DNA

Novel faultless DNA construction method from imperfect oligonucleotides

Attila Csordas — Wed, 14 May 2008 20:00:52 -0700

Description

A novel recursive DNA construction procedure was reported by scientists from the Weizmann Institute of Science, Rehovot, Israel constructing couple of kilobases long DNA molecules. They are claiming that their method "surpasses existing methods for de novo DNA synthesis in speed, precision, amenability to automation, ease of combining synthetic and natural DNA fragments, and ability to construct designer DNA libraries. It thus provides a novel and robust foundation for the design and construction of synthetic biological molecules and organisms."

From the abstract:

"Making faultless complex objects from potentially faulty building blocks is a fundamental challenge in computer engineering, nanotechnology and synthetic biology. Here, we show for the first time how recursion can be used to address this challenge and demonstrate a recursive procedure that constructs error-free DNA molecules and their libraries from error-prone oligonucleotides. Divide and Conquer (D&C), the quintessential recursive problem-solving technique, is applied in silico to divide the target DNA sequence into overlapping oligonucleotides short enough to be synthesized directly, albeit with errors; error-prone oligonucleotides are recursively combined in vitro, forming error-prone DNA molecules; error-free fragments of these molecules are then identified, extracted and used as new, typically longer and more accurate, inputs to another iteration of the recursive construction procedure; the entire process repeats until an error-free target molecule is formed."

Biomedical Sciences and Biotechnology

Source

Gregory Linshiz, Tuval Ben Yehezkel, Shai Kaplan, Ilan Gronau, Sivan Ravid, Rivka Adar & Ehud Shapiro: Recursive construction of perfect DNA molecules from imperfect oligonucleotides
http://www.nature.com/msb/journal/v4/n1/full/msb200826.html
Molecular Systems Biology 4 Article number: 191 doi:10.1038/msb.2008.26
Published online: 6 May 2008
Citation: Molecular Systems Biology 4:191

Biologists Enlist Online Gamers

Sean Ness — Fri, 09 May 2008 18:10:09 -0700

Description

Proteins are the workhorses of biology. Among their many functions, proteins speed chemical reactions, enable blood cells to recognize intruding viruses, and copy DNA. The potential payoffs of making proteins that don't exist in nature, such as those needed for HIV vaccines or as catalysts for more-efficient biofuel production, are huge. But making proteins to meet a specific need can be difficult.

Now a leading protein researcher has teamed up with computer scientists to create an online game for developing useful protein structures. David Baker, a leading protein scientist at the University of Washington, says that players will help his lab design new vaccines and make enzymes for repairing DNA in diseased tissues.

For years, biochemists have reengineered naturally occurring proteins by growing them in viruses and single-celled organisms in a process called directed evolution. But researchers need to start with a preexisting protein, which makes it difficult to develop proteins with totally new functions. In a major step forward, Baker recently demonstrated the first algorithm for building novel, functioning enzymes from scratch. But while proteins built from the ground up may have chemical properties unmatched by anything in nature, they aren't particularly efficient.

Biomedical Sciences and Biotechnology

Source

http://www.technologyreview.com/Biotech/20738/?a=f

By 2015, babies might have their entire DNA read at birth

Sean Ness — Fri, 25 Apr 2008 09:19:04 -0700

Description

By 2015, babies might have their entire DNA read at birth, as costs of sequencing plunge. Charles Arthur looks at the implications for individuals and society.

Had one of his parents been slightly less fortunate in their choice of a mate, James Watson might not have helped discover the structure of DNA in 1953. Instead, he would have been born deaf, and then lost his sight as he became a teenager. Equally, as he is, had he been less fortunate in the genetic lottery when he chose his wife, either of their sons might have had the same fate.

This is because Watson's complete DNA - his genome - contains a single gene for Usher's syndrome, an inherited disorder which affects hearing and sight. Watson's must have come from one of his parents. Usher's is a "recessive" disease - you need two copies of the gene to be affected. About five people per 100,000 carry the gene, so Watson's chances of being disabled weren't large. But they were real.

