Category Archives: Genome

Photo: Andrew Brookes/Corbis

In 2005, next-generation sequencing began to change the field of genetics research. Obtaining a persons entire genome became fast and relatively cheap. Databases of genetic information were growing by the terabyte, and doctors and researchers were in desperate need of a way to efficiently sift through the information for the cause of a particular disorder or for clues to how patients might respond to treatment.

Companies have sprung up over the past five years that are vying to produce the first DNA search engine. All of them have different tacticssome even have their own proprietary databases of genetic informationbut most are working to link enough genetic databases so that users can quickly identify a huge variety of mutations. Most companies also craft search algorithms to supplement the genetic information with relevant biomedical literature. But as in the days of the early Web, before Google reigned supreme, a single company has yet to emerge as the clear winner.

Making a functional search engine is a classic big-data problem, says Michael Gonzalez, the vice president of bioinformatics at one such company, ViaGenetics, which was expected to relaunch its platform in March. Before doctors or researchers can use the data, genomic data must be organized so that humans can read and search it. The first step toward that is to put it in a standard form called the variant call format, or VCF. As raw data, a persons complete sequenced genome would take up about 100 gigabytes, so a database that adds the genomes of even 10 patients per day would quickly get out of hand. But VCF files are more compact, requiring only a few hundred megabytes per genome, which helps researchers find the specific variants they want to search in a fraction of the time. Unlike a fully sequenced genome, VCF files point only to where a persons genetic data deviates from the standardthe genome originally compiled by the Human Genome Project in 2001.

With VCF, sifting the genomes themselves for pinpoint mutations isnt the challenge for search engine companies. Most of these companies are allocating their resources toward efforts to seamlessly compile supplementary information about a specific mutation from other databases across the Web, such as the biomedical research archive PubMed or various troves of electronic medical records. Many of these tools have finely tuned algorithms that prioritize the results by credibility or relevance. You want to be able to pull together the information known about a mutation in that position [of the genome] and quickly make an assessment, says David Mittelman, the chief scientific officer for Tute Genomics, based in Provo, Utah, another company designing a genetic-search engine.

In an effort to expand the information that can be attached to a genome under examination, ViaGenetics, based in Miami Beach, Fla., is making its newly updated platform useful for researchers who want to collaborate across institutions. With ViaGenetics tools, researchers can make their data available to other users, so other people can come across these projects, request access, and form a collaboration, Gonzalez says. It helps people connect the dots between different researchers and institutions. This is especially helpful for smaller labs that may not have very extensive genome databases or for researchers from different universities working to decode the same mutation.

Although the genomic-search industry is now focused on serving scientists, that might not always be the case. Mittelman envisions that Tute Genomics could eventually serve consumers directly. People are already demanding information about their genomes just to understand themselves better, Mittelman says, but most companies dont yet consider the average person to be their primary customer. In order to make that shift, the tool will have to be even more intuitive and user-friendly. Fire-hosing someone with data thats not easy to interpret, or using terminology thats not standardized, has the potential to confuse people, he says. Privacy is also a major concern for the average user; the information that Tute users upload isnt stored permanently, Mittelman says, but users will need extra reassurance if the platform becomes available to the lay public.

And a further evolution of the industry is in the offing. Both ViaGenetics and Tute are hoping to be able to run the entire process in-housefrom the initial DNA sequencing to the presentation of final searchable results to users. The market for analyzing and interpreting genomic data is very fragmented, like the computer industry in the 1990s, where you had to go to separate providers to buy a video card or a motherboard and then try to put it together, Mittelman says. Soon this field will consolidate, as the computer industry did.

This article originally appeared in print as A Google for DNA.

Read the original post:
The Race to Build a Search Engine for Your DNA

Peter Campbell The leukaemia genome
Why Don #39;t We All Have Cancer? Animated Introduction to Cancer Biology (Full Documentary) Teen Cancer Stories | UCLA Daltrey/Townshend Teen Young Adult Cancer Program Liezl loses the ...

By: specific part of the body

View post:
Peter Campbell The leukaemia genome - Video

Using a technique that cuts out unwanted copies of a genome to improve the beneficial properties of a compound, researchers working at the University of Illinois College of Agricultural, Consumer, and Environmental Services (ACES) claim to have produced a yeast that could vastly increase the quality of wine while also reducing its hangover-inducing properties.

