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Personal Genome Sequencing


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#1 kevin

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Posted 15 August 2003 - 11:08 PM


http://www.futurepun...ves/000123.html
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September 23, 2002
UK Start-up: Your genetic code in a day
The company's name is Solexa:


A British company says it is close to perfecting a gene sequencing method that could "read" someone's genome in a day.

From Solexa's web site:

Solexa was established in 1998 to develop and commercialize a revolutionary new nanotechnology, called the Single Molecule Array™, that allows simultaneous analysis of hundreds of millions of individual molecules.

We are applying this technology to develop a method for complete personal genome sequencing, called TotalGenotyping™. This will overcome the cost and throughput bottlenecks in the production and application of individual genetic variation data that are holding back the benefits to medicine that can flow from the genome revolution. Solexa’s technology will offer a potential five order of magnitude efficiency improvement, well beyond the range possible from existing technologies.

Our technical approach combines proprietary advances in synthetic chemistry, surface chemistry, molecular biology, enzymology, array technology and optics. Based on Single Molecule Arrays with the equivalent of hundreds of millions of sequencing lanes, we will deliver base-by-base sequencing on a chip without any need for amplification of the DNA sample.

To date we have raised over £15 million (€22 million; $23 million) in venture capital investment that has enabled us to make rapid progress with the development of our technologies. We have attracted a talented and multidisciplinary team of scientists to accelerate prototype development.

Solexa occupies its own customized 14,000 sq ft facilities in Cambridge, UK.

#2 kevin

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Posted 15 August 2003 - 11:29 PM

http://www.biomedcen...ews/20021004/04
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A cheap personal genome?Optimism and doubts expressed at discussion of $1,000 genome. | By Leslie Pray

BOSTON — Step right up and have your genome sequenced in a single afternoon. Or, why wait all afternoon? How about having it done within minutes – better yet, seconds? Such was the tone of predictions made during a panel discussion titled "The Future of Sequencing Technology: Advancing Toward the $1,000 Genome," held Wednesday evening, October 2, at the 14th International Genome Sequencing and Analysis Conference.

Not all of the speakers promised such fast turnaround times, but Susan Hardin of Houston, Texas based VisiGen Biotechnologies forecast that in two to four years her company will have developed the technology to sequence an entire human genome within a couple minutes. Not to be outdone, Eugene Chen told the audience that US Genomics' goal "is to be able to read your genome instantaneously," and that he expects the technology to make it possible to be up and running in about three or four years.

The pursuit of quick, affordable personal genome sequencing has been gaining momentum, amid growing expectations surrounding the healthcare potential of personal genetic testing. The ultimate personalized medicine tool, a personal genome sequence conveniently saved to a CD, is currently a luxury item. Former Celera chief, Craig Venter, is taking orders for full personal sequences at a price of $620,000 and UK-based Solexa has said it will soon offer consumers just-SNPs (nb: single nucleotide polymorphism) for considerably less. But the $1,000 genome is considered the point at which widespread personal sequencing will become economically feasible because both consumers and health insurers might be willing to pay for it.

Wednesday evening's discussion of technological progress toward that mark was co-moderated by Craig Venter, representing one of his three non-profit foundations, The Center for Advancement of Genomics, and Gerald Rubin of Howard Hughes Medical Institute. Participants also included George Church of Harvard University's Lipper Center for Computational Genetics, Trevor Hawkins of Amersham Biosciences, Tony Smith of Solexa, and Michael Weiner of 454 Corporation.

Both VisiGen and US Genomics' sequencing technologies, along with Solexa's, are single-molecule approaches, and single molecule detection is "absolutely a doable thing," Hardin told the audience. However, some questioned its feasibility. It would be wonderful if it worked, Weiner said after the session, but "show me the data." The technique has been around for 15 years, he told The Scientist, and there are still major limitations.

454's picotiter plate technology, which is not single-molecule based, currently achieves a rate of 2.4 million bases per day per machine. It may not be as fast as the others, but it is the closest to actually being available as a usable product, Church told The Scientist. Of all the new technologies discussed, Weimer agreed, only 454's picotiter plate and Church's 'polony sequencing' are currently totally functional.

Single-molecule or otherwise, the realistic price of mass personal genome sequencing was also raised. Reagents are particularly expensive and comprise about half the cost of sequencing, panelists noted. Increasing miniaturization and reducing reagent volumes are major challenges to reaching the $1000 genome, Hawkins told the audience. The ultimate goal of a $1000 genome is challenging but achievable, said Smith, although he would not say when.

The bottom line, Hawkins said, is that there are technologies that will be made available that can drop the cost down to around $30,000 per genome within the next two or three years. To get past that point, he said, we need a "new technology." In the meantime, $30,000 may not be within the means of the average consumer, said Hardin, but still it is considerable progress. "After all," she observed, "for a scientist, a thousand dollars is practically pennies."