Revealing the risk

We know this because the analysis of his genome was made public last week, in a groundbreaking paper in the science journal Nature that also revealed that he carries genes that may increase his risk of cancer, including one linked to breast cancer. While the sequencing of genomes for research has become almost routine - so far the genomes of dozens of species have been sequenced - Watson's was notable for how quickly and cheaply it was done.

The first full human genome sequencing, completed in 2003, took 13 years and cost $437m (£220m). Watson's sequencing, carried out by a company called 454 Life Sciences, took only two months and cost about $1m. Other companies, such as Illumina and Applied Biosystems, are relentlessly pushing the cost down.

Reading the 3bn "base pairs" in human DNA - akin to letters, encoding a total of between 20,000 and 30,000 genes that are the "words" of genetics - is getting faster as companies find quicker ways to "read" entire stretches of DNA at a time, like reading a sentence in chunks rather than letter by letter. 454's can read up to 450 bases at a time; Pacific BioSciences, one of many rivals, more than a thousand.

The cost of sequencing an individual genome is thus falling exponentially - just as the cost of hard disk space or transistors on a chip did when computing took off. Plotting the numbers on a graph suggests that by 2012 it will take a few hours and cost less than $100. A few years after that it will cost perhaps $10.

That's when you should expect an explosion in personal sequencing. Jason Bobe, the director of community for the Personal Genome Project, based at Harvard Medical School, writes the Personal Genome blog and reckons that by 2015, 50 million people will have had their own DNA sequenced. He says: "My rationale is simply to assume that the trend line for the personal sequencing market might look a lot like the one experienced in the personal computer market" - which grew from a few thousand units sold in 1975 to 50m in 1995. "If the personal genome sequencing market follows suit, we might say that 2007 for personal genome sequences was like 1979 for PCs, and we've just turned the corner into 1980 where units sold remains below 1m, but growth is noticeable."

Who benefits?

Cheap, fast genome sequencing could upend how we think of disease and identity. If it's fast and cheap enough, would benefits claimants be asked to provide a DNA swab from their cheek? Would the same swab be your passport? Might police at a crime scene simply scan for DNA?

The first, most obvious, use is foetal testing. Would a future James Watson and would-be spouse compare genomes? If both had single genes for Usher's syndrome, would they have children anyway, given the one-in-four chance that their child might have the full-blown syndrome? Would abortions be allowed on the basis that a child would have a disabling - but by no means life-threatening - genetic disease? The impending arrival of everyone's genome only makes this more urgent.

Watson himself, on seeing the presence of his breast cancer gene, said he would have acted on the knowledge had he had daughters: "I would tell them to immediately check if they had [that mutation]." But he also chose to withhold parts of the sequence relating to the APOE gene - associated with a higher risk of Alzheimer's disease - because he doesn't want to know if he has a genetic disposition to it.

His nuanced approach will be food for thought for the House of Lords select committee on science, which this week opens an inquiry into "genomic medicine".

Mark Jobling, professor of genetics at the University of Leicester, notes that: "The problem is that many common genetic diseases are complex. It isn't a single base change. More complex diseases like schizophrenia and Alzheimer's won't be predictable."

The idea of DNA profiling to collect benefits isn't new. It was suggested by the Labour MP Frank Field, then in opposition, as long ago as July 1996, "to safeguard the National Insurance system" - though he insisted that this was not "the introduction of an ID card".

He added: "A DNA test should be taken at birth along with all the other tests which are now merely a routine." The suggestions caused outrage at the time; but routinely sequencing a baby's genome at birth will be possible in a decade.

Precisely that suggestion - of routine genomic sequencing of newborns - was suggested in a 2003 policy paper on the NHS, points out Dr Helen Wallace, director of Genewatch UK. "It was criticised on cost grounds," she notes, "but more particularly because most of that information [about an individual's genome] was likely to be misleading. OK, you can tell where someone has recessive genes that might lead to a known genetic illness, but the claims being made now by some of the companies offering sequencing are leading to concern and fear of disease."

Wallace suggests that they are distractions. "You share your environment and lifestyle with your family and for most of us this will be more important than our genes," she says. "Gene tests won't help to tackle major health problems such as bad diets, poverty, smoking and pollution." Genewatch generally opposes universal sequencing, on surveillance grounds.