"Fermented foods such as beer, wine, and bread are made with polyploid strains of yeast, which means they contain multiple copies of genes in the genome," said Associate Professor of microbial genomics at the University of Illinois, Yong-Su Jin. "Until now, its been very difficult to do genetic engineering in polyploid strains because if you altered a gene in one copy of the genome, an unaltered copy would correct the one that had been changed,"

So the researchers developed what they call a "genome knife," which allowed them to slice across multiple copies of a target gene until all the copies were cut, thereby making it impossible for any remaining genomes to correct any altered ones.

After being completely cut, the enzyme RNA-guided Cas9 nuclease was then employed to carry out precise metabolic engineering on strains of polyploid Saccharomyces cerevisiae, a species of common yeast instrumental in winemaking, bread baking, and beer brewing.

This newly-modified strain, the team believes, is a breakthrough of "staggering" proportions. The applications of this compound possibly range in the thousands, given the ubiquity of the species of yeast and its use in a myriad different industries.

"Wine, for instance, contains the healthful component resveratrol, said Associate Professor Jin. "With engineered yeast, we could increase the amount of resveratrol in a variety of wine by 10 times or more. But we could also add metabolic pathways to introduce bioactive compounds from other foods, such as ginseng, into the wine yeast. Or we could put resveratrol-producing pathways into yeast strains used for beer, kefir, cheese, kimchee, or pickles any food that uses yeast fermentation in its production."

But more than this, if winemakers were to clone this new enzyme, then they could use it to improve malolactic fermentation (the conversion of bitter malic acid, naturally present in freshly pressed grapes, into softer-tasting lactic acid) to produce a consistently smoother wine while also removing the toxic byproducts that can cause hangovers.

The scientists see the capability of their genome knife in this situation as an absolute must in engineering the extremely precise engineered mutations required to achieve this improvement in wine fermentation.

"Scientists need to create designed mutations to determine the function of specific genes," said Jin. "Say we have a yeast that produces a wine with great flavor and we want to know why. We delete one gene, then another, until the distinctive flavor is gone, and we know weve isolated the gene responsible for that characteristic."

Optimistically, the researchers also believe that their nascent technology could make genetic engineering and genetically modified organisms more palatable to the wider community.

See original here:
Engineered yeast could increase nutritional value of wine while reducing hangovers

Evidence is growing that your DNA sequence does not determine your entire genetic fate. Joseph Nadeau is trying to find out what accounts for the rest.

Somethings missing: Geneticist Joseph Nadeau has been finding examples of what he calls funky genetic effects that could help explain the mystery of missing heritability.

What we know about the fundamental laws of inheritance began to take shape in a monastery garden in Moravia in the middle of the 19th century, when Gregor Mendel patiently cross-bred pea plants over the course of several years, separated the progeny according to their distinct traits, and figured out the mathematical foundations of modern genetics. Since the rediscovery of Mendels work a century ago, the vocabulary of Mendelian inheritancedominant genes, recessive genes, and ultimately our own eras notion of disease geneshas colored every biological conversation about genetics. The message boils down to a single premise: your unique mix of physiological traits and disease risks (collectively known as your phenotype) can be read in the precise sequence of chemical bases, or letters, in your DNA (your genotype).

But what ifexcept in the cases of some rare single-gene disorders like Tay-Sachs diseasethe premise ignores a significant portion of inheritance? What if the DNA sequence of an individual explains only part of the story of his or her inherited diseases and traits, and we need to know the DNA sequences of parents and perhaps even grandparents to understand what is truly going on? Before the Human Genome Project and the era of widespread DNA sequencing, those questions would have seemed ridiculous to researchers convinced they knew better. But modern genomics has run into a Mendelian wall.

Large-scale genomic studies over the past five years or so have mainly failed to turn up common genes that play a major role in complex human maladies. More than three dozen specific genetic variants have been associated with type 2 diabetes, for example, but together, they have been found to explain about 10 percent of the diseases heritabilitythe proportion of variation in any given trait that can be explained by genetics rather than by environmental influences. Results have been similar for heart disease, schizophrenia, high blood pressure, and other common maladies: the mystery has become known as the missing heritability problem. Francis Collins, director of the National Institutes of Health, has sometimes made grudging reference to the dark matter of the genomean analogy to the vast quantities of invisible mass in the universe that astrophysicists have inferred but have struggled for decades to find.

Joseph H. Nadeau has been on a quest to uncover mechanisms that might account for the missing components of heritability. And he is finding previously unsuspected modes of inheritance almost everywhere he looks.