Links for this article
14th Annual Genome Sequencing and Analysis Conference
http://www.tigr.org/...ac/agenda.shtml

US Genomics
http://www.usgenomics.com/

P. Moore, "Testing times ahead," The Scientist, September26, 2002.
http://www.biomedcen...ws/20020926/06/

Solexa
http://www.solexa.co.uk/

The Center for Advancement of Genomics
http://www.tcag.org/

Howard Hughes Medical Institute
http://www.hhmi.org

Lipper Center for Computational Genetics
http://arep.med.harvard.edu/

Amersham Biosciences
http://www.apbiotech.com/

454 Corporation
http://www.454.com/

Edited by kevin, 15 August 2003 - 11:53 PM.


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#3 kevin

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Posted 15 August 2003 - 11:37 PM

Public release date: 12-Oct-2002

Contact: Claire Bowles
claire.bowles@rbi.co.uk
44-207-331-2751
New Scientist


Special report: Personal genomics
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GENOME sequencing is about to get personal. For more than a decade, thousands of researchers around the world have spent about $3 billion to complete the human genome project. It's not finished yet, but even when it is, we still will not have the genome of a single person: the official consensus sequence is based on DNA from 10 different people.
This is not good enough for some researchers. Their goal is to get very personal indeed. "We are proposing to give people their own sequence if they'll have it," says genomicist George Church of Harvard Medical School.

The allure of knowing your own genome is obvious. It holds many of the secrets of your life- and death. It could, for example, reveal if you are likely to develop heart disease or Alzheimer's. Church and other experts think this is no longer a pipe dream. They believe that in less than a decade, people will be able to get their own genomes sequenced for about the price of a laptop or a flat-screen TV. When that happens, the thinking goes, a whole new industry of personal genomics will take off.

The idea is gathering momentum thanks to Craig Venter, the eccentric scientist-entrepreneur who raced government-funded labs to decode the human genome. Earlier this year, he was ousted from Celera, the genome company he founded. But he has bounced back with a plan for a massive non-profit genome sequencing centre in Maryland. And in a widely publicised bid to attract funding for the centre, Venter says he wants philanthropists to donate a few hundred thousand dollars each. In exchange, he'll hand them the sequence of their genomes' coding regions- the 2 per cent or so that encompasses all known genes.

Posted Image
Craig Venter

For the record, Venter tells New Scientist he is not "taking orders" from people or setting this up as a commercial service, as some reports have stated. Rather, his goal is to collect sequence information from lots of people, to learn more about the link between genetic variation and disease.

But the centre's goal is also to take DNA sequencing to a higher level, turning it into a fast, cheap technology. "As usual, Craig is accelerating the rate," says Church. "What will happen now is that people will take this seriously."

That's no small task, since the technology has advanced more slowly than expected. The standard method involves breaking a genome into short strands and making multiple copies of every short DNA fragment before it can be sequenced. The first generation of automated sequencers read about 5000 base pairs, or "letters", per day. Today's machines, which use an improved version of the same technique, sequence about a million bases a day. It's impressive, but not enough. With these machines it would still take millions of dollars and many weeks to sequence a person's genome, says Church.

Miniaturisation and high-throughput techniques can only do so much. They might reduce costs to $30,000 per genome, Trevor Hawkins of Amersham Biosciences told a conference in Boston last week. "But to get to $1000, it's going to take some new technologies," he said. One approach is to stick known strands of DNA on chips to "fish" for complementary strands in a sample. With information from the human genome project, Perlegen Sciences in California developed DNA microarrays that detect millions of sequences at a time. The company announced in August that it has worked out the genome sequences of 25 people with the arrays. But at $1.5 million a genome, the cost is still prohibitive.

Perhaps the greatest excitement surrounds a series of methods to sequence single DNA molecules- an approach that does away with the need to make lots of copies of short segments. These could let sequences be read with unprecedented speed.

US Genomics in Massachusetts has developed a machine that scans a single DNA molecule 200,000 bases long in milliseconds. For now, it untangles the DNA and scans the molecule by picking out fluorescent tags located every 1000 base pairs or so. But chief executive Eugene Chan says the company expects to be able to read sequences one base at a time in three or four years. "Our goal is to sequence the genome instantaneously," he says.

Other firms, such as Texas-based VisiGen Biotechnologies and British company Solexa of Essex are also trying the single-molecule approach. (Visigen Tech)The consensus is that it will take at least five years before sequencing technology reaches the point where it's fast and cheap enough to make personal genomics feasible. What's more, it also has to be highly accurate.

That's because our genomes are 99.9 per cent identical. It's the 0.1 per cent differences that determine if we're blonde or brunette, if we'll get heart disease or not. So accuracy is likely to be a tricky issue for personal genomics companies: get a single base pair wrong and a client may conclude they are about to die of a hereditary disease.

Assuming the technology gets this far, what will your genome reveal? Researchers may know a fair amount about genes that cause relatively rare diseases, such as cystic fibrosis, but we're still in the dark about mutations that predispose people to more common problems- cancers, heart conditions or mental disorders such as schizophrenia. "We are really just at the beginning of the field," says David Reich of the Whitehead Institute in Cambridge, Massachusetts.

