Category Archives: Genome

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Newswise The human genome project captured the public imagination when its first draft was published 14 years ago this week in the international science journal Nature, but the epigenome may hold the real promise for conquering disease.

While your genome is the same in every cell in your body (except for the gametes), the epigenome is made up of chemical compounds that determine which part of the genome is available for instructing the cells to make proteins. Its why a skin cell, for example, knows its a skin cell.

Medical researchers have high hopes for the knowledge they will gain from the massive effort to map the epigenome now under way under the umbrella of the Roadmap Epigenomics Project of the National Institutes of Health. The latest fruits of this effort appear in the Feb. 18 issue of Nature.

Mapping the epigenome will be extraordinarily useful for people who want to study diseases, said Dr. David A Bennett, the Robert C. Borwell Professor of Neurological Sciences, and director of the Rush Alzheimer's Disease Center.

Cracking the epigenomes complicated codes will allow researchers to understand the a key part of the molecular basis of disease and eventually to control how genes change to cure and hopefully even prevent many common diseases.

The epigenome presents an astonishing number of possibilities for gene expression, all the different permutations and combinations, its complexity orders and orders of magnitude beyond that of the basic genome sequence, Bennett said.

If the Human Genome Project, which got under way in the late 1980s, provided a genetic map of human genome, then the Roadmap Epigenomics Project now under way will annotate that map.

A map only becomes useful to the traveler when its annotated. Where are the towns? Where are the villages? Where are the ports? Bennett said.

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Roadmap Epigenomics Project Releases Latest "Annotations" to the Human Genome

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Newswise Much like mapping the human genome laid the foundations for understanding the genetic basis of human health, new maps of the human epigenome may further unravel the complex links between DNA and disease. The epigenome is part of the machinery that helps direct how genes are turned off and on in different types of cells.

Researchers supported by the National Institutes of Health Common Funds Roadmap Epigenomics Program (http://commonfund.nih.gov/epigenomics/index) have mapped the epigenomes of more than 100 types of cells and tissues, providing new insight into which parts of the genome are used to make a particular type of cell. The data, available to the biomedical research community, can be found at the National Center for Biotechnology Information website (http://www.ncbi.nlm.nih.gov/).

This represents a major advance in the ongoing effort to understand how the 3 billion letters of an individuals DNA instruction book are able to instruct vastly different molecular activities, depending on the cellular context, said NIH Director Francis Collins, M.D., Ph.D. This outpouring of data-rich publications, produced by a remarkable team of creative scientists, provides powerful momentum for the rapidly growing field of epigenomics.

Researchers from the NIH Common Funds Roadmap Epigenomics Program published a description of the epigenome maps in the journal Nature. More than 20 additional papers, published in Nature and Nature-associated journals, show how these maps can be used to study human biology.

What the Roadmap Epigenomics Program has delivered is a way to look at the human genome in its living, breathing nature from cell type to cell type, said Manolis Kellis, Ph.D., professor of computer science at the Massachusetts Institute of Technology, Cambridge, and senior author of the paper.

Understanding epigenomics

Almost all human cells have identical genomes that contain instructions on how to make the many different cells and tissues in the body. During the development of different types of cells, regulatory proteins turn genes on and off and, in doing so, establish a layer of chemical signatures that make up the epigenome of each cell. In the Roadmap Epigenomics Program, researchers compared these epigenomic signatures and established their differences across a variety of cell types. The resulting information can help us understand how changes to the genome and epigenome can lead to conditions such as Alzheimers disease, cancer, asthma, and fetal growth abnormalities.

The value of epigenomic data

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NIH-Supported Researchers Map Epigenome of More Than 100 Tissue and Cell Types

Released: 17-Feb-2015 4:15 PM EST Embargo expired: 18-Feb-2015 7:00 AM EST Source Newsroom: Ludwig Cancer Research Contact Information

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Newswise February 18, 2015, New York, NY Two international teams of researchers led by Ludwig San Diegos Bing Ren have published in the current issue of Nature two papers that analyze in unprecedented detail the variability and regulation of gene expression across the entire human genome, and their correspondence with the physical structure of chromosomes.

We expect that our findings, which describe the interplay of chromosomal structure, regulation and gene expression across a broad array of tissues, will inform research in every branch of mammalian biology and provide information of great value to the study of most human diseases, not least cancer, said Ren.

