else? After leaving school I went to the University of Edinburgh to become a vet. This didn't last because I was allergic to fur, unable to think in 3D (not good for anatomy), quite bored and really rubbish at the course. So I dropped out and at Catford Job Centre, in amongst the ads for short order chefs (I couldn't cook) and van drivers (I couldn't drive), was one for a forensic scientist. And oddly enough I had always wanted to work at this end of crime - I must have been the only kid in the UK who had read a biography of Bernard Spilsbury by the age of 11. So for five years I worked at the Metropolitan Police Forensic Science Lab in London and studied part-time. I then realised that I loved academic science and went off to do a PhD. At the University of Edinburgh. In the veterinary faculty. After that, it was the academic route of post-doc, Lecturer and Senior Lecturer. But I had a tendency to wander off on routes that intrigued me - degree in Immunology, PhD in Virology, post-doc in Human Genetics, academic position in Molecular Biology. Such wandering isn't necessarily the best idea in academia but the breadth of experience is really valued in industry. I've spent 10 years in biotech and have recently moved to the pharmaceutical sector. And outside of work? I love birdwatching (no, I don't have a life-list), cycling, scavenging stuff from skips, and growing vegetables. I have a fantasy about one day having a smallholding (where I will starve to death if I really have to be self-sufficient) and I can't wait to write my next book. And I can now cook. And drive.
UW genome scientist Dr. John A. Stamatoyannopolous led several major Project ENCODE related studies.
The ENCODE project has looked deeper into "junk DNA" than ever before. And junk it is not: According to more than 30 research papers published today (Sept. 5) in a number of journals including Science and Nature, at least 80 percent of the genome is biologically active, with much non-protein-coding DNA regulating nearby genes in a complex dance of influence. [Mysteries of Human Evolution]
The findings reveal that the genetic basis of many diseases may not be in protein-coding genes at all, but in their regulatory neighbors. For example, genetic variants related to metabolic diseases pop up in genetic regions that activated only in liver cells. Likewise, regions activated in immune cells hold variants that have been associated with autoimmune disorders such as lupus.
"These breakthrough studies provide the first extensive maps of the DNA switches that control human genes," study researcher John Stamatoyannopoulos, associate professor of genome sciences and medicine at the University of Washington, said in a statement. "This information is vital to understanding how the body makes different kinds of cells, and how normal gene circuitry gets rewired in disease. We are now able to read the living human genome at an unprecedented level of detail, and to begin to make sense of the complex instruction set that ultimately influences a wide range of human biology."
Well, once again, one man's junk is another man's treasure!
New DNA project shows us living beyond our genes
by Robert Bazell and Maggie Fox, NBC News In what many scientists say is a revolution in biology, a giant new project is rewriting our understanding not only of what causes diseases or what makes our eyes a certain color, but what makes us human. And it turns out scientists have been looking in the wrong place for a very long time.
The bounty of new discoveries, released in a batch of 40 research papers on Wednesday, shows the stretches of DNA that we call genes are only a very small piece of what makes the body work. Much more important is the stuff in between the genes – stuff once dismissed as “junk DNA”. It turns out that junk DNA is what is in control, they report in the series of papers in the journals Nature,Science and elsewhere.
“This has opened up whole new galaxies. It’s like having a bigger telescope,” says Dr. Bruce Stillman, president of Cold Spring Harbor Laboratory, which played a major role in the work.
Scientists already knew in 2003, as they finished the giant Human Genome Project, that they did not have the understanding they had hoped for. It turned out that humans had just a measly 22,000 genes – fewer than some animals and far fewer even than a plant such as rice. How could something as complex and advanced as a human be boiled down into something so simple?
“We understood precious little about the processes that turns genes on and off. In short we had more questions than answers about how the human genome works,” said Dr. Eric Green, director of the National Human Genome Research Institute, which conducted the study.
The next phase of work, called ENCODE for Encyclopedia of DNA Elements, shows there’s nothing simple about it. As many as 40 million different switches are controlling these genes, turning them on and off in complex and subtle ways.
“The genome is loaded with gene controlling switches. There are literally millions of these,” Dr. John Stamatoyannopoulos of the University of Washington, who worked on the studies, told reporters in a telephone briefing.
Dr. Francis Collins, director of the National Institutes of Health, calls the findings “awesome and elegant.”
“This is the first truly comprehensive view, of how the three billion letter instruction book for human biology actually carries out its work, across many tissues and over the course of development,” he told NBC News in an interview.
Stanford University genomic expert Michael Snyder says it looks like gene mutations -- the changes in DNA sequences that we associate with causing diseases -- may only affect rare diseases. Common diseases, like heart disease, cancer, and allergy, are probably controlled elsewhere. “We think that most of the changes that affect disease don’t lie in the genes themselves, but the switches,” Snyder says.