At the moment, giving somebody a CD containing their complete sequence would be as useful as giving them a book in a foreign language, adds Brad Margus of Perlegen. It would be useless without the right software and the knowledge needed to interpret it.

Yet as sequencing becomes affordable, Margus thinks we'll learn how genetic variation and lifestyle affect the risk of disease, as well as other characteristics. "The technology is going to drive the understanding of the meaning of genomic information. It goes hand in hand," says Chan.

Only then will personal genomics companies be able to offer consumers reasons for knowing their genomes beyond sheer curiosity. And by that time the industry will have to convince people that having their whole genome sequenced will be better than paying for single or multiple gene tests, which a whole different set of companies is working on.

Both avenues will have their pros and cons. But one thing could tip the scale in favour of sequencing. By taking your sequence home and analysing it, you might be able to avoid infringing a company's patent, which is already rumoured to be a big worry for the makers of diagnostic chips. Licensing fees are expected to pile up, increasing the price of the chips, since many genes being tested for will be patented.

How ironic, then, if decoding people's genomes is what ultimately sets them free from the widespread privatisation of their genes.



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Written by Sylvia Pagan Westphal, BOSTON

New Scientist issue: 12 October 2002

PLEASE MENTION NEW SCIENTIST AS THE SOURCE OF THIS STORY AND, IF PUBLISHING ONLINE, PLEASE CARRY A HYPERLINK TO: http://www.newscientist.com

#4 kevin

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Posted 16 August 2003 - 12:02 AM

A really good overview of personal genomics sequencing.

http://www.solexa.co...2002_Solexa.pdf

#5 DJS

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Posted 16 August 2003 - 08:04 PM

Ok Kevin,

So in laymens terms, what would me getting my personal genome sequenced mean? Would it have real predictive value? Would I be able to look at it and say ok, as I get older, my chances of getting diabetes are 40% higher than the population at large based on my genome? Or if I have children, would I be able to look at my genome sequencing and say ok, I have a dormant gene that may express itself in my child as Autism?

Is this what the medical community is chirping about when they say there will soon be individualized medicine?

And finally, how much truth is there when people say that even though we can sequence our genome we still don't have the means to translate it into useful information?

Thanks
Kissinger

#6 kevin

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Posted 16 August 2003 - 09:25 PM

Kissinger,

Even though the Human Genome Project has finally led to a fairly complete draft of our DNA, we still don't know alot about the genes that are contained in it. That's what is meant when they say, "Sure you'll have your sequence, but it won't mean anything.". This is more than a little inaccurate. These statements were made in late fall of 2002 and reflect the position at that time of the European Society for Medical Oncology that "Despite the immense potential impact of the Human Genome Project on clinical care, there are almost no clinical services available to cope with the demand" A year later, we still haven't seen an impact of the Human Genome Project in the local Medi-Center, but there are almost daily press releases of genetically linked diseases, important ones like colon cancer, bipolar disorder, and lupus for only a few and the pace of discovery is accelerating.

The more we understand which genes and mutations give rise to different disease syndromes the more useful our own personal genetic code will be. An approach that will accelerate the elucidation of the functionality of the genes in the human genome will be in the comparison of the genetic codes of multiple organisms.

I think personal genome sequencing will be key in accelerating the funding of research into longevity and disease. Some people argue that if there isn't a treatment for a condition, they don't want to know if they are predisposed to having it. I think these types just don't want to take responsibility for their, or anyone else's well being and "let sleeping dogs lie". Thankfully, I believe these people to be in the minority, and that largely, if given the opportunity at reasonable cost, the 'forewarned is forearmed' mentality will be the one to prevail. If this is the case, can you imagine what hundreds of thousands of individuals who know they are predisposed to heart disease, cancer, or Alzhemiers would do to influence discoveries to avoid their 'personal' affliction.. ?
Almost anything I would expect... Just look at the amount of money garnered for AIDS and breast cancer research..and this is 'after the fact' cash..

If I knew I harbored the genes for Huntingtons, I would be MUCH more prone to donate and watch the news for developments.

Personalized medical service will mean treatments and lifestyle changes that will be tailored to your particular genetic make-up. Diet and nutrition requirements are actually quite different between individuals and what is good for one, is sometimes quite harmful for another. Recommended daily allowances of nutrients try to strike a common denominator but very often a person's biochemistry doesn't fit the 'average' and suffers from too much or too little of something. As well, as we age and get older, our requirements change and quite dramatic changes in diet may be in order to keep health optimal.

I look forward to being able to walk into my doctors office while he pulls up a holographic image of my innards and as he points to a particular area he can zoom in on the protein molecules that are responsible and further zooming can reveal the genetic code at the start of it all..