What about crime scene tests? Jobling says: "The only reason for doing a full genome sequence would be for phenotype prediction, if you found DNA and didn't have a match. There have been some genetic variants already discovered that affect height; you might know eyes, hair ... you could produce an identikit predictive picture of your suspect. But in terms of individual ID, [DNA fingerprinting is] already perfectly adequate as it is."

Sequential growth

There's also the question of how far the price of testing will fall. Jobling points to one key difference between computers and DNA sequencers: computers are all-purpose machines. PCs are a mass technology, Jobling notes, "whereas it's difficult to see that there would be a case for having a DNA sequencer in every home. We've got a new sequencer here at the university and it cost £250,000, with an annnual maintenance contract of £25,000. And that's before we've switched it on."

So, he says: "How far down the cost [of sequencing] will go will be determined by the final size of the market and its applications." But if the whole population is sequenced from birth, and your DNA becomes your passport and benefit ID, that will expand the market - perhaps making it a self-fulfilling prediction. James Watson may be among the first. But many will follow.
The rapidly falling cost and time needed to map your DNA

2003
$437,000,000
13 years to map

2007
$10,000,000
4 years

2008
$100,000
4 weeks

2012
$100*
2 days

*Forecast

Source

http://www.guardian.co.uk/technology/2008/apr/24/research.politics?gusrc=rss&feed=science

Handheld DNA Detector

Bartlett Bulkley — Thu, 13 Mar 2008 14:40:12 -0700

NOTE: This content was aggregated from RSS feed. Original source is http://feeds.sciencedaily.com/~r/sciencedaily/~3/250910745/080310173246.htm

A scientists has taken a mathematical approach to a biological problem -- how to design a portable DNA detector. A mathematical simulation shows how a new type of nanoscale transistor might be coupled to a DNA sensor system.

Making a business out of personalized genomics

Attila Csordas — Thu, 22 Nov 2007 11:05:04 -0800

Description

From the 90s pharmacogenomics attempted to harness the power of genetic information by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity thereby personalising and optimising drug therapy. Large scale pharmacogenomics is still unproven so far. But ever since the completion of the Human Genome Project in 2003 there were hopes within the biotech industry that all the new and aggregated genetic information could be harnessed and commercialized. From the technological side the falling price of genotyping microarrays spurs a wave of research and in May, 2007 the genome of James Watson was sequenced followed by the published whole genome sequence of Craig Venter in September. Meanwhile the Personal Genome Project lead by George Church is recruiting volunteers to develop affordable "personal genome sequences" and a variety of user-friendly applications of such data.

But the real jump into the deep comes in November when the newly launched, Mountain View based 23andMe 23andMe is the first and web based biotech company offering personalized genome service to its customers including interpreted and probabilistic information on the health risks of the customer’s genetic profile. 23andMe opens for business, offering retail genotyping for $1,000. Other contenders include Navigenics, a startup planning to launch early next year; DNA Direct, which already offers individual gene tests online; and DeCode Genetics, which conducts original research and is developing new drugs.

According to 23andMe:

23andMe looks at nearly 600,000 SNPs scattered across the 23 pairs of chromosomes that constitute the human genetic sequence. We also look at a few thousand places on the mitochondrial DNA, an odd loop of genetic material outside the nucleus that is involved in producing energy for the cell. The technology that we use, the Illumina HumanHap 550+ BeadChip, analyzes more than 550,000 SNPs that cover the entire genome. Although this is still only a fraction of the 10 million SNPs that are estimated to be in the human genome, these 550,000 are specially selected because they provide a lot of information about other nearby SNPs. In addition, we have hand-picked more than 30,000 additional SNPs of particular interest from the scientific literature and added them to the chip. As a result, we can provide you with unique, genetic information available through no other service.

What does the process at 23andMe look like? Customer is building the order online, spit 2.5 mls of saliva into a plastic tube in the postal delivered Saliva Kit, FedEx the saliva back to Mountain View, wait a couple of weeks for an email.

