Category Archives: Genome

Looping the genome: How cohesin does the trick Science Daily Defined genome-sequences that were previously located far apart are now next to each other and can interact to regulate gene expression. In Nature online this week, IMP-researchers publish data that support the existence of such a mechanism. First ...

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Looping the genome: How cohesin does the trick - Science Daily

NEW YORK, April 24, 2017 /PRNewswire/ --Dante Labs announced today the offer of whole genome sequencing (WGS) and interpretation at only EUR 850 (ca. $900). While American individuals have been able to access WGS at $1,000, this innovation marks the first time Europeans can access WGS below EUR 1,000.

The sequencing includes bioinformatics analysis and interpretation, which are crucial to leveraging genetic information to make informed decisions about disease monitoring, prevention, nutrition, exercise, health monitoring and more.

WGS is run at 30X coverage, which makes the achievement even more impressive.

Dante Labs has chosen a select list of partners to develop DNA sequencing services that are "accessible to everyone ... By leveraging only the world's best genetic technologies, we ensure that our customers have access to the best in the world of genetics", says Dante Labs co-founder Andrea Riposati. "Genetics has seen tremendous developments in the last decade. Just think that the first whole genome sequencing cost north of $2.4 billion. For too long, only [a] few people could benefit from the impact of genetic research. It's healthcare, so I say it is important [that] everyone benefits from it. The key to empower[ing] everyone with high-quality, advanced genetics is to decrease the price. By integrating in the value chain, removing unnecessary intermediaries, developing synergies with strategic partners and leveraging economies of scale, we are able to offer whole genome sequencing at only EUR 850".

Dante Labs offers a suite of direct-to-consumer DNA tests, including BRCA1 and BRCA2 sequencing, whole exome sequencing and common hereditary cancer testing.

Media Contact: FrancescoPennelli Phone: +39.320.603.0072 Email: francesco@dantelabs.com

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Dante Labs Offers EUR 850 Whole Genome Sequencing and ... - PR Newswire (press release)

Modern evolutionary science, including the science of genetics is based on the hypothesis that most if not all things can be explained in a natural way through empirical research. A theist evolutionist will simply say that evolution is the way God works things. Suppose however that God is not like a watchmaker who creates a watch, winds it up, and leaves it to the empirical parts to do their jobs their after? Suppose God is constantly involved not merely in human history but in all things great and small. Suppose the designer constantly has his hand on the design, and makes changes and modifications? Suppose he designed human beings to be like other higher order creatures so that humans would feel some kinship with them, and take care of them, and be good governors of Gods creation? Evolution is a theory that leave God constantly out of the equation, or alternately simply says this is the natural mechanism God chose to accomplish things.

The same problems arise in applying this sort of information to the historical figures of Adam and Eve as arises in the neuro-scientific discussions about the mind and the brain, where the assumption is that human beings are psychosomatic wholes, and as such, when the body goes the whole person dies. There is no human spirit, human personality that survives death. Of course, no scientist has gone to the other side of death and done an empirical study of whether there might be spirits of the departed in heaven or elsewhere. The assumption again is this world, this life, these natural processes, like evolution are all there is, and so a theory which explains some things, is globalized to explain everything, including ruling out ongoing divine action in the natural and human worlds, never mind ruling out the afterlife.

My point by drawing attention to these two differing attempts at discussing science and the Bible together is that science often has to extrapolate or theorize from the known to the unknown to come up with a purely materialistic and empirical explanation for things.

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Adam and the Genome-- Part Five - Patheos - Patheos (blog)

The winner of the World's Most Interesting Genome competition has been announced and a pure bred dingo called Sandy has ended up on top.

The competition was tough, with Sandy beating a 'solar-powered' sea slug, an explosive beetle, and a deadly Asian snake to take out the top spot.

Sandy and her siblings were found as abandoned three-week old pups in the Australian desert, two years ago.

Barry Eggleton

Being a wild-born pure Australian desert dingo is a pretty big deal most dingos have interbred with wild dogs and domestic dogs, so it makes Sandy rare.

"Sandy is truly a gift to science. As a rare, wild-born pure dingo, she provides a unique case study," said project leader Bill Ballard, from the University of New South Wales (UNSW).

"Pure dingoes are intermediate between wild wolves and domestic dogs, with a range of non-domesticated traits."

"So sequencing Sandy's genome will help pinpoint some of the genes for temperament and behaviour that underlie the transition from wild animals to perfect pets," he added.

Let's take a look at the rest of the finalists:

Elysia timida the "solar-powered" sea slug

Parent Gry/Wikimedia

Elysia timida is a sea slug that can 'steal' and use the chloroplasts of the algae it consumes as food.

Chloroplasts are the parts of plants that undergo photosynthesis a process that takes light and turns it into energy.

Currently scientists don't understand how the slugs maintain chloroplasts typically only used by plants, but it allows them to survive for months without eating.

Nesoenas mayeri, the Pink Pigeon

The pink pigeon is interesting for more than just its colour.

As a species that nearly became extinct in the 1990's (having only 16 wild birds remaining), they managed to bounce back, with records showing there are now more than 400 individuals.

But the pink pigeon isn't out of the woods yet with low genetic diversity, over 60 percent of baby birds dying due to infection, we need to understand as much as we can about these guys to make sure they don't end up like their dodo cousins.

Tropidolaemus waglerithe "sexually dimorphic" Temple Pit Viper

The temple pit viper is pretty badass.

Not only does it have unique toxins in its venom not found anywhere else in the world, but its sexual characteristics also is quite different to most snake species.

Temple pit viper males are small and green, while the females are 10 times the male's size and beautifully coloured.

Plus you can find these vipers in the Snake Temple in Malaysia, which is one of the only temples of its kind in the whole world.

Brachinus elongatulusthe "explosive" bombardier beetle

The bombardier beetle is basically the mad scientist of the bug world.

With explosive chargers of toxic chemicals that explode out of the bug at temperatures over 100 degrees Celsius (212 degrees Fahrenheit) they can definitely hold their own in a fight.

It also doesn't seem to hurt itself in the process.

The beetle itself has been baffling evolutionary geneticists for decades with how such a creature managed to evolve at all. One evolutionary slip-up and the bug itself would explode.