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#7 kevin

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Posted 18 August 2003 - 05:27 PM

Public release date: 14-Aug-2003

Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions


Hopkins is first US institution to obtain powerful genotyping system

Ahead of other U.S. academic institutions, The Johns Hopkins University School of Medicine and its McKusick-Nathans Institute of Genetic Medicine have pooled resources to obtain a commercial system capable of processing hundreds of DNA samples and determining up to 600,000 genotypes a day.
The $1.5 million system, purchased from Illumina Inc. (San Diego, Calif.), has been installed and tested and should be fully operational by September. Part of the shared genetics resources at Johns Hopkins, the system will use both premade panels of known genetic sequences and research-specific panels of genes, designed in-house, to identify genetic changes in DNA samples.

"In addition to offering a lower cost to researchers, our flexibility should set us apart from what is available from companies," says Alan Scott, Ph.D., director of Johns Hopkins' Genetics Resources Core Facility and one of the forces behind getting the new genotyping system. "Quite a few research programs here require genotyping hundreds to thousands of tissue samples, and other researchers may have been reluctant to take on such tasks because the work couldn't be done nearby. Now we'll be able to offer these services right here at Hopkins."

The new system, called "BeadLab" because of the technology it uses, can examine up to 96 different samples and determine more than 100,000 genotypes in a single experiment. A genotype is a description of an individual's sequence of genetic building blocks (A, G, T and C) and can be compared to others' to help scientists identify genes involved in disease.

Most of the human genome's 3 billion building blocks occur in the same order in all humans. But everyone also has occasional substitution of one genetic building block for another. If a particular spot has a common variation (i.e., some people have an "A" instead of the usual "C"), that position is said to have a single nucleotide polymorphism, or SNP (pronounced "snip"). Several million SNPs already are known.

Geneticists have successfully correlated SNPs or other mutations with the incidence of some rare diseases such as cystic fibrosis. But determining genetic contributors to and causes of such common diseases as cancer has been a difficult, piecemeal process because these conditions involve multiple genetic changes that combine to affect health or disease.

"This genotyping technology lets you rapidly survey what amounts to the entire human genome for regions linked to a condition, and then, separately, to delve into the fine detail of very small regions of DNA to figure out what's really happening," says Scott.

With the appropriate controls and experimental set-up by trained technicians, the system determines the genotypes of all the samples and produces a score that rates the accuracy of the result.

"These genotypes can then be correlated with patient characteristics, health, tissue type or whatever it is you're studying," says Aravinda Chakravarti, Ph.D., director of the McKusick-Nathans Institute. "Instead of spending years just to get genotype information across the genome, now we can spend our time analyzing the data, looking for multiple genes rather than finding them one at a time. With this system we're well on our way to being able to do large-scale studies of complex human genetic diseases and to investigating the biological basis of individuals' susceptibility to disease."

The Illumina system's BeadArray technology uses dimpled fiberoptic strands in bundles no thicker than a pencil lead, each holding tens of thousands of tiny beads. Each bead is labeled with one of up to 1,300 DNA tags to unmask the version of a specific SNP in the sample. The fiberoptic bundles are then arrayed as in a 96-well plate.

The new facility will be housed at the Johns Hopkins Bayview campus near the Center for Inherited Disease Research, a Johns Hopkins operation funded by a federal contract. As more researchers begin to need and use the technology, Scott hopes the system is used to determine roughly 200,000 genotypes per day.

Scott notes that the high-throughput genotyping system complements other services offered by the Genetics Resources Core Facility, including the DNA Fragment Analysis Lab and the DNA Analysis Facility. Both can determine research-specific genetic sequences that can't otherwise be studied.


###
On the Web:

The Genetics Resources Core Facility
http://grcf.jhmi.edu/

Illumina, Inc.
http://www.illumina.com

Johns Hopkins Medical Institutions' news releases are available on an EMBARGOED basis on EurekAlert at http://www.eurekalert.org and from the Office of Communications and Public Affairs' direct e-mail news release service. To enroll, call 410-955-4288 or send e-mail to bsimpkins@jhmi.edu.

On a POST-EMBARGOED basis find them at http://www.hopkinsmedicine.org



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#8 kevin

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Posted 09 September 2003 - 05:36 AM

Link: http://www.futurepun...ves/001317.html
Date: 05-29-03
Author: Randall Parker
Source: Future Pundit
Title: Venter, Duke U Initiate Search For Genetic Causes Of Disease


Venter, Duke U Initiate Search For Genetic Causes Of Disease

Craig Venter says at his new Center for the Advancement of Genomics DNA sequencing will cost only 1 dollar per 800 base pairs.

At his new center, the cost of sequencing DNA will be as low as $1 for 800 DNA units, he said, a substantial saving on current costs.

That works out to about 0.125 cents per base pair. Let us put that in some recent historical perspective. In 1998 DNA sequencing cost 50 cents per base pair.