Once a customer’s DNA is analyzed, the information is loaded into the secure database where it can be accessed and viewed by the customer. Says Thomas Goetz in Wired:

"There are three main sections to the Web site: Genome Labs, where users can navigate through the raw catalog of their 23 pairs of chromosomes; Gene Journals, where the company correlates your genome with current research on a dozen or so diseases and conditions, from type 2 diabetes to Crohn's disease; and Ancestry, where customers can reach back through their DNA and discover their lineage, as well as explore their relationships with ethnic groups around the world. Family members can share profiles, trace the origin of particular traits, and compare one cousin's genome to another in a fascinating display of DNA networking. In the “gene journal” section of the site, the customer can use “The 23andMe Odds Calculator”, which helps the user understand which “common health concerns are most likely to affect a person with your genetic profile.” It is absolutely vital to note that this calculation is NOT meant to serve as a medical diagnostic or medical advice – it is merely a tool to learn more about an individual’s DNA. The ability of science to predict disease based on genetics is still in its infancy, so 23andMe will continue to update the gene journal with new information and data as it becomes available."

There are other cautions too that should be addressed concerning the scientific background of 23andMe's technology. David Ewing Duncan writes:

"Scientists and ethicists warn that the understanding of most genes remains a work in progress—and, as a result, users could make life decisions based on incomplete or erroneous science. “Just because we have identified a gene doesn’t mean its function or its impact has been thoroughly understood or that having a gene has any real predictive value,” says Francis Collins, who led the international consortium that sequenced the human genome and now directs the National Human Genome Research Institute."

Another problem could be the sporadic occurrence of paternally inherited mitochondrial DNA in the offsprings because all the calculations used by 23andME's Maternal Ancestry Service based on the assumption that mitochondrial DNA is only inherited maternally.

- preventive lifestyle based on personal genetic information.

- The life extension bonus effect of personal genome services: +10 years?

- social networking XY.0 based on shared genotypes

- redefinition of genetic privacy rights

- health insurance problems

- the rise of genetic literacy and biological knowledge amongst laymen, but half--digested genetic information could easily be misleading

23andME

Professional Media:
Wired: 23AndMe Will Decode Your DNA for $1,000. Welcome to the Age of Genomics

Slideshow: The Business of Genomics

David Ewing Duncan: Welcome to the Future
New York Times: My Genome, Myself: Seeking Clues in DNA

Blogosphere:

The Genetic Genealogist: 23andMe Launches Their Personal Genome Service

Pimm: inF.A.Q. for 23andMe: what if I have mitochondrial DNA from Pa?

Pimm: The life extension bonus effect of personal genome services: +10 years?

Gene Sherpas: Not with a Bang...The Death of Personalized Medicine

Signals

Welcome to DIY (do it on yourself) biological research

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 22:43:20 -0700

Description

Last year Attila Csordas told bio-DIYers, "do not hesitate:"

[I]n the not so distant future, self-aware citizens may manage their own stem cells, grow them in the garage, and store them in the fridge. It could be a form of autonomous medical self-insurance.

Incredible as it may sound, the basics of molecular biology - what is DNA, how genetic information is coded, how it turns to RNA, which base triplets fits to which amino acids, the building blocks of proteins, that make up your body - can be learnt within 2 hours. Another intensive two weeks in an official lab with an instructor and you can work with them.

Csordas argues that if you can learn the basics of PCR and in vitro cell culture, you can do it.

Baris Karadogan (at From Istanbul to Sand Hill Road) draws out some implications:

Welcome to open source science, welcome to do it yourself biology.... With so much information on the Internet and such ready access to scientific data, what Attila wrote about could very well be commonplace in 5-10 years. This is a world where people could be "playing around" with their own biology. I see two big impacts right away.

First, tinkering is the best way to invent things, and this would really push the envelope in scientific and practical discovery. Second, if you think governments are having a hard time figuring out the laws to govern file sharing, let's see how they'll deal with "amateur genetic engineering". This will be a huge issue. Imagine people coming up with "user generated biotechnology".

Attila Csordas, http://attilachordash.newsvine.com/_news/2006/04/23/155889-biotech-diyers-do-not-hesitate
Baris Karadogan, http://baris.typepad.com/venture_capitalist/2007/01/the_ultimate_em.html

Signals

The Advent of Molecular Archaeology

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

The advent of archaeology at the molecular level thanks to advancements in genetics, chemistry, and physics is expected to lead to a new level of precision in archeological research and enable better understanding of past events and cultures.