So treating these common diseases may lie in trying to affect the switches. “The pharmaceutical industry has largely given up on genomics and the genome in favor of older approaches,” said Stamatoyannopoulos. These new findings may reinvigorate new drug research, he said. “Now we have a huge amount of genetic data about human disease that we can actually put to work to find the right kind of genes and proteins to target,” he said.
This new data will also help doctors diagnose disease in the first place, predict which treatments will work best for patients, and monitor their progress. It points the way to studies to determine the causes of hundreds of diseases including all kinds of cancer, Alzheimer’s disease, schizophrenia, heart disease, type 1 and type 2 diabetes, lupus, rheumatoid arthritis and asthma.
It also may lead to a better understanding of how our genetics determine such non-disease factors as height, weight and expected life span.
Not only that – it can help explain why humans and chimpanzeesshare 98 percent or more of our genes, yet are so different.
"Genes occupy only a tiny fraction of the genome, and most efforts to map the genetic causes of disease were frustrated by signals that pointed away from genes. Now we know that these efforts were not in vain, and that the signals were in fact pointing to the genome's 'operating system' -- the instructions for which are hidden in millions of locations around the genome," said Stamatoyannopoulos. "The findings provide a new lens through which to view the role of genetics and genome function in disease."
Another surprising finding was that the regulatory circuitry blueprints could be used to pinpoint cell types that play a role in specific diseases -- without requiring any prior knowledge about how the disease worked. For example, DNA changes associated with Crohn's disease (a common type of inflammatory bowel disease) are concentrated in the switches controlling two types of immune cells.
Researchers can use this same method to identify cell types not previously known to play a role in a particular disease, expanding our understanding of the disease process and potentially leading to new therapies.
"We now have a parts list of what makes us human," says Mark Gerstein of Yale university, who worked on the project. "What we are doing is figuring out the wiring diagram of how it all works."
The findings rewrite biology 101 for most of us. Each gene, we were taught, provided the code for a single protein. The proteins were the building blocks of cells, and the products made by the cells, from compounds called growth factors to signal-carrying chemicals. An intermediary genetic structure called RNA carried this information. ENCODE shows this is not quite so straightforward, that RNA generates the 40 million switches that can affect how and when many things happen within the cells.
“This is another grand chapter in the ongoing and historic research story that is unraveling the details about how life works, and how disease occurs,” Collins said.
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein codinggenes such as rRNA genes or tRNA genes, the product is a functional RNA. The process of gene expression is used by all known life -- eukaryotes (including multicellular organisms), prokaryotes (bacteria and archaea) and viruses - to generate the macromolecular machinery for life.
Gene structure and gene expression in higher organisms
Several steps in the gene expression process may be modulated, including the transcription, RNA splicing, translation, and post-translational modification of a protein. Gene regulation gives the cell control over structure and function, and is the basis for cellular differentiation, morphogenesis and the versatility and adaptability of any organism. Gene regulation may also serve as a substrate for evolutionary change, since control of the timing, location, and amount of gene expression can have a profound effect on the functions (actions) of the gene in a cell or in a multicellular organism.
In genetics gene expression is the most fundamental level at which genotype gives rise to the phenotype. The genetic code is "interpreted" by gene expression, and the properties of the expression products give rise to the organism's phenotype.
This replica of a tiny finger bone from Denisova Cave yielded an entire genome. Photo: Max Planck Institute for Evolutionary Anthropology.
by Adrian Cho, ScienceNOW
In a stunning technical feat, an international team of scientists has sequenced the genome of an archaic Siberian girl 31 times over, using a new method that amplifies single strands of DNA. The sequencing is so complete that researchers have as sharp a picture of this ancient genome as they would of a living person’s, revealing, for example that the girl had brown eyes, hair, and skin. “No one thought we would have an archaic human genome of such quality,” says Matthias Meyer, a postdoc at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. “Everyone was shocked by the counts. That includes me.”
That precision allows the team to compare the nuclear genome of this girl, who lived in Siberia’s Denisova Cave more than 50,000 years ago, directly to the genomes of living people, producing a “near-complete” catalog of the small number of genetic changes that make us different from the Denisovans, who were close relatives of Neandertals. “This is the genetic recipe for being a modern human,” says team leader Svante Pääbo, a paleogeneticist at the institute.
Ironically, this high-resolution genome means that the Denisovans, who are represented in the fossil record by only one tiny finger bone and two teeth, are much better known genetically than any other ancient human—including Neandertals, of which there are hundreds of specimens. The team confirms that the Denisovans interbred with the ancestors of some living humans and found that Denisovans had little genetic diversity, suggesting that their small population waned further as populations of modern humans expanded. “Meyer and the consortium have set up the field of ancient DNA to be revolutionized—again,” says Beth Shapiro, an evolutionary biologist at the University of California, Santa Cruz, who was not part of the team. Evolutionary geneticist Sarah Tishkoff of the University of Pennsylvania agrees: “It’s really going to move the field forward.”