When we started the project in the late '80s, it cost about $5 to sequence a base pair; that has dropped to about 50 cents per base pair,

As of November 2002 the U.S. Human Genome Research Project of the US Department of Energy was quoting a cost of 9 cents per finished base pair. This makes comparisons a bit difficult. The effort to sequence the human genome involved repeated sequencing to look for errors. Is Venter quoting a verified sequencing cost of 0.125 cents per base pair or just a first pass cost that low? Either way his cost is at least an order of magnitude lower than the DNA sequencing costs of just a couple of years ago. However, his cost still puts the cost of sequencing a person's complete genome (about 2.9 billion base pairs) in the millions of dollars. Costs are still a few orders of magnitude too high for the sequencing of one's own genome to become commonplace.

There are research groups and venture capital start-up companies working on more radical advances in DNA sequencing. See here and here for example.

Venter's institute has signed an agreement with Duke University to collaborate to discover the genetic contributions to various diseases and to develop faster and cheaper tests for genetic variations that contribute to disease.

Part of their goal is to identify genetic hiccups found in major illnesses such as heart disease, cancer, infectious diseases, even sickle cell anemia. But it’s also to find accurate, inexpensive tests that will tell individuals what’s likely to make them ill long before they’re in danger, so they can opt for preventive measures — maybe even genetic "repair patches."

As the cost of DNA sequencing continues to drop the scale and number of efforts to discover the genetic causes of diseases will continue to rise. Most importantly, the rate at which the genetic causes of disease are discovered will steadily accelerate year after year until the vast bulk of the genetic variations that contribute to disease are identified.

By Randall Parker at 2003 May 29 12:56 AM

#9 kevin

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Posted 09 September 2003 - 05:45 AM

Link: http://www.futurepun...017.html#000017
Date: 09-04-02
Author: Randall Parker
Source: Future Pundit
Title: Nanopore technology: sequence your DNA in two hours!


September 04, 2002
Nanopore technology: sequence your DNA in two hours!

Current DNA sequencing techniques involve taking the DNA from a person or other organism and then making billions of copies of it to run thru sequencing machines. This is slow, expensive, and error prone. Back in 1989 UCSC professor David Deamer first conceived of the idea of making nanopores thru which a single strand of DNA would pass at a time and as the strand passed thru the nanopore its changing electrical pattern would be used to read each successive DNA base (each letter location in the genetic code) via sensors built into the nanopore structure. This approach holds the potential of allowing for miniaturization, elimination of lots of expensive reagents, and to speed sequencing by many orders of magnitude.

One of the teams attempting to develop nanopore DNA sequencing technology is at Harvard. From Harvard Biology Professor Daniel Branton's home page:


A novel technology for probing, and eventually sequencing, individual DNA molecules using single-channel recording techniques has been conceived. Single molecules of DNA are drawn through a small channel or nanopore that functions as a sensitive detector. The detection schemes being developed will transduce the different chemical and physical properties of each base into a characteristic electronic signal. Nanopore sequencing has the potential of reading very long stretches of DNA at rates exceeding 1 base per millisecond.

Biophysics Ph.D. candidate Lucas Nivon, who works in the lab of Professor Dan Branton has this to say about the potential for nanopore technology:


Professors Dan Branton and David Deamer developed a new way to sequence single-stranded DNA by running it through a protein nanopore. Using this method, we could potentially sequence a human genome in 2 hours.

Well, 1 base per millisecond translates into 86 million bases per day. With a 2.9 billion size human genome it would take slightly over a month to sequence an entire genome. But Nivon's 2 hour estimate is plausible because many nanopores could be placed into a single device. With 500 nanopores in a single device the human genome could be decoded in less than 2 hours. The first article in the list below uses the 500 nanopore example though they quote a 24 to 48 hour sequencing time. Possibly different generations of this technology are being referenced to come out with different predicted sequencing times.

For a more detailed discussion of this topic see these articles:

A Genetic Hole in One
U.S. GOVERNMENT TO PUSH NANOPORES, MOLECULAR ELECTRONICS IN NEXT DECADE
Lab Rat: No mere hole in the wall
Harvard Nanopore Group Selected Publications
Harvard materials scientists working with Branton and Golovchenko
The USCS Nanopore Project
UCSC NANOPORE DETECTOR SHOWS DISCRIMINATING TASTE IN DNA MOLECULES

Posted by Randall Parker at September 04, 2002 12:16 PM

#10 kevin

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Posted 09 September 2003 - 05:50 AM

Link: http://www.futurepun...597.html#000597
Date: 11-11-02
Author: Randall Parker
Source: Future Pundit
Title: US Genomics May Drive DNA Sequencing Costs Way Down


November 11, 2002
US Genomics May Drive DNA Sequencing Costs Way Down

US Genomics is developing technology to do linear single strand DNA analysis. They are not the only ones attempting this and it is not clear how successful they will be. But they have made progress jumping over some of the hurdles that they face with their approach. Notice the high speed per minute. At that rate they could in theory read the entire 3 billion DNA sequence of a human genome in less than 11 days..

Chan has developed a way to spool out the tangle of DNA in a chromosome using a 'nanofluidic' chip smaller than a computer key. Fluid flowing through the chip draws the DNA through an array of pegs like bowling pins. One end works loose and is drawn into a funnel at the end.