It's totally worth checking out this video below to find out more:

But despite all this notable wildlife, we're excited that Sandy came first.

The company behind the competition, PacBio, will now sequence the DNA with their extremely precise machine to investigate the secrets of Sandy's genome.

We're looking forward to seeing what the UNSW team discovers.

UNSW Science is a sponsor of ScienceAlert. Find out more about their world-leading research.

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This Dingo Has Won the Title of the World's Most Interesting Genome - ScienceAlert

Its been a couple of years since the genome editing tool CRISPR first hit the headlines. And talk of its potential to cure all manner of diseases, create superhumans and bring dinosaurs back from the dead has followed.

But among that speculation, one area of medicine has been quick to pick up the technology and is now leading the way in early clinical trials.

In this second post in our series taking a closer look at CRISPR, we explore its potential for new developments in cancer immunotherapy.

Immunotherapy can take a range of forms. Some experimental approaches use viruses that kill cancer cells and alert the immune system to attack. Others involve giving patients drugs that release the brakes on immune cells to target cancer. And some use specially engineered immune cells that when injected into a patient have the potential to hunt out and kill cancer cells.The aim of immunotherapy treatments is to alert the bodys immune system to cancer, so that its better equipped to recognise and fight the disease.

In each of these cases, scientists need to be able to understand and fine-tune the bodys complex immune system. And some are turning to CRISPR for help.

Dr Martin Pule, a clinical senior lecturer in haematology at UCL, says that genome editing techniques such as CRISPR have quickly become part of the tool-kit for researchers like him.

In the past, many of the technical problems around introducing new genes into cells were worked out, but we didnt have an easy way of efficiently and precisely disrupting existing genes, he says. New genome editing technologies changed all that.

By using CRISPR, scientists are able to tweak specific genes in viruses or the bodys own immune cells, and so make them behave differently.

Researchers have been able to do this before using similar techniques, but the excitement around CRISPR is that this can be done much quicker, cheaper and more precisely than ever before.

Genome editing techniques have been used in people to treat cancer and other diseases before.

There was lots of excitement when news broke in 2015 of a 1 year old girl with acute lymphoblastic leukaemia (ALL) being treated with a similar editing technique known as TALENs, after all other treatments had failed.

She received a transplant of cancer-fighting immune T cells from a donor, which had been tweaked in the lab to give them 2 new characteristics.

Normally, the donated cells would see their new environment as foreign and attack the patients healthy cells, but genes that control this process were turned off. The T cells would also be susceptible to attack from the anti-cancer drugs that the baby was receiving, and so modifications were made to protect them.

She responded well to the treatment, and another infant received a similar therapy.

Following in the footsteps of its cousin TALENs, CRISPR itself has moved on from the lab to clinical trials. Late last year, a Chinese group became the first to use CRISPR-edited cells in humans.

Find out more:9 burning questions about CRISPR genome editing answered

The team took immune cells from a patient with an aggressive lung cancer and edited them in the lab. This editing deactivates a gene that allows tumours to put the brakes on these immune cells, preventing them from attacking cancer cells.

By switching off the gene, which produces a molecule on the cells surface called PD-1, the full force of the bodys immune system is released, helping it clear the tumour. Drugs that target PD-1 are among the much-lauded immunotherapy treatments already showing promise in advanced melanoma and lung cancers. So theres a lot of hope that CRISPR may provide another step forward here too.

10 patients will be involved in the early-stage Chinese trial, and it will look at whether the treatment is safe, rather than testing effectiveness.

The scientists are also hoping to start clinical trials using CRISPR to treat bladder,prostateandkidney cancers. Its also positive news that both blood cancers and solid tumours appear to be responding to various immunotherapy approaches, as different challenges are faced in treating these diseases.

One clever immunotherapy trick fuses together 2 components of the immune system with different jobs.

Chimeric antigen receptor (CAR) T cells are a mix of an antibody molecule, which can home in on a specific target on tumour cells, fused to a T cell that provides the knock-out blow to the cancer cell.

Weve blogged before about how these engineered cells work, and small trials in 2011 caused lots of excitement. But one of the latest updates is that using CRISPR instead of older genome editing techniques might supercharge these CAR T-cells even further.

The older technology is less precise and can result in the genes mistakenly being inserted at random locations in the cells DNA. The knock-on effect is that the engineered cells might be less effective or unintended side-effects could be introduced.

But a US-based group found that CRISPR improved the precision with which the modified gene was inserted into T cells. Their research suggests that the cells were then more potent in their fight against leukaemia in mice because they had more stamina. The researchers are now hoping to test these findings in people.

Cancer cells are relentless in their attempt to evade treatment, so we need CAR T cells that can match and outlast them, Dr Michel Sadelain, the researcher leading the study at Memorial Sloan Kettering Cancer Center, said at the time.

Find out more:Engineering a cancer-fighting immune super soldier

Its findings like these that will hopefully make engineered immune cell treatments better and kinder in the future, though they arent yet the Holy Grail.

In one kind of leukaemia called B-ALL, almost 100% of children who received engineered T cells responded, despite having a disease which had become resistant to all standard treatments, says Pule.

This suggests that, in some circumstances, there may not be an upper limit on who may respond to these treatments. But achieving this in other cancers will take further fine-tuning. In other diseases, such as another kind of blood cancer called DLBCL, the response rates are more like 60%.`

This reflects the fact that a good CAR T cell product is hard to make, or that there are factors inside the tumour making the T cells less effective, Pule adds.

Lots of the progress using CAR T cells has so far been in blood cancers rather than solid tumours, which have even tougher conditions.

Because CRISPR allows scientists to do lots of small-scale tinkering, this is a rapidly developing field and researchers are trying to find solutions.

Right now a lot of people are asking why theres this response gap between DLBCL and B-ALL. Can we edit something in the CAR T cell, or put something extra in which will increase the response rates?

One reason might be that the tumour lives in a hostile environment that stops the engineered T-cells ability to attack the cancer cells. One way around this is to delete the molecules on T cells that coordinate the stop messages from the microenvironment.

This strategy looks like it might be quite effective and could increase the number of patients who respond, says Pule.