If the human genome is a recipe book, its chapters are 23 distinct chromosomeseach of which is stuffed, in rough duplicate, into the nucleus of almost all the cells of the human body. But how exactly is that single recipe book read appropriately to build the bodys diverse constituency of cells? Or, for that matter, to generate a community of humans so variegated in their appearance, internal biochemistry and susceptibility to disease?

The two papers address key elements of these riddles. One captures the extent to which the same genesknown as allelesinherited from each parent are expressed at different levels across the genome, so that each version of the gene generates different amounts of the protein it encodes. It links that difference in expression to the distribution and sequence of enhancers on each copy of each chromosome. Enhancers are stretches of DNA that do not encode proteins but can boost gene expression from great distances along the linear strand of DNA.

This is the first time that anyone has looked globally at how gene expression differs between each matching pair of chromosomes across a diverse set of cell types, and our findings are striking, said Ren. Some 30 percent of the gene set we carry is expressed variably across some 20 types of tissues, depending on which parent the alleles came from. Much of that variation appears to come from differences in sequences that regulate the transcriptionor readingof genes.

The other study examines how the three dimensional structure of chromosomes and the distribution of biochemical (or epigenetic) tags that regulate gene expression differ between different types of cells. It also integrates data from the former paper into this analysis to reveal how all of these phenomena interact to control the appropriate expression of the genome. Taken together, these findings add dimension and depth to our understanding of the physical and functional dynamics of the genome, and how its expression is globally regulated to generate the sublime complexity of the human body.

Both studies are invaluable to a deeper understanding of normal biology as well as disease. The data will, for example, help explain precisely why particular parental traits are often so unevenly expressed and why specific deleterious mutations vary in their effects from person to person. They will also serve as a reference that researchers can use to develop a more sophisticated understanding of how gene regulation and chromosomal structure are altered in diseases such as cancer.

Stemming from five years of research, the papers are two of six published this week in Nature that capture the key discoveries of the $300 million Roadmap Epigenomics Program of the US National Institutes of Health. Ren led one of four reference epigenome mapping centers for the program, and his center focused primarily on how DNA and chromatinthe complex of DNA and its protein packaging that makes chromosomesare chemically tagged at specific places to control the expression of genes across the human genome.

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Deconstructing the Dynamic Genome

Much like mapping the human genome laid the foundations for understanding the genetic basis of human health, new maps of the human epigenome may further unravel the complex links between DNA and disease. The epigenome is part of the machinery that helps direct how genes are turned off and on in different types of cells.

Researchers supported by the National Institutes of Health Common Fund's Roadmap Epigenomics Program have mapped the epigenomes of more than 100 types of cells and tissues, providing new insight into which parts of the genome are used to make a particular type of cell. The data, available to the biomedical research community, can be found at the National Center for Biotechnology Information website.

"This represents a major advance in the ongoing effort to understand how the 3 billion letters of an individual's DNA instruction book are able to instruct vastly different molecular activities, depending on the cellular context," said NIH Director Francis Collins, M.D., Ph.D. "This outpouring of data-rich publications, produced by a remarkable team of creative scientists, provides powerful momentum for the rapidly growing field of epigenomics."

Researchers from the NIH Common Fund's Roadmap Epigenomics Program published a description of the epigenome maps in the journal Nature. More than 20 additional papers, published in Nature and Nature-associated journals, show how these maps can be used to study human biology.

"What the Roadmap Epigenomics Program has delivered is a way to look at the human genome in its living, breathing nature from cell type to cell type," said Manolis Kellis, Ph.D., professor of computer science at the Massachusetts Institute of Technology, Cambridge, and senior author of the paper.

Understanding epigenomics

Almost all human cells have identical genomes that contain instructions on how to make the many different cells and tissues in the body. During the development of different types of cells, regulatory proteins turn genes on and off and, in doing so, establish a layer of chemical signatures that make up the epigenome of each cell. In the Roadmap Epigenomics Program, researchers compared these epigenomic signatures and established their differences across a variety of cell types. The resulting information can help us understand how changes to the genome and epigenome can lead to conditions such as Alzheimer's disease, cancer, asthma, and fetal growth abnormalities.

The value of epigenomic data

Researchers can now take data from different cell types and directly compare them. "Today, sequencing the human genome can be done rapidly and cheaply, but interpreting the genome remains a challenge," said Bing Ren, Ph.D., professor of cellular and molecular medicine at the University of California, San Diego, and co-author of the Nature paper and several of the associated papers. "These 111 reference epigenome maps are essentially a vocabulary book that helps us decipher each DNA segment in distinct cell and tissue types. These maps are like snapshots of the human genome in action."