Rather than sequencing every letter, Chan and his team spot the differences between individuals — and use the reference genome to fill in the rest. Fluorescent tags stick to variable spots; a detector reads their order as they flow past. The speed-reading technique gets through around 200,000 letters a minute, he claims.

They are trying to develop the ability to unravel and read thru a genome as fast as a regular cell can when it replicates its genome during cell division.

The company's technologies are premised upon the direct and linear reading of large sections of genomes. Linear analysis is powerful because there is no upper limit on the size of DNA that is read. Furthermore, this is the method which nature has perfected over millions of years. DNA, during cell division, is replicated with DNA polymerase, an enzyme that tracks along DNA in a linear fashion. Identification of the bases is mediated by base-pairing and enzyme-DNA specific interactions. By reproducing nature's method of DNA reading, the highest readout speeds are possible. A human cell can replicate and read its DNA in less than thirty minutes. The company's technology is a biophysical rendering of the polymerase-DNA interaction and allows for speeds on the same time scale as nature's DNA polymerases.

U.S. Genomics's technology platform, the GeneEngine™, has two components, (1) nanotechnology systems for positioning DNA so that it can be read linearly (broadly termed DNA Delivery Mechanism(s)™) and (2) detection technologies that allow the reading of information from the DNA Delivery Mechanism(s)™. The combination of different DNA Delivery Mechanism(s)™ with particular technologies makes possible different applications in genomic analysis, such as complete genome analysis, sequencing, polymorphism analysis, and gene expression determination.

Here's the announcement for their patent for moving single DNA strands past a reader sensor.

Woburn, MA (JUNE 13 2001) – U.S. Genomics announced today that its first patent has been granted by the United States Patent and Trademark Office (6,210,896 Molecular Motors). The issued patent covers the first of a suite of proprietary techniques that U.S. Genomics has developed to allow the direct, linear reading of extremely long sequences of DNA.

Specifically, the patent covers the Company's technology for using molecules that interact with cellular polymers (such as nucleic acid -- DNA or RNA) in such a way that the molecules cause the polymers to move. The segments of the polymer that are moved by the "molecular motor" flow past a fixed point, emitting specific signals that reveal genetic information embedded on the strand of nucleic acid.

Eugene Chan, Chairman and CEO of U.S. Genomics, commented, "The granting of this first patent for U.S. Genomics is a validation of our approach to direct linear analysis of DNA. Modeled after the nearly instantaneous readings of DNA that natural cellular machinery executes, our approach to deciphering and understanding genetic information is directed towards complete-genome analysis - reading the entire sequence of genetic coding contained in a full, unbroken strand of DNA."

U.S. Genomics has developed the GeneEngine™, a set of laboratory devices that enable researchers to uncurl and separate individual strands of DNA or RNA which are then run through a microarray sequencer in extremely long, unbroken, linear segments. The genetic information captured through such direct linear readings is relatively much more comprehensive and integrated than data available through other current techniques. The molecular motors covered in this first patent provide the physical mechanism for moving the strands of DNA through the sequencer.


US Genomics is getting US military money to develop their technology to detect bioweapons attacks:

Woburn, MA (September 04, 2002) – U.S. Genomics announced today it was awarded a $499,500 contract by the Defense Advanced Research Projects Agency (DARPA) to examine the use of the Company’s direct linear DNA analysis technology to detect Class A pathogens, such as anthrax and smallpox. The contract will enable the company to study the use of its GeneEngine™ technology as a tool to create genomic maps or signatures of organisms; such maps have the potential to enable very rapid detection and identification of deadly bacteria.

While they do not sound like they are going to be ready to ship fully working products any time soon they have entered into an agreement The Wellcome Trust Sanger Institute to try out their GeneEngine technology in the study of genetic variations.


It is hard to interpret the announcement with The Wellcome Trust Sanger Institute. When will US Genomics deliver usable technology and what will that initial technology be capable of?

Woburn, MA (January 28, 2002) – U.S. Genomics and The Wellcome Trust Sanger Institute have entered into a collaboration to examine the use of U.S. Genomics’ direct, linear DNA analysis technology in research on the human genome. The partnership will study the use of this new technology to investigate human genetic data at a level of complexity, comprehensiveness, and accuracy not previously studied. The collaboration marks the first application of U.S. Genomics’ technology in an outside research setting.

Under the agreement, The Wellcome Trust Sanger Institute and U.S. Genomics will jointly employ their scientific expertise to conduct genetic research using the GeneEngine™ technology and other aspects of U.S.Genomics’ technology platform. The research collaboration will explore the application of U.S. Genomics’ technology to human genetic analysis at the highest level of detail and complexity. Financial terms of the agreement were not disclosed.


If we step back and look at it from a higher level what is interesting about this company and others like it is that venture capitalists are funding attempts to drive down the cost and accelerate the speed of DNA sequencing by orders of magnitude. Some of these companies will succeed. A lot of progress has already been made.

The US Genomics press releases are here.