Some of the research thats taken place since CRISPR burst onto the scene has also raised more questions than answers. The immune system is a powerful and complicated machine, and we dont yet understand how to control it.

Not all of these treatments have been as successful as hoped. As well as varying response rates, they can also cause serious side effects, including, in rare cases, death.

There have been recent reports of patients with bladder cancer whose tumours increased in size after immunotherapy treatment, although this has caused some debate among researchers. Side effects including extreme fever or organ damage have also been well documented in clinical trials.

In the US, a total of 5 patients died following treatment with an experimental CAR T cell therapy for ALL. The clinical trial was paused after 3 people died, and then stopped after 2 more deaths.

While this is very rare, its clear that as well as working to make treatments more effective in more people, researchers also need to look at how they can reduce side effects.

Similar problems were seen in the past in the early days of treatments such as combination chemotherapy, before they were refined.

Pule points to how scientists are already using genome editing to increase safety. For example, in many cases, it isnt possible to engineer a patients own T cells and so cells from a donor are needed.

But this raises some challenges.

The donor T cells might attack the recipient causing graft-versus-host disease, says Pule. Graft-versus-host disease is a condition where the donor cells see their new environment as foreign and attack it. If we remove a specific molecule in the donor T cells using gene-editing technology, we can reduce the chance of this happening.

This is how the two infants with ALL were treated.

Like many new technologies, CRISPR was greeted with excited fanfare in some parts, and a more cautious realism is now settling in.

Its clear that CRISPR opens up so many doors for immunotherapy and lets researchers go further, more easily than ever before. But as the technology is understood better, its limitations and challenges also come into focus.

The third part of our CRISPR series will take a look at what the future might hold for CRISPR and cancer research.

Michael

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CRISPR genome editing and immunotherapy the early adopter ... - Cancer Research UK (blog)

Sandy Maliki, a pure desert dingo and winner of the World's Most Interesting Genome competition, will have her DNA decoded.

Meet Sandy the dingo, owner of the world's most interesting genome.

The wild-born, pure Australian desert dingo recently took first place in the World's Most Interesting Genome competition, and will have her DNA decoded thanks to the Pacific Biosciences SMRT Grant Program. The grant provides genome sequencing for "a particularly fascinating plant or animal."

In a public poll, Sandy secured 41 percent of the votes to beat out a pit viper, a solar-powered sea slug, an explosive beetle and a pink pigeon for the top prize.

Sandy's DNA could offer researchers insight into the process of domestication, according to project leader Bill Ballard, an evolutionary biologist at the University of New South Wales (UNSW). [10 Things You Didn't Know About Dogs]

"Sandy is truly a gift to science. As a rare, wild-born pure dingo, she provides a unique case study," Ballard, who submitted the bid to sequence Sandy's DNA, said in a statement. "Pure dingoes are intermediate between wild wolves and domestic dogs, with a range of non-domesticated traits. So sequencing Sandy's genome will help pinpoint some of the genes for temperament and behavior that underlie the transition from wild animals to perfect pets."

Dingoes were not domesticated by indigenous peoples after being introduced to Australia about 5,000 years ago, according to the UNSW researchers. However, interbreeding with wild and domestic dogs has made pure wild dingoes a rare find.

At 3 weeks old, Sandy, her sister and her brother were discovered in poor health in the Australian desert, and their parents could not be found. The wild pups were taken in by local animal lovers Barry and Lyn Eggleton, who have hand-reared the dingoes since their rescue in 2014.

The sequencing of Sandy's pure-dingo DNA will test of Charles Darwin's 1868 theory on the process of domestication. Darwin theorized that domestication could occur via unconscious selection (a result of nonintentional human influence) and artificial selection (breeding for specific traits).

"This project will reveal the DNA changes between wolves and dingoes (unconscious selection) and dingoes and dogs (artificial selection)," Ballard said in the statement.

Beyond its evolutionary value, sequencing Sandy's genome will give researchers a better understanding of dingo genetics, Ballard said. This could aid conservation efforts to protect the wild canines and improve tests for their genetic purity, he added.

Original article on Live Science.

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This Dingo Has the World's Most Interesting Genome - Live Science

Thomas Weaver, Ph.D., Chief Executive Officer of Congenica, said: "Sapientia is already used extensively throughout the NHS in the UK as well as by clinical scientists providing reports for the 100,000 Genomes Project. Without a diagnosis, it is difficult to select the most appropriate treatment plan for a patient or make a prognosis of what the likely outcomes may be. Edico shares our vision of transforming healthcare by developing easy to use, highly automated genomics analysis solutions, and by combining our complementary technologies we aim to accelerate the clinician's ability to use genomics to diagnose a patients' disease, and make this available on a global basis."

Edico's DRAGEN Bio-IT processor has been assessed as part of University College London's (UCL) Rapid Paediatric Sequencing Project (RaPs), a pilot aimed at evaluating the use of rapid whole genome sequencing (WGS) for rare diseases in an intensive care clinical setting.

Phil Beales, Professor of Medical and Molecular Genetics at UCL, said: "For children with rare diseases and their parents, answers cannot come quickly enough. Faster answers mean less time finding a diagnosis and more time making decisions about treatment and care. After extensively testing and validating the platforms, we were impressed by the speed, accuracy and cost savings conferred. Initially, we will apply the technology to a number of clinical cases where rapid turnaround is especially critical, and ultimately envisage the solution will be widely used as we scale our efforts."

Added Pieter van Rooyen, Ph.D., Chief Executive Officer of Edico Genome: "As genomics marches towards the clinic, we recognize clinicians and researchers need easy to use, all-in-one solutions that enable genomic data to be analysed and shared quickly, easily, accurately and cost effectively. Congenica has first-hand perspective of the needs of the clinical genomics community from its extensive work with the NHS, including the Genomics England initiative, and through this new collaboration we're able to create an all-in-one, easy-to-use offering that significantly accelerates the ability of hospitals and clinical labs to move from the sequencing of a sample to a clinical diagnosis."

About Congenica

Rapid, accurate and scalable diagnosis of patients with inherited genetic diseases helps accelerate access to the best clinical treatments and prevention strategies. Congenica, a global clinical genetics software company, created Sapientia that offers Clinical Scientists, Hospitals and Clinical Labs an all in one software platform to enable scalable, accurate, fast and flexible genetic diagnostic services. Congenica is a global company, headquartered in Cambridge UK and founded by pioneering researchers from the Sanger Institute.