Advancements in genetics, chemistry, and physics are enabling archaeologists to solve many archaeological and historical mysteries by examining evidence at the molecular level. DNA analysis can be used to reconstruct the subsistence and cultural activities of ancient peoples with an accuracy that is not possible with traditional archaeological methods. Borrowing from chemistry, archaeologists can reconstruct diet and local environment from a suite of stable isotopes. And drawing on physics, they can use particle accelerators to determine the age of specks of organic material with great precision.

Already DNA analysis is being used for such tasks as tracking population lineages, determining the species of ancient plant and animal materials, tracing bloodlines, and determining the sex of ancient human remains. Here are a few cases in point:

At the site of Askalon, an ancient city in the south of Israel, archaeologists discovered bodies of 100 infants behind a bathhouse. It was believed that they were the remains of unwanted girls, because female infanticide was common during those days. Gender determination by DNA analysis revealed skeletal remains of as many boys as girls. Armed with the DNA evidence, scientists concluded that the bathhouse was a brothel as well, and infant victims were unwanted babies of women working in the brothel.
The mitochondrial DNA (mtDNA) of Tyrolean Ice-Man has revealed a homology to today's population of the northern Alps.
Isolation of the DNA of tuberculosis pathogens in Peruvian mummies that date back 600 to 900 years has proven that Columbus and his successors did not bring the disease to the Americas.
DNA fingerprinting has helped scientists identify the remains of Josef Mengele in Brazil and the Romanov family in Jekatrinenburg.
DNA has been used to gather genetic information about a 4000-year-old Egyptian mummy.

Most physical anthropologists believe that studies of the haplotype distribution of mitochondrial DNA and Y chromosomes will become extensive and finely detailed. This would enable researchers to plot the movements of ancient groups with greater precision as well as bring a new level of precision to archaeological research overall."

This will be enabled by:

"Recent developments in genetics, physics, and chemistry
Development of the PCR (polymerase chain reaction) technique in the 1980s, which has made it possible to detect and characterise traces of DNA from as little as a single molecule"

Early indicators include:

Current use of DNA evidence to solve many archaeological and historical mysteries

What to watch:

Genetic mapping becomes cheaply available.

Signals

Nanowire Sensors for DNA Testing

Alex Soojung-Kim Pang — Tue, 23 Oct 2007 11:10:30 -0700

Description

Testing of DNA with nanowire sensors is likely to replace traditional DNA tests, making such testing less expensive, faster, and more widely available as a diagnostic tool.

Highly sensitive sensors that employ nanomaterial science could enable the optoelectronic and electrochemical detection of DNA. Such sensors could allow single-drop-sized samples of DNA, from blood, urine, or saliva, to be tested for viral DNA, a genetic disorder, or drug interactions. Inexpensive and fast tests based on these sensors could allow earlier disease detection and provide a way of genotyping patients that is lower cost than the microarrays currently used. The early lead that microarrays have in research however could become an advantage when genotyping moves into the clinical setting.

Aside from their use in DNA testing, electronic sensors based on nanoscience, unlike chemical tests, would be operationally convenient to use in field settings, and potentially capable of detecting a wide range of materials with clinical, defense, and environmental relevance.

At present, it is not clear which of the competing technologies for nanowire sensors (for example, lithography and self-assembly) will be most successful."

This will be enabled by:

Increased production and lowered cost of carbon nanotubes

Early indicators include:

Demonstration by Harvard University researchers that it is possible in real time to detect sequences of DNA that cause cystic fibrosis by using a sensor made from nanowires
Design by researchers at Hewlett Packard of a 50-nm silicon-based sensor employing lithographic patterning techniques for the sequence-specific detection of DNA in very small quantities

What to watch:

Manufacture of nanowire sensors based on one technology or another proves itself by resulting in rapidly falling cost per unit.
Genotyping moves into the clinical setting and nanowire sensors predominate over microarrays there due to their lower cost.