#11 kevin

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Posted 26 September 2003 - 04:10 AM

Link: http://www.tcag.org/news.html
Date: 09-25-03
Author: -
Source: The Center for the Advancement of Genomics
Title: UCSD-TCAG Collaboration to Focus on Transformation of Genome-Based Knowledge Into Health Benefits


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UCSD-TCAG Collaboration to Focus on Transformation of Genome-Based Knowledge Into Health Benefits




LA JOLLA, Ca., Sept. 25 (AScribe Newswire) -- The University of California, San Diego (UCSD) and The Center for the Advancement of Genomics (TCAG) in Rockville, Md., today announced a formal collaboration in genomic medicine that combines large-scale human genome analysis with innovative medical research. Through this new collaboration, the two organizations will conduct genomic studies aimed at elucidating the links between multi-gene associations and the prediction and outcome of disease, with the goal of moving patient treatment closer to personalized drug therapy geared to an individual's genetic makeup.

Palmer Taylor, Ph.D., dean of the UCSD School of Pharmacy and Pharmaceutical Sciences, and J. Craig Venter, Ph.D., president of TCAG, announced the agreement at groundbreaking ceremonies for the new UCSD School of Pharmacy and Pharmaceutical Sciences building on the UCSD campus in La Jolla.

"We are pleased to be working with UCSD as this collaboration unites the high-throughput DNA sequencing and analysis prowess of our scientists at the J. Craig Venter Science Foundation Joint Technology Center (JTC) with the internationally renowned clinical researchers at UCSD," Venter said.

"Craig Venter is a pioneer in genome sequencing and analysis who brings us polymorphism discovery and characterization on a scale that enables the investigation of the genetic basis of complex disease and therapeutic response traits in large populations," Taylor said. "This partnership brings together unique resources from both groups. TCAG will have access to a well characterized patient base with defined phenotypes, while UCSD benefits from unparalleled genomic analysis and sequencing capabilities."

Under a multi-year Memorandum of Understanding (MOU), which outlines the details of the agreement, TCAG and UCSD will begin their collaboration focusing on hypertension and cardiovascular disease. According to the United States Centers for Disease Control and Prevention (CDC), cardiovascular disease is the number one cause of death in the United States, and there are approximately 61 million people living with some form of the disease. Clearly, there is an unmet medical need that both groups hope to address through the application of genomics technology.

The hypertension study is part of an emerging field of individualized medicine or "pharmacogenomics," where treatment moves beyond the "one-size-fits-all" approach to drug therapy and allows the development of individualized treatment plans based on genetic profiles. Using genetic indicators, physicians and pharmacists can determine in advance which drugs will work best for specific individuals and which are more likely to cause harmful side effects, and prescribe the most effective therapies.

While most humans share 99.9 percent of the same genetic sequence, scientists are discovering differences located within the genome (the DNA or hereditary material) in cells throughout the body. It's these differences that are the focus of the UCSD-TCAG partnership.

"The agreement provides an exciting opportunity to apply the power of genomics systematically to the practice of medicine and therapeutics," Taylor said. "Combining sequence information coming from targeted genes with clinical phenotypes, we should be able to identify the most appropriate therapy for specific individuals."

Venter added "We envision a world in the near future where genomics becomes a common weapon in the physician and individual's arsenal against disease. Through collaborations like this one and others that TCAG is involved in, we hope to move the timetable forward the genomic revolution to enhance all of our lives."

In the hypertension study, UCSD obtains DNA from a large group of patients, and sends it to TCAG for sequencing, which is a process for determining the precise order within a gene of the various nucleotides, or basic molecular components of DNA. Sequencing is applied to a jointly pre-selected set of genes in which polymorphisms may be linked to certain phenotypes. UCSD researchers simultaneously run tests to determine phenotypic information specific physical characteristics and medical measurements for each patient. Included are measurements of blood pressure, blood flow, release of adrenaline, vascular reactivity and various tests measuring patient responses to drugs and drug doses. The polymorphism data from the sequenced DNA will then be analyzed in conjunction with the phenotypic information using information technology-enabled approaches that compare genetic variations to disease characteristics and drug responses.

Under the direction of Daniel O'Connor, M.D., UCSD professor of medicine, the hypertension study began two years ago with a $2.9 million, four-year grant from the National Heart, Lung and Blood Institute as part of the NIH Pharmacogenomics network coordinated by the National Institute of General Medical Sciences.

Noting that UCSD is excited to be working with TCAG, O'Connor said "in this genome era, it is vitally important to have the power of a genome center that brings state-of-the-art technology to large scale sequencing. On top of that, TCAG's informatics and information technology capabilities are truly differentiating. We are delighted to be working with Craig and his team."

Thus far in the project, UCSD researchers have drawn DNA from 2,000 individuals and expect to collect another 500 samples over the next year. Preliminary results from these studies will be announced next month at the annual meeting of the Society for Human Genetics in San Francisco.