Clinicians and scientists are using Sapientia, a cloud-based integrated software platform to analyze and interpret genetic data linked to patients' phenotypes. The software is designed to support clinical interpretation workflows and generate professional diagnostic reports. Sapientia handles the main data inputs including BAM, VCF and FASTQ files in many upload formats and the added flexibility to Integrate and manage customer legacy data to enhance diagnostic capabilities.

Find out more about Congenica at http://www.congenica.com or follow @Congenica.

About Sapientia

Sapientia facilitates analysis of genetic data to produce a comprehensive diagnostic report that can be linked to patients' symptoms, supporting clinical decision-making about rare genetic disease. The platform is based on pioneering research from the UK Wellcome Trust Sanger Institute, NHS clinicians and regional genetic testing laboratories, and its underlying technology has been validated by leading independent institutes and clinicians, including Genomics England Ltd.

About Edico Genome

The use of next-generation sequencing is growing at an unprecedented pace, creating a need for easy to implement infrastructure that enables rapid, accurate and cost-effective processing and storage of this big data. Edico Genome has created a patented, end-to-end platform solution for analysis of next-generation sequencing data, DRAGEN, which speeds whole genome data analysis from hours to minutes while maintaining high accuracy and reducing costs. Top clinicians and researchers are utilizing the platform to achieve faster diagnoses for critically ill newborns, cancer patients and expecting parents waiting on prenatal tests, and faster results for scientists and drug developers.

For more information, visit http://www.EdicoGenome.com or follow @EdicoGenome.

About DRAGEN

The DRAGEN platform features optimized algorithms for mapping, alignment, sorting, variant calling and more. Multiple end-to-end, clinical-grade pipelines are available from Edico, including genome/exome, cancer, transcriptome/RNA-seq, structural variant, copy number variant, epigenome/methyl-seq, metagenome/microbiome, joint genotyping and third-party pipelines such as GATK 3.6. The platform is flexible and allows for customization of algorithms and existing pipelines. Best-in-class solutions for onsite, cloud or hybrid cloud analysis have been created through partnerships with top technology companies, includingIntel,IBM,Dell EMC, andAmazon Web Services.

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/congenica-and-edico-genome-partner-to-speed-analysis-from-dna-to-diagnosis-for-inherited-diseases-300442461.html

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http://www.edicogenome.com

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Congenica and Edico Genome Partner to Speed Analysis from 'DNA ... - PR Newswire (press release)

April 20, 2017

Twenty years ago, the protein complex cohesin was first described by researchers at the IMP. They found that its shape strikingly corresponds to its function: when a cell divides, the ring-shaped structure of cohesin keeps sister-chromatids tied together until they are ready to separate.

Apart from this important role during cell-divison, other crucial functions of cohesin have been discovered since - at the IMP and elsewhere. One of them is to help fold the DNA, which amounts to about two meters per nucleus, into a compact size by way of creating loops. "We think that the cohesin-ring clamps onto the DNA-strand to hold the loops in place", says IMP-director Jan-Michael Peters whose team worked on the project.

The chromatin-loops are not folded at random. Their exact shape and position play an important role in gene regulation, as they bring otherwise distant areas into close contact. "For a long time, scientists were mystified by how regulatory elements the enhancers are able to activate distant genes. Now we think we know the trick: precisely folded loops allow enhancers to come very close to the genes they need to regulate", says Peters. Research results point to cohesin as mediator of this process. Jan-Michael Peters and his team have already shown that the cohesin complex accumulates in areas where loops are formed.

Several scientists recently proposed a so-called "loop-extrusion mechanism" for the folding of chromatin. According to this hypothesis, cohesin is loaded onto DNA at a random site. The DNA strain is then fed through the ring-shaped complex until it encounters a molecular barrier. This element, a DNA-binding protein named CTCF, acts much like a knot tied in a rope and stops the extrusion-process at the correct position. Defined genome-sequences that were previously located far apart are now next to each other and can interact to regulate gene expression.

In Nature online this week, IMP-researchers publish data that support the existence of such a mechanism. First author Georg Busslinger, a PhD-student in Jan-Michael Peters' team, showed in mouse cells that cohesin is indeed translocated on DNA over long distances and that the movement depends on transcription, suggesting that this may serve as a 'motor'.

"The loop extrusion hypothesis has opened up a whole new research area in cell biology and we will probably see many more papers published on this topic in the future", comments Jan-Michael Peters. Understanding cohesin-function is also relevant from a medical perspective since a number of disorders, including certain cancers, are associated with malfunctions of the protein-complex.

Explore further: Regulator of chromosome structure crucial to healthy brain function and nerve development

More information: Georg A. Busslinger et al. Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl, Nature (2017). DOI: 10.1038/nature22063

In the nucleus of eukaryotic cells, DNA is packaged with histone proteins into complexes known as chromatin, which are further compacted into chromosomes during cell division. Abnormalities in the structure of chromosomes ...

Researchers at the IMP Vienna discovered that cohesin stabilizes DNA. Jan-Michael Peters and his team at the Research Institute of Molecular Pathology (IMP) found that the structure of Chromosomes is supported by a kind of ...

The cohesin molecule ensures the proper distribution of DNA during cell division. Scientists at the Research Institute of Molecular Pathology (IMP) in Vienna can now prove the concept of its carabiner-like function by visualizing ...

Ten years ago, researchers at the IMP - a basic research institute in Vienna - discovered a fundamental and amazingly plausible mechanism of cell division. They identified a protein complex, which, as a ring-shaped molecule, ...

Protein factors are responsible for organizing chromosomes inside the nucleus in three dimensions (3D), forming a shape like a gift bow, with proteins aggregating as the central 'knot' holding the ribbon-like loops of DNA ...

Within almost every human cell is a nucleus six microns in diameterabout one 300th of a human hair's widththat is filled with roughly three meters of DNA. As the instructions for all cell processes, the DNA must be ...