"This is the most comprehensive catalog of epigenomic data from primary human cells and tissues to date," said Lisa Helbling Chadwick, Ph.D., project team leader and a program director at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. "This coordinated effort, along with uniform data processing, makes it much easier for researchers to make direct comparisons across the entire data set."

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Epigenome of more than 100 tissue and cell types mapped

Two dozen scientific papers published online simultaneously on Feb. 18, 2015 present the first comprehensive maps and analyses of the epigenomes of a wide array of human cell and tissue types. Epigenomes are patterns of chemical annotations to the genome that determine whether, how, and when genes are activated.

Because epigenomes orchestrate normal development of the body, and disruptions in epigenetic control are known to be involved in a wide range of disorders from cancer to autism to heart disease, the massive trove of data is expected to yield many new insights into human biology in both health and disease.

The 24 papers describing human epigenomes will appear in print on Feb. 19, 2015 in the journal Nature and in six other journals under the aegis of Nature Publishing Group. Collectively, the papers are a culmination of years of research by hundreds of participants in the Roadmap Epigenomics Program (REP), first proposed in 2006 by academic scientists and key members of the National Institutes of Health. All will be freely available at Nature's Epigenome Roadmap website.

"The DNA sequence of the human genome is identical in all cells of the body, but cell types--such as heart, brain or skin cells--have unique characteristics and are uniquely susceptible to various diseases," said UC San Francisco's Joseph F. Costello, PhD, director of one of four NIH Roadmap Epigenome Mapping Centers (REMC) that contributed data to the REP. "By guiding how genes are expressed, epigenomes allow cells carrying the same DNA to differentiate into the more than 200 types found in the human body."

In cancer research, said Costello, the new data will hasten a merging of genomic and epigenomic perspectives that was already underway. "You've had cancer researchers studying the genome--the role of mutations, deletions, and so on--and others studying epigenomes. They've almost been working on parallel tracks, and they didn't talk to each other all that much. Over the past five or six years, there's been a reframing of the discussion, because the most recurrent mutations in cancer affect epigenomic regulators. So the way mutations in the genome play out is through epigenomic mechanisms, and major pharmaceutical companies now view epigenomes as an important target."

Costello holds the Karen Osney Brownstein Endowed Chair in Neuro-Oncology in the UCSF Department of Neurological Surgery, and is a member of the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC).

The overarching findings of the REP, which include data on 111 distinct human epigenomes from all four REMCs as well as from dozens of individual labs around the world, are covered in a Nature paper for which Manolis Kellis, PhD, of Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, is senior author. In addition to the many implications for normal human biology of "the most comprehensive map of the human epigenomic landscape so far," the authors write, "our data sets will be valuable in the study of human disease, as several companion papers explore in the context of autoimmune disease, Alzheimer's disease, and cancer."

DNA molecules are long, thin double strands containing genes, the discrete units of information that serve as recipes for the protein-making machinery of the cell. In order for DNA molecules to fit into the small space of the cell nucleus, they are compressed and packed like cooked spaghetti, and also wound around spool-like structures called histones. Chemical epigenetic "marks"--the addition of methyl groups in or near genes, and modifications to histones--determine whether genes are available to be transcribed and translated into proteins. Though epigenetic marks are stable, they are reversible, and they can also be altered by environmental factors such as diet, exposure to toxins, and aging. Such changes affect gene expression, which can lead to disease.

The REMC directed by UCSF's Costello included researchers from UCSF; the University of California, Santa Cruz (UCSC); the University of Southern California (USC), Washington University in St. Louis (WUSTL); and Canada's Michael Smith Genome Sciences Centre and the University of British Columbia (UBC), in Vancouver, Canada. The group provided important data to the REP on several cell types, including epigenomes of the normal human placenta, sperm, breast cells, blood cells, fetal and adult brain cells, and skin cells. Misha Bilenki, PhD, a member of Costello's REMC with an appointment at Canada's Michael Smith Genome Sciences Centre, is co-first author of the Nature paper of which Kellis, of MIT and Harvard, is senior author.

A unique contribution of Costello's REMC was the creation, by WUSTL's Ting Wang, PhD, and David Haussler, PhD, and Jim Kent of UCSC, of the Roadmap Epigenome Browser, a web-based tool that gives scientists worldwide open access to the complete data from the REP.