Pääbo’s group first gave the field a jolt in May 2010 by reporting a low-coverage sequence (1.3 copies on average) of the composite nuclear genome from three Neandertals. They found that 1% to 4% of the DNA of Europeans and Asians, but not of Africans, was shared with Neandertals and concluded that modern humans interbred with Neandertals at low levels.
Just 7 months later, the same group published 1.9 copies on average of a nuclear genome from a girl’s pinky finger bone from Denisova Cave. They found she was neither a Neandertal nor a modern human—although bones of both species had been found in the cave—but a new lineage that they called Denisovan. The team found “Denisovan DNA” in some island Southeast Asians and concluded that their ancestors also interbred with the ancestors of Denisovans, probably in Asia.
But these genomes were too low quality to produce a reliable catalog of differences. Part of the problem was that ancient DNA is fragmentary, and most of it breaks down into single strands after it is extracted from bone.
Meyer’s breakthrough came in developing a method to start the sequencing process with single strands of DNA instead of double strands, as is usually done. By binding special molecules to the ends of a single strand, the ancient DNA was held in place while enzymes copied its sequence. The result was a sixfold to 22-fold increase in the amount of Denisovan DNA sequenced from a meager 10-milligram sample from the girl’s finger. The team was able to cover 99.9% of the mappable nucleotide positions in the genome at least once, and more than 92% of the sites at least 20 times, which is considered a benchmark for identifying sites reliably. About half of the 31 copies came from the girl’s mother and half from her father, producing a genome “of equivalent quality to a recent human genome,” says paleoanthropologist John Hawks of the University of Wisconsin, Madison, who was not part of the team.
Now, the view of the ancient genome is so clear that Meyer and his colleagues were able to detect for the first time that Denisovans, like modern humans, had 23 pairs of chromosomes, rather than 24 pairs, as in chimpanzees. By aligning the Denisovan genome with that of the reference human genome and counting mutations, the team calculated that the Denisovan and modern human populations finally split between 170,000 and 700,000 years ago.
The researchers also estimated ancient Denisovan population sizes by using methods to estimate the age of various gene lineages and the amount of difference between the chromosomes the girl inherited from her mother and father. They found that Denisovan genetic diversity, already low, shrank even more 400,000 years ago, reflecting small populations at that time. By contrast, our ancestors’ population apparently doubled before their exodus from Africa. The team also counted the differences between Denisovans and chimps, and found that they have fewer differences than do modern people and chimps. The girl’s lineage had less time to accumulate mutations, and the “missing evolution” suggests she died about 80,000 years ago, although the date is tentative, says co-author David Reich, a population geneticist at Harvard University. If this date—the first proof that a fossil can be directly dated from its genome—holds up, it is considerably older than the very rough dates of 30,000 to more than 50,000 years for the layer of sediment where the fossils of Denisovans, Neandertals, and modern humans all were found.
The team says the new genome confirms their previous findings, showing that about 3% of the genomes of living people in Papua New Guinea come from Denisovans, while the Han and Dai on mainland China have only a trace of Denisovan DNA. Furthermore, the team determined that Papuans have more Denisovan DNA on their autosomes, inherited equally often from both parents, than on their X chromosomes, inherited twice as often from the mother. This curious pattern suggests several possible scenarios, including that male Denisovans interbred with female modern humans, or that these unions were genetically incompatible, with natural selection weeding out some of the X chromosomes, Reich says.
The new genome also suggests one odd result. By using the detailed Denisovan genome to sharpen the view of their close cousins the Neandertals, the team concludes that living East Asians have more Neandertal DNA than Europeans have. But most Neandertal fossils are from Europe; paleoanthropologist Richard Klein of Stanford University in Palo Alto, California, calls the result “peculiar.”
Most exciting to Pääbo is the “nearly complete catalog” of differences in genes between the groups. This includes 111,812 single nucleotides that changed in modern humans in the past 100,000 years or so. Of those, eight were in genes associated with the wiring of the nervous system, including those involved in the growth of axons and dendrites and a gene implicated in autism. Pääbo is intrigued in particular by a change in a gene that is regulated by the so-called FOXP2 gene, implicated in speech disorders. It is “tempting to speculate that crucial aspects of synaptic transmission may have changed in modern humans,” the team wrote. Thirty-four genes are associated with disease in humans. The list suggests some obvious candidates for gene-expression studies. “The cool thing is that it isn’t an astronomically large list,” Pääbo says. “Our group and others will probably be able to analyze most of them in the next decade or two.”
Back in Leipzig, the mood is upbeat, as researchers pull fossil samples off the shelf to test anew with “Matthias’s method.” First on Pääbo’s list: Neandertal bone samples, to try to produce a Neandertal genome to rival that of the little Denisovan girl.
This story provided by ScienceNow, the daily online news service of the journal Science.