Scientists at the Centre for Genomic Regulation (CRG) in Barcelona and the Josep Carreras Leukaemia Research Institute and The Institute for Health Science Research Germans Trias i Pujol (IGTP) in Badalona, Spain, have discovered ...

Nematodes are microscopic worms that fall into an often ignored corner of the animal kingdom. While many of them are parasitic, meaning they live inside other organisms, they also help control diseases in humans and kill ...

Gut microbes play wide-ranging roles in health and disease, but there has been a lack of tools to probe the relationship between microbial activity and host physiology. Two independent studies in mice published April 20 in ...

The tobacco hawkmoth Manduca sexta is an important pollinator of the wild tobacco species Nicotiana attenuata; yet hungry larvae hatch from the eggs these moths lay on the leaves. An interdisciplinary team of scientists at ...

Proper nutrition can unleash amazing powers, moms have always assured us, frequently citing Popeye the Sailor Man as evidence. Now, two University of Colorado Boulder scientists have confirmed just how potent some nutrients ...

Researchers have uncovered molecular details of how pathogenic bacteria fight back against the human immune response to infection.

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Looping the genomehow cohesin does the trick - Phys.Org

THE VENEMA CHAPTERS

Chapter Two provides us with a useful analogy about the development over time incrementally of a language (e.g. the word treuth becomes truthe and then truth) and the development of a human genetic code. While languages can change rather quickly, biological speciation and change takes place over thousands of years and herein lies another problem: 1) no one is around that long to observe the change, indeed whole civilizations rise and fall in the time it takes for even an incremental change of that sort; 2) no one WAS around when this process began, in fact Venema is clear enough that even the fossil record only goes back 200,000 years max, but evolutionary theory requires a much much longer timeline to account for all the genetic permutations and combinations. Thus, we are talking about extrapolation back in time based on modern science, when the actual empirical observation of the change has not taken place over the time period required. 3) the assumption is that things are operating now, as they always have done according to the modern theories of evolution and natural development. But alas, we have no time machine to go back and check the math and the genetics from long, long ago. Again, no room is allowed for God to tinker with the process along the way, he simply set it in motion and is observing. But what about that language analogy Venema wants to use?

Evolutionary theory can be guilty of the etymological fallacy, assuming that notable similarities between things must be caused by a shared common ancestry. Since Venema uses the analogy with language, I shall do the same at this point. Lets take the English word bare, which in Old English was baer, very close, and having exactly the same letters as bear. Ah ha, you say, these two words must share a common ancestor! Not a bit of it. Bare seems to come from the Dutch baar, and ultimately from the proto-Germanic bazaz. By contrast bear comes from the old word for brown or the brown one; beron in proto-Germanic or in old Norse bjorn, like the current Scandanvian name.

Genetics has done a wonderful job of showing lots of similarities in the letters etc. of the genetic code. Its when they try to explain the similarities that the train comes off the tracks. There are other possible, legitimate explanations for similarities other than they must share a common ancestor.

Imagine two builders who intend to build two different buildings, serving different purposes. But the construction materials are exactly the samecinder blocks, boards, shingles, electrical wires, plumbing and so on. One building is an exercise gym, the other building is an apartment complex. One building is single story, the other is a high rise. Would anyone actually want to say that Building B came from or is an evolved form of Building A, just because they shared lots of common materials or building blocks? No. Similarity of make-up is no proof of derivation.

DNA, genes, genomes, tell us a lot about the building blocks that go into the making of all sorts of creatures on earth. Detailed genetic study can show possible connections based on similar genetic patterns and codes. But we all know the problem of coming up with a very good hypothesis, or even a theory (a hypothesis that provides the best explanation of a particular sort for the known facts on the ground), that does not take into account all the evidence. You can argue consistently and coherently with and within a certain circle of evidence, and be incorrect, because you have not taken into account (or in some cases even deliberately eliminated) some of the evidence.

Continued here:
Adam and the Genome Part Four - Patheos (blog)

Genomics is an interdisciplinary field of science focusing on genomes.[1] A genome is a complete set of DNA within a single cell of an organism, and as such genomics is a branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes. Genomics aims at the collective characterization and quantification of genes, which direct the production of proteins with the assistance of enzymes and messenger molecules. Proteins in turn make up body structures like organs and tissues as well as control chemical reactions and carry signals between cells. If a cell's DNA is mutated, an abnormal protein may be produced, which can disrupt the body's usual processes and in some cases lead to diseases such as cancer. In contrast to genetics, which refers to the study of genes and their roles in inheritance, genomics is the study of genes, their functions, and related techniques, such as applications of recombinant DNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes.[2][3] Advances in genomics have triggered a revolution in discovery-based research to understand even the most complex biological systems such as the brain.[4] The field includes efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping. The field also includes studies of intragenomic phenomena such as heterosis, epistasis, pleiotropy and other interactions between loci and alleles within the genome.[5] Research carried out into single genes does not generally fall into the definition of genomics unless the aim of this genetic, pathway, and functional information analysis is to elucidate its effect on, place in, and response to the entire genomes networks.[6][not specific enough to verify]

From the Greek [7]gen, "gene" (gamma, epsilon, nu, epsilon) meaning "become, create, creation, birth", and subsequent variants: genealogy, genesis, genetics, genic, genomere, genotype, genus etc. While the word genome (from the German Genom, attributed to Hans Winkler) was in use in English as early as 1926,[8] the term genomics was coined by Tom Roderick, a geneticist at the Jackson Laboratory (Bar Harbor, Maine), over beer at a meeting held in Maryland on the mapping of the human genome in 1986.[9]

Following Rosalind Franklin's confirmation of the helical structure of DNA, James D. Watson and Francis Crick's publication of the structure of DNA in 1953 and Fred Sanger's publication of the Amino acid sequence of insulin in 1955, nucleic acid sequencing became a major target of early molecular biologists.[10] In 1964, Robert W. Holley and colleagues published the first nucleic acid sequence ever determined, the ribonucleotide sequence of alanine transfer RNA.[11][12] Extending this work, Marshall Nirenberg and Philip Leder revealed the triplet nature of the genetic code and were able to determine the sequences of 54 out of 64 codons in their experiments.[13] In 1972, Walter Fiers and his team at the Laboratory of Molecular Biology of the University of Ghent (Ghent, Belgium) were the first to determine the sequence of a gene: the gene for Bacteriophage MS2 coat protein.[14] Fiers' group expanded on their MS2 coat protein work, determining the complete nucleotide-sequence of bacteriophage MS2-RNA (whose genome encodes just four genes in 3569 base pairs [bp]) and Simian virus 40 in 1976 and 1978, respectively.[15][16]