Nadeau, who until recently was chair of genetics at Case Western Reserve University in Cleveland and is now director of research and academic affairs at the Institute for Systems Biology in Seattle, has done studies showing that certain traits in mice are influenced by specific stretches of variant DNA that appeared on their parents or grandparents chromosomes but do not appear on their own. Transgenerational genetics, as he calls these unusual patterns of inheritance, fit partly under the umbrella of traditional epigeneticsthe idea that chemical changes wrought by environmental exposures and experiences can modify DNA in ways that either muffle a normally vocal gene or restore the voice of a gene that had been silenced. Researchers have begun to find that these changes are heritable even though they alter only the pattern of gene expression, not the actual genetic code. Yet its both more disconcerting and more profound to suggest, as he does, that genes an ancestor carried but didnt pass down can influence traits and diseases in subsequent generations.

Consider the results of an experiment Nadeau and his colleague Vicki R. Nelson published last August. They created an inbred strain of mice and then compared two sets of females that were genetically identical except for one small difference: one set had a father whose Y chromosome came from another strain of mouse and contained a different set of genetic variants. That shouldnt have affected the daughter mice at all, because females dont inherit the Y chromosome. But the presence of that uninherited DNA in the previous generation exerted a profound effect on many of the more than 100 traits tested in the two sets of female offspring, whose own DNA was exactly the same. These results, Nelson and Nadeau concluded, suggest that transgenerational genetic effects rival conventional genetics in frequency and strength.

In a separate but similarly unsettling line of experiments, Nadeau and his collaborators are finding that the impact of any given gene depends on all the other genes surrounding it. Nadeau is hardly the only scientist to identify these complex gene-gene interactions, but he and his colleagues have created a unique set of genetically engineered mice that is giving them and other scientists unprecedentedly precise tools for dissecting these situational genetics to show how the variants in a genes molecular neighborhood affect the way it behaves.

Findings like these, taken together, could shed light on the missing-heritability problem, but at the cost of upending the dominance of traditional Mendelian ideas about how inheritance works. Sitting on the outside deck of the Institute for Systems Biology one recent afternoon, munching on a sandwich as seaplanes descended toward the skyline of Seattle, Nadeau recalled giving a talk about all this at a conference several years ago and discovering afterward that a prominent Ivy League geneticist in attendance, whom he declined to name, simply couldnt get the heretical ideas out of his head. He came up to me after the talk, Nadeau recalled, and said, This cant be true in humans. I ran into him at breakfast the next day and he said, This cant be true in humans. And then when the meeting was over, I ran into him at the airport, and he came up to me and said, This cant be true in humans. Or as another leading genome scientist once told Nadeau at a meeting in Europe, If transgenerational effects happen in humans, were screwed.

More:
The Genome's Dark Matter

If wine tends to give you a hangover, science may have a solution, and it starts with a "genome knife." The phrase refers to an enzyme called RNA-guided Cas9 nuclease that's able to knock down a longstanding hurdle to genetic engineering in fermented foods, a researcher at the University of Illinois explains in a press release.

It's a little complicated, but the strains of yeast that ferment wine (along with beer and bread) are "polyploid" strains. Those strains "contain multiple copies of genes in the genome," says Yong-Su Jin, whose study was published in Applied and Environmental Microbiology.

The difficulty comes into play when you try to alter a gene in one copy of the genome. Essentially, you can't: "An unaltered copy would correct the one that had been changed." The enzyme fixes that problem.

It allows the genetic engineering of polyploid strains, specifically Saccharomyces cerevisiaewhich you're more likely to know as baker's yeast, Jove notes. Researchers are calling the engineered result a "jailbreaking" yeast.

Engineered yeast could make wine healthier by boosting the amount of a nutrient called resveratrol "by 10 times or more," Jin notes. As for post-booze headaches, the "genome knife" could act on what's known as malolactic fermentation, which can result in hangover-inducing toxic substances.

That's good news, though Medical Daily reports that the variety of factors leading to hangovers likely means such a product wouldn't get rid of them completely.

(It's not just the genetics involved in winemaking that affect your hangover risk: Your own genes do, too, according to research last year.)

This article originally appeared on Newser: Scientists Find a Way to Cut Wine Hangovers

Link:
Researchers find a way to cut wine hangovers

Let #39;s Play FF9 part 57: Genome #39;s Purpose
So Zidane meets Garland the Creator of the Genome. We now learn about Zidane #39;s purpose, and some one else as well.