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'Most comprehensive map' of human epigenomes is unveiled

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Newswise Virtually every cell in the body carries an identical genome. But how is it possible that each of the bodys 200 different types of specialized cells in the heart, brain, bone, skin and elsewhere develops from the same DNA instruction book?

As it turns out, reading that instruction book and carrying out its directives are controlled by chemical markers that attach to DNA to activate or silence genes. These chemical markers, known as the epigenome, vary vastly from one cell type to another and, when disrupted, can play a role in the onset of many diseases, from cancer and Alzheimers disease to diabetes and autism. Probing the epigenome could improve scientists understanding of the molecular basis of disease and lead to new treatments.

Now, for the first time, researchers have assembled a comprehensive map of the human epigenome. The mapping, by scientists at Washington University School of Medicine in St. Louis and other institutions, includes detailed descriptions of the epigenetic markers in 111 types of cells and tissues. Partial epigenome mapping is available for many other cell types, and new information will be added as it becomes available.

The research is published Feb. 18 in the journal Nature. More than 20 additional papers, including three by scientists at the School of Medicine, appear simultaneously in other Nature journals to show how epigenetic maps can be used to study human biology.

Weve only scratched the surface of the human epigenome, but this massive resource marks the beginning of an era, said a principal investigator of the epigenome mapping project, Ting Wang, PhD, assistant professor of genetics. We can now begin to describe humans in molecular detail.

We also can look closely at the epigenetic differences between cell types. We dont yet understand what those differences mean or what epigenetic changes drive cell specialization or the initiation of disease. But thats where were headed. This resource opens up many new doors in biology and the biomedical sciences.

The epigenome also lies at the intersection of the genome and the environment. People have little control over their DNA, but epigenomes are dynamic and potentially can be altered by changes in lifestyle, such as diet and exercise, or by pharmaceuticals. That makes the epigenome a critical player in health and disease.

The mapping initiative, referred to as the Roadmap Epigenomics Program, is funded by the National Institutes of Health (NIH) Common Fund.

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Scientists Unveil Map of Human Epigenomes in Effort to Fight Disease

20 hours ago by Adam Thomas UD doctoral student Colin Kern has been annotating the genome of the American alligator, the salt water crocodile and the Indian gharial. Credit: Lindsay Yeager and Danielle Quigley

For the last year and a half, University of Delaware doctoral student Colin Kern has been annotating the genome of the American alligator, the salt water crocodile and the Indian gharial to help researchers from multiple institutions determine the ancestral patterns of evolution among archosaurs, which include crocodilians, dinosaurs and birds.

The results of this study were recently published in the American Association for the Advancement of Science journal Science.

Kern, who is studying in the Department of Computer and Information Sciences, worked on the project with Carl Schmidt, professor in the Department of Animal and Food Sciences, to try to identify where certain genes are located on the sequenced genomes of the three species.

There are two ways to try to determine the location of the genes, Kern said. The first is to predict where the genes are based on current knowledge and the ability to identify sequences of DNA that mark the start of a gene.

The second is to look at known genomic information from other species. "We know that all life evolves, and if you go back far enough, any two species will have a common ancestor," Kern said, explaining that a researcher who finds a gene in a given animal and sees a very similar sequence in a genome just created can infer that it might be the same gene in the newly-studied animal.

Kern said that for each species, he looked for about 20-25,000 genes.

To comb through such massive amounts of data, Kern used two computer programs. The initial gene prediction was done using a program called Augustus and when it came time to assign a function or a name to the genes, he used a tool called the Basic Local Alignment Search Tool (BLAST), which is used to search for similar genes.

Kern said the researchers took the genes that they predicted from the crocodiles, and about which they were not certain, and ran the BLAST program in comparison to chickens to determine the similarities between the genes of the two species.

"We started with the chicken because birds are the most similar group of species to crocodiles, and chicken is probably the most well-studied bird," said Kern. "We were able to assign a nameand along with a name comes the function of what those genes actually areto a lot of the crocodile genes."

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Student uses genome annotation to help study crocodiles, alligators, gharials

Deliriant - Human Genome
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Institut Pasteur - Le 1er genome artificiel de levure - Romain Koszul
La levure, cellule eucaryote, est un organisme relativement facile manipuler gntiquement. Dans cet pisode de Ils font avancer la recherche, Romain Koszul prsente le travail de son...

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Tsunamaru - Daidai Genome [Insane] DoubeTime
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