In addition to his seminal work on the amino acid sequence of insulin, Frederick Sanger and his colleagues played a key role in the development of DNA sequencing techniques that enabled the establishment of comprehensive genome sequencing projects.[5] In 1975, he and Alan Coulson published a sequencing procedure using DNA polymerase with radiolabelled nucleotides that he called the Plus and Minus technique.[17][18] This involved two closely related methods that generated short oligonucleotides with defined 3' termini. These could be fractionated by electrophoresis on a polyacrylamide gel (called polyacrylamide gel electrophoresis) and visualised using autoradiography. The procedure could sequence up to 80 nucleotides in one go and was a big improvement, but was still very laborious. Nevertheless, in 1977 his group was able to sequence most of the 5,386 nucleotides of the single-stranded bacteriophage X174, completing the first fully sequenced DNA-based genome.[19] The refinement of the Plus and Minus method resulted in the chain-termination, or Sanger method (see below), which formed the basis of the techniques of DNA sequencing, genome mapping, data storage, and bioinformatic analysis most widely used in the following quarter-century of research.[20][21] In the same year Walter Gilbert and Allan Maxam of Harvard University independently developed the Maxam-Gilbert method (also known as the chemical method) of DNA sequencing, involving the preferential cleavage of DNA at known bases, a less efficient method.[22][23] For their groundbreaking work in the sequencing of nucleic acids, Gilbert and Sanger shared half the 1980 Nobel Prize in chemistry with Paul Berg (recombinant DNA).

The advent of these technologies resulted in a rapid intensification in the scope and speed of completion of genome sequencing projects. The first complete genome sequence of an eukaryotic organelle, the human mitochondrion (16,568 bp, about 16.6 kb [kilobase]), was reported in 1981,[24] and the first chloroplast genomes followed in 1986.[25][26] In 1992, the first eukaryotic chromosome, chromosome III of brewer's yeast Saccharomyces cerevisiae (315 kb) was sequenced.[27] The first free-living organism to be sequenced was that of Haemophilus influenzae (1.8 Mb [megabase]) in 1995.[28] The following year a consortium of researchers from laboratories across North America, Europe, and Japan announced the completion of the first complete genome sequence of a eukaryote, S. cerevisiae (12.1 Mb), and since then genomes have continued being sequenced at an exponentially growing pace.[29] As of October 2011[update], the complete sequences are available for: 2,719 viruses, 1,115 archaea and bacteria, and 36 eukaryotes, of which about half are fungi.[30][31]

Most of the microorganisms whose genomes have been completely sequenced are problematic pathogens, such as Haemophilus influenzae, which has resulted in a pronounced bias in their phylogenetic distribution compared to the breadth of microbial diversity.[32][33] Of the other sequenced species, most were chosen because they were well-studied model organisms or promised to become good models. Yeast (Saccharomyces cerevisiae) has long been an important model organism for the eukaryotic cell, while the fruit fly Drosophila melanogaster has been a very important tool (notably in early pre-molecular genetics). The worm Caenorhabditis elegans is an often used simple model for multicellular organisms. The zebrafish Brachydanio rerio is used for many developmental studies on the molecular level, and the flower Arabidopsis thaliana is a model organism for flowering plants. The Japanese pufferfish (Takifugu rubripes) and the spotted green pufferfish (Tetraodon nigroviridis) are interesting because of their small and compact genomes, which contain very little noncoding DNA compared to most species.[34][35] The mammals dog (Canis familiaris),[36] brown rat (Rattus norvegicus), mouse (Mus musculus), and chimpanzee (Pan troglodytes) are all important model animals in medical research.[23]

A rough draft of the human genome was completed by the Human Genome Project in early 2001, creating much fanfare.[37] This project, completed in 2003, sequenced the entire genome for one specific person, and by 2007 this sequence was declared "finished" (less than one error in 20,000 bases and all chromosomes assembled).[37] In the years since then, the genomes of many other individuals have been sequenced, partly under the auspices of the 1000 Genomes Project, which announced the sequencing of 1,092 genomes in October 2012.[38] Completion of this project was made possible by the development of dramatically more efficient sequencing technologies and required the commitment of significant bioinformatics resources from a large international collaboration.[39] The continued analysis of human genomic data has profound political and social repercussions for human societies.[40]

The English-language neologism omics informally refers to a field of study in biology ending in -omics, such as genomics, proteomics or metabolomics. The related suffix -ome is used to address the objects of study of such fields, such as the genome, proteome or metabolome respectively. The suffix -ome as used in molecular biology refers to a totality of some sort; similarly omics has come to refer generally to the study of large, comprehensive biological data sets. While the growth in the use of the term has led some scientists (Jonathan Eisen, among others[41]) to claim that it has been oversold,[42] it reflects the change in orientation towards the quantitative analysis of complete or near-complete assortment of all the constituents of a system.[43] In the study of symbioses, for example, researchers which were once limited to the study of a single gene product can now simultaneously compare the total complement of several types of biological molecules.[44][45]

After an organism has been selected, genome projects involve three components: the sequencing of DNA, the assembly of that sequence to create a representation of the original chromosome, and the annotation and analysis of that representation.[5]

Historically, sequencing was done in sequencing centers, centralized facilities (ranging from large independent institutions such as Joint Genome Institute which sequence dozens of terabases a year, to local molecular biology core facilities) which contain research laboratories with the costly instrumentation and technical support necessary. As sequencing technology continues to improve, however, a new generation of effective fast turnaround benchtop sequencers has come within reach of the average academic laboratory.[46][47] On the whole, genome sequencing approaches fall into two broad categories, shotgun and high-throughput (aka next-generation) sequencing.[5]