By: Aceofspadesth

Continued here:
Let's Play FF9 part 57: Genome's Purpose - Video

A recently published global genome study that used the data-intensive Gordon supercomputer at the San Diego Supercomputer at the University of California, San Diego, has researchers rethinking how avian lineages diverged after the extinction of the dinosaurs.

The four-year project, called the Avian Genome Consortium and published in the journal Science, resulted in a new family "tree" for nearly all of the 10,000 species of birds alive today by comparing the entire DNA codes (genomes) of 48 species as varied as parrot, penguin, downy woodpecker, and Anna's hummingbird. The massive undertaking, started in 2011, involved more than 200 researchers at 80 institutions in 20 countries, with related studies involving scientists at more than 140 institutions worldwide.

The genome-scale phylogenetic analysis of the 48 bird species considered approximately 14,000 genes. This presented computational challenges not previously encountered by researchers in smaller-scale phylogenomic studies based on analyses of only a few dozen genes. The inclusion of hundreds of times more genetic data per species allowed the researchers to realize the existence of new inter-avian relationships.

"Characterization of genomic biodiversity through comprehensive species sampling has the potential to change our understanding of evolution," wrote Erich Jarvis, associate professor of neurobiology at the Howard Hughes Medical Institute at Duke University and the study's principal investigator, in an introduction to a special issue of the journal Science containing eight papers from the study. An additional 20 papers generated by the study were simultaneously published in other journals.

"For 50 species, more than 10 to the power of 76 possible trees of life exist. Of these, the right one has to be found," said Andre J. Aberer, with the Heidelberg Institute for Theoretical Studies (HITS), in a news release at the time of the study's publication in Science. "For comparison: About 10 to the power of 78 atoms exist in the universe."

Many of the computations were done on SDSC's Gordon supercomputer by Aberer with the assistance of SDSC Distinguished Scientist Wayne Pfeiffer. They ran a new code called ExaML (Exascale Maximum Likelihood) to infer phylogenetic trees using Gordon soon after it debuted in 2012 as one of the 50 most powerful supercomputers in the world.

Developed by Alexandros Stamatakis, head of the Scientific Computing Group at HITS, ExaML couples the popular RAxML search algorithm for inference of phylogenetic trees using maximum likelihood with an innovative MPI parallelization approach. This yields improved parallel efficiency, especially on partitioned multi-gene or whole-genome data sets.

"I had previously collaborated with Alexis on improving the performance of RAxML," said Pfeiffer. "He described the goals of the Avian Genome Consortium, and we agreed that Gordon, with its just-released fast processors, could provide much of the computer time needed for this ambitious project. In the end, more than 400,000 core hours of computer time were consumed on Gordon."

"After doing initial analyses on our institutional cluster, we rapidly realized that comprehensive analysis of the more challenging data sets being considered would require supercomputer resources," said Aberer. "Access to Gordon was thus invaluable for achieving results in a timely manner."

In all, high-performance computing (HPC) resources at nine supercomputer centers were used to analyze the complete genomes because of the scope of the undertaking. In addition to Gordon, several other U.S.-based supercomputers that are or have been part of the National Science Foundation's eXtreme Science Engineering and Discovery Environment (XSEDE) were used: Ranger, Lonestar, and Stampede at the Texas Advanced Computing Center (TACC) at the University of Texas at Austin; and Nautilus at the National Institute of Computational Sciences (NICS) at the University of Tennessee.

Read the original post:
Researchers rethink how our feathered friends evolved

Maybe it was the Jolie effect. Or you want to find out if youre carrying a silent genetic mutation that could be passed on to a child. Or perhaps youre just really hoping you can blame your DNA for how awful cilantro tastes. Whatever the reason, youre interested in finding out something about your genome. Now what?

Though consumer genetic testing and personal genome sequencing are still nascent fields, every indication suggests that the public will have a virtually insatiable appetite for genetic data. And as scientists get better at establishing links between DNA and diseases or specific traits, that demand will only increase.

But are we ready for this data? Sure, massive-scale scientific instruments can churn out DNA information at breakneck pace, but is the rest of the scientific, medical, and social infrastructure in place to analyze, interpret, and protect it? At the moment, the short answer is no. But this is a major focus for the biomedical community right now, and improved solutions are being developed almost daily.

(Image via Shutterstock)

At the moment, there are several ways to get your hands on your own genetic data. Services like 23andMe and Ancestry.com offer direct access to basic genealogical information that can be gleaned from your genome. By going through a physician or genetic counselor, you can get targeted clinical resultssuch as your carrier status for a certain disease or whether you have a genetic variant that makes you more susceptible to canceror even your whole genome sequence. (As we reported earlier this year, genetic counselors may be more likely to order a DNA test on your behalf than a physician. Heres a list of companies offering personal genomic tests.)

For the most part, providers of this information will attempt to offer a useful interpretation of your data. A hereditary cancer test or carrier screening test will come back indicating positive (increased risk) or negative (normal risk). Ancestry testing will show on a map where your ancestors came from, likely with percentages for how much different regions contributed to your DNA. Even if you get your whole genome sequenced, part of the service will include talking with a genetic counselor to go over any major findings. Given how early we are in the genomic era, there are relatively few major findings; most people who get their genome sequenced today wont learn anything truly life-changing.

Its worth noting that the interpretation you get may not be complete. For example, if youre clinically tested for a mutation linked to heart disease, the result you get backan interpretation of whether your genetic code places you at increased risk for heart diseasemay not mention it if one of the genes analyzed also happens to reveal your risk for developing Alzheimers disease.

Most people who get genetic results today, especially if they go through a medical professional, stop the journey when they learn the answer to their specific question. But some people dig deeper, which is possible with low-cost services such as Promethease. You upload your genetic data, and these services churn through it to deliver more information. In our earlier heart disease example, these kinds of services might alert you to your Alzheimers risk even though the clinical lab didnt. This kind of offering has great value, but comes with a significant caveat emptor: you may learn something you didnt want to know.

View original post here:
How To Get And Protect Your Genetic Data

Questions that Will Affect the Rest of Your Life: What the Genome Tells Us (2000)
The Human Genome Project (HGP) is an international scientific research project with the goal of determining the sequence of chemical base pairs which make up human DNA, and of identifying and...

By: The Film Archives

Read the original here:
Questions that Will Affect the Rest of Your Life: What the Genome Tells Us (2000) - Video

Contact Information

Available for logged-in reporters only

Newswise Life science researchers at Virginia Tech have accelerated a game-changing technology that's being used to study one of the planet's most lethal disease-carrying animals.

Writing in this week's Proceedings of the National Academy of Sciences, researchers revealed an improved way to study genes in mosquitoes using a genome-editing method known as CRISPR-Cas9, which exploded onto the life science scene in 2012.

Editing the genome of an organism allows scientists to study it by deleting certain genes to observe how the organism is affected, or even to add new genes. The new technique makes the editing process more efficient and may accelerate efforts to develop novel mosquito-control or disease-prevention strategies.

"We've cut the human capital it takes to evaluate genes in disease-carrying mosquitoes by a factor of 10," said Zach N. Adelman, an associate professor of entomology in the College of Agriculture and Life Sciences and a member of the Fralin Life Science Institute. "Not a lot of research groups have the resources to spend four months working with up to 5,000 mosquito embryos to investigate a gene that may ultimately have no bearing on their work. Now they can potentially do the same investigation in a week."

Mosquitoes transmit pathogens that cause malaria, dengue fever, and other high-impact diseases. In 2013, Malaria killed an estimated 584,000 people, most of them young children, according to the World Health Organization. Bill Gates, the co-founder of Microsoft and a philanthropist who supports social and health causes, has called the mosquito the world's deadliest animal.

"The mosquito is incredibly important as far as transmission of disease," said Kevin M. Myles, an associate professor of entomology in the College of Agriculture and Life Sciences and a member of the Fralin Life Science Institute. "With this model, any scientist asking a question about a mosquito phenotype can now find its genetic cause. That's important for basic research into mosquito biology and applied research to control disease-vector mosquitoes."

The scientific community has long rallied to fight mosquito-borne diseases.

"I am excited by the paper," said Laura C. Harrington, a professor and the chairwoman of entomology at Cornell University, who was not involved in the research. "We are desperately in need of faster and more efficient ways to transform mosquitoes. This single hurdle is holding the entire field back from making the discoveries that will lead to novel and effective approaches to mosquito and, consequently, disease control."

Continued here:
Virginia Tech Scientists Streamline Genome-Editing Tool to Thwart 'Deadliest' Animal