Shotgun sequencing (Sanger sequencing is used interchangeably) is a sequencing method designed for analysis of DNA sequences longer than 1000 base pairs, up to and including entire chromosomes.[48] It is named by analogy with the rapidly expanding, quasi-random firing pattern of a shotgun. Since the chain termination method of DNA sequencing can only be used for fairly short strands (100 to 1000 base pairs), longer DNA sequences must be broken into random small segments which are then sequenced to obtain reads. Multiple overlapping reads for the target DNA are obtained by performing several rounds of this fragmentation and sequencing. Computer programs then use the overlapping ends of different reads to assemble them into a continuous sequence.[48][49] Shotgun sequencing is a random sampling process, requiring over-sampling to ensure a given nucleotide is represented in the reconstructed sequence; the average number of reads by which a genome is over-sampled is referred to as coverage.[50]

For much of its history, the technology underlying shotgun sequencing was the classical chain-termination method, which is based on the selective incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication.[19][51] Developed by Frederick Sanger and colleagues in 1977, it was the most widely used sequencing method for approximately 25 years. More recently, Sanger sequencing has been supplanted by "Next-Gen" sequencing methods, especially for large-scale, automated genome analyses. However, the Sanger method remains in wide use in 2013, primarily for smaller-scale projects and for obtaining especially long contiguous DNA sequence reads (>500 nucleotides).[52] Chain-termination methods require a single-stranded DNA template, a DNA primer, a DNA polymerase, normal deoxynucleosidetriphosphates (dNTPs), and modified nucleotides (dideoxyNTPs) that terminate DNA strand elongation. These chain-terminating nucleotides lack a 3'-OH group required for the formation of a phosphodiester bond between two nucleotides, causing DNA polymerase to cease extension of DNA when a ddNTP is incorporated. The ddNTPs may be radioactively or fluorescently labelled for detection in automated sequencing machines.[5] Typically, these automated DNA-sequencing instruments (DNA sequencers) can sequence up to 96 DNA samples in a single batch (run) in up to 48 runs a day.[53]

The high demand for low-cost sequencing has driven the development of high-throughput sequencing (or next-generation sequencing [NGS]) technologies that parallelize the sequencing process, producing thousands or millions of sequences at once.[54][55] High-throughput sequencing technologies are intended to lower the cost of DNA sequencing beyond what is possible with standard dye-terminator methods. In ultra-high-throughput sequencing as many as 500,000 sequencing-by-synthesis operations may be run in parallel.[56][57]

Solexa, now part of Illumina, developed a sequencing method based on reversible dye-terminators technology acquired from Manteia Predictive Medicine in 2004. This technology had been invented and developed in late 1996 at Glaxo-Welcome's Geneva Biomedical Research Institute (GBRI), by Dr. Pascal Mayer and Dr Laurent Farinelli.[58] In this method, DNA molecules and primers are first attached on a slide and amplified with polymerase so that local clonal colonies, initially coined "DNA colonies", are formed. To determine the sequence, four types of reversible terminator bases (RT-bases) are added and non-incorporated nucleotides are washed away. Unlike pyrosequencing, the DNA chains are extended one nucleotide at a time and image acquisition can be performed at a delayed moment, allowing for very large arrays of DNA colonies to be captured by sequential images taken from a single camera.

Decoupling the enzymatic reaction and the image capture allows for optimal throughput and theoretically unlimited sequencing capacity. With an optimal configuration, the ultimately reachable instrument throughput is thus dictated solely by the analogic-to-digital conversion rate of the camera, multiplied by the number of cameras and divided by the number of pixels per DNA colony required for visualizing them optimally (approximately 10 pixels/colony). In 2012, with cameras operating at more than 10MHz A/D conversion rates and available optics, fluidics and enzymatics, throughput can be multiples of 1 million nucleotides/second, corresponding roughly to 1 human genome equivalent at 1x coverage per hour per instrument, and 1 human genome re-sequenced (at approx. 30x) per day per instrument (equipped with a single camera). The camera takes images of the fluorescently labeled nucleotides, then the dye along with the terminal 3' blocker is chemically removed from the DNA, allowing the next cycle.[59]

Ion Torrent Systems Inc. developed a sequencing approach based on standard DNA replication chemistry. This technology measures the release of a hydrogen ion each time a base is incorporated. A microwell containing template DNA is flooded with a single nucleotide, if the nucleotide is complementary to the template strand it will be incorporated and a hydrogen ion will be released. This release triggers an ISFET ion sensor. If a homopolymer is present in the template sequence multiple nucleotides will be incorporated in a single flood cycle, and the detected electrical signal will be proportionally higher.[60]

Overlapping reads form contigs; contigs and gaps of known length form scaffolds.

Paired end reads of next generation sequencing data mapped to a reference genome.

Multiple, fragmented sequence reads must be assembled together on the basis of their overlapping areas.

Sequence assembly refers to aligning and merging fragments of a much longer DNA sequence in order to reconstruct the original sequence.[5] This is needed as current DNA sequencing technology cannot read whole genomes as a continuous sequence, but rather reads small pieces of between 20 and 1000 bases, depending on the technology used. Typically the short fragments, called reads, result from shotgun sequencing genomic DNA, or gene transcripts (ESTs).[5]

Assembly can be broadly categorized into two approaches: de novo assembly, for genomes which are not similar to any sequenced in the past, and comparative assembly, which uses the existing sequence of a closely related organism as a reference during assembly.[50] Relative to comparative assembly, de novo assembly is computationally difficult (NP-hard), making it less favorable for short-read NGS technologies.

Finished genomes are defined as having a single contiguous sequence with no ambiguities representing each replicon.[61]

The DNA sequence assembly alone is of little value without additional analysis.[5]Genome annotation is the process of attaching biological information to sequences, and consists of three main steps:[62]

Automatic annotation tools try to perform these steps in silico, as opposed to manual annotation (a.k.a. curation) which involves human expertise and potential experimental verification.[63] Ideally, these approaches co-exist and complement each other in the same annotation pipeline (also see below).

Traditionally, the basic level of annotation is using BLAST for finding similarities, and then annotating genomes based on homologues.[5] More recently, additional information is added to the annotation platform. The additional information allows manual annotators to deconvolute discrepancies between genes that are given the same annotation. Some databases use genome context information, similarity scores, experimental data, and integrations of other resources to provide genome annotations through their Subsystems approach. Other databases (e.g. Ensembl) rely on both curated data sources as well as a range of software tools in their automated genome annotation pipeline.[64]Structural annotation consists of the identification of genomic elements, primarily ORFs and their localisation, or gene structure. Functional annotation consists of attaching biological information to genomic elements.

The need for reproducibility and efficient management of the large amount of data associated with genome projects mean that computational pipelines have important applications in genomics.[65]

Functional genomics is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects (such as genome sequencing projects) to describe gene (and protein) functions and interactions. Functional genomics focuses on the dynamic aspects such as gene transcription, translation, and proteinprotein interactions, as opposed to the static aspects of the genomic information such as DNA sequence or structures. Functional genomics attempts to answer questions about the function of DNA at the levels of genes, RNA transcripts, and protein products. A key characteristic of functional genomics studies is their genome-wide approach to these questions, generally involving high-throughput methods rather than a more traditional gene-by-gene approach.

A major branch of genomics is still concerned with sequencing the genomes of various organisms, but the knowledge of full genomes has created the possibility for the field of functional genomics, mainly concerned with patterns of gene expression during various conditions. The most important tools here are microarrays and bioinformatics.

Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome.[66][67] This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling approaches. The principal difference between structural genomics and traditional structural prediction is that structural genomics attempts to determine the structure of every protein encoded by the genome, rather than focusing on one particular protein. With full-genome sequences available, structure prediction can be done more quickly through a combination of experimental and modeling approaches, especially because the availability of large numbers of sequenced genomes and previously solved protein structures allow scientists to model protein structure on the structures of previously solved homologs. Structural genomics involves taking a large number of approaches to structure determination, including experimental methods using genomic sequences or modeling-based approaches based on sequence or structural homology to a protein of known structure or based on chemical and physical principles for a protein with no homology to any known structure. As opposed to traditional structural biology, the determination of a protein structure through a structural genomics effort often (but not always) comes before anything is known regarding the protein function. This raises new challenges in structural bioinformatics, i.e. determining protein function from its 3D structure.[68]

Epigenomics is the study of the complete set of epigenetic modifications on the genetic material of a cell, known as the epigenome.[69] Epigenetic modifications are reversible modifications on a cells DNA or histones that affect gene expression without altering the DNA sequence (Russell 2010 p.475). Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Epigenetic modifications play an important role in gene expression and regulation, and are involved in numerous cellular processes such as in differentiation/development and tumorigenesis.[69] The study of epigenetics on a global level has been made possible only recently through the adaptation of genomic high-throughput assays.[70]

Metagenomics is the study of metagenomes, genetic material recovered directly from environmental samples. The broad field may also be referred to as environmental genomics, ecogenomics or community genomics. While traditional microbiology and microbial genome sequencing rely upon cultivated clonal cultures, early environmental gene sequencing cloned specific genes (often the 16S rRNA gene) to produce a profile of diversity in a natural sample. Such work revealed that the vast majority of microbial biodiversity had been missed by cultivation-based methods.[71] Recent studies use "shotgun" Sanger sequencing or massively parallel pyrosequencing to get largely unbiased samples of all genes from all the members of the sampled communities.[72] Because of its power to reveal the previously hidden diversity of microscopic life, metagenomics offers a powerful lens for viewing the microbial world that has the potential to revolutionize understanding of the entire living world.[73][74]

Bacteriophages have played and continue to play a key role in bacterial genetics and molecular biology. Historically, they were used to define gene structure and gene regulation. Also the first genome to be sequenced was a bacteriophage. However, bacteriophage research did not lead the genomics revolution, which is clearly dominated by bacterial genomics. Only very recently has the study of bacteriophage genomes become prominent, thereby enabling researchers to understand the mechanisms underlying phage evolution. Bacteriophage genome sequences can be obtained through direct sequencing of isolated bacteriophages, but can also be derived as part of microbial genomes. Analysis of bacterial genomes has shown that a substantial amount of microbial DNA consists of prophage sequences and prophage-like elements.[75] A detailed database mining of these sequences offers insights into the role of prophages in shaping the bacterial genome.[76][77]

At present there are 24 cyanobacteria for which a total genome sequence is available. 15 of these cyanobacteria come from the marine environment. These are six Prochlorococcus strains, seven marine Synechococcus strains, Trichodesmium erythraeum IMS101 and Crocosphaera watsonii WH8501. Several studies have demonstrated how these sequences could be used very successfully to infer important ecological and physiological characteristics of marine cyanobacteria. However, there are many more genome projects currently in progress, amongst those there are further Prochlorococcus and marine Synechococcus isolates, Acaryochloris and Prochloron, the N2-fixing filamentous cyanobacteria Nodularia spumigena, Lyngbya aestuarii and Lyngbya majuscula, as well as bacteriophages infecting marine cyanobaceria. Thus, the growing body of genome information can also be tapped in a more general way to address global problems by applying a comparative approach. Some new and exciting examples of progress in this field are the identification of genes for regulatory RNAs, insights into the evolutionary origin of photosynthesis, or estimation of the contribution of horizontal gene transfer to the genomes that have been analyzed.[78]

Genomics has provided applications in many fields, including medicine, biotechnology, anthropology and other social sciences.[40]

Next-generation genomic technologies allow clinicians and biomedical researchers to drastically increase the amount of genomic data collected on large study populations.[79] When combined with new informatics approaches that integrate many kinds of data with genomic data in disease research, this allows researchers to better understand the genetic bases of drug response and disease.[80][81]

The growth of genomic knowledge has enabled increasingly sophisticated applications of synthetic biology.[82] In 2010 researchers at the J. Craig Venter Institute announced the creation of a partially synthetic species of bacterium, Mycoplasma laboratorium, derived from the genome of Mycoplasma genitalium.[83]

Conservationists can use the information gathered by genomic sequencing in order to better evaluate genetic factors key to species conservation, such as the genetic diversity of a population or whether an individual is heterozygous for a recessive inherited genetic disorder.[84] By using genomic data to evaluate the effects of evolutionary processes and to detect patterns in variation throughout a given population, conservationists can formulate plans to aid a given species without as many variables left unknown as those unaddressed by standard genetic approaches.[85]

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Genomics - Wikipedia