Initial goals of the UCSD/TCAG genomic-based medicine collaboration:

To integrate high-throughput DNA sequencing technologies and state-of-the-art analysis with distinctive medical expertise by re-sequencing and genotyping the relevant genetic material (genes and regulatory regions) of selected patients who are being studied by UCSD physicians. By sequencing the DNA of this patient population and associating these profiles with phenotype and disease outcomes, TCAG and UCSD researchers plan to correlate genetic variations to disease states to be able to initiate preventive steps or earlier treatment of disease.
To focus initially on major disease areas, including cardiovascular disorders, infectious diseases, and obesity-related illnesses.
To leverage the unique high-end computing center that TCAG has as part of its Joint Technology Center, a next generation, high-throughput DNA sequencing center. Currently the Center has the capacity to sequence 45 billion base pairs of DNA per year.
The Center for the Advancement of Genomics (TCAG) is a not-for-profit policy and research center dedicated to advancing science and medicine through education and enlightenment of the general public, elected officials, and students. TCAG will seek to better understand evolutionary issues, broad social and ethical issues such as race as a social concept rather than a scientific one, and combating genetic discrimination. TCAG will also focus on the public issues associated with biology/genomics in mitigating greenhouse gas concentrations and biological energy production. TCAG is a 501 © (3) organization.

The UCSD School of Pharmacy and Pharmaceutical Sciences is an integral part of the robust academic and research environment of the UCSD Health Sciences, which also includes the UCSD School of Medicine and UCSD Healthcare. Ranked as one of the world's leading public universities, and a top-ranking research center, UCSD also serves as an engine for pharmaceutical and biotechnology development in the region. Academic and research programs within the School of Pharmacy and Pharmaceutical Sciences emphasize the post-genomic era of drug development, including research into specialized medications tailored to individual needs. Surrounding the UCSD campus are numerous research and development companies devoted to biotechnology and pharmaceutical development, including more than 150 developed by or with UCSD faculty.

#12 kevin

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Posted 08 April 2004 - 07:44 AM

Link: http://www.futurepun...ves/002038.html

From The Future Pundit



DNA Sequencing Costs Continue to Decline
Biotech instrumentation company Affymetrix has announced a new instrument for mapping DNA Single Nucleotide Polymorphisms (SNPs) which Affymetrix claims is much cheaper to operate than previous instruments designed for this purpose. SNPs are locations in the genome where not all humans or all members of another species have the same the DNA letter. The new Affymetrix instrument will reportedly lower the cost of human DNA SNP testing to 1 penny per DNA letter.

The 100K builds on the innovative, scalable, easy to use assay that Affymetrix pioneered with the GeneChip Mapping 10K Array. The 100K allows researchers to genotype over 100,000 SNPs using just two reactions. Previously, genotyping 100,000 SNPs would have required 100,000 PCR reactions, a hurdle that made this kind of research impractical. Before the advent of 100K, the commercial product for genotyping the most SNPs was Affymetrix' Mapping 10K.

“The power of 100,000 SNPs in a single experiment is enabling researchers to attempt unprecedented genetic studies at a genome-wide scale,” said Greg Yap, Sr. Marketing Director, DNA Analysis. “The GeneChip Mapping 100K Set is the first in a family of products that will enable scientists to identify genes associated with disease or drug response across the whole genome instead of just studying previously known SNPs or genes, and to study complex real-world populations instead of simple ones. To do this, we are making large-scale SNP genotyping not only quick and easy, but also affordable -- about 1 cent per SNP.”


About half of the SNPs on the 100K set are from public databases, while the other half are from the SNP database discovered by Perlegen Sciences, Inc. All of the SNPs on the 100K set are freely available and have been released into the public domain. Because the assays and arrays used in the 100K set are extremely scalable, more SNPs from both public sources and the Perlegen database will be added to next generation arrays.

Just a couple of years ago the cost of SNP assays was at about 50 cents per SNP. Industry analysts at the time were predicting SNP costs to fall to 1 cent per SNP within 2 years and sure enough if Affymetrix's press release is realistic those costs are just about to fall to the predicted 1 cent per SNP.

To put that number in some useful perspective, there may be about 10 million SNPs in humans but perhaps about only a half million SNPs that are in areas of the genome that affect human function. Most of the SNPs are in junk regions. The 500,000 estimate of functionally significant SNPs is a scientific guess at this point and could easily be off by a few hundred thousand plus or minus. But once those 500,000 SNPs are identified (which could easily take a few years yet) the cost of 1 penny per SNP to test them all would cost about $5,000.00 per person in US dollars to test a single person's complete genome for SNPs. The real cost would be higher since samples of portions of the genome would need to be isolated for experimental runs. The real cost might easily be several times that amount. That still wouldn't provide a complete picture of a person's genome since there are few other kinds of genetic variations (e.g. short tandem repeats or STRs). But SNPs are responsible for most genetic differences within a single species.

At this point the decline in SNP testing prices is useful chiefly to scientists since we don't know which SNPs are important let alone how they are important. Still, the lower costs for SNP testing will accelerate the rate at which important SNPs are identified and that will bring closer the day when it makes sense to for individuals to go get complete SNP testing.

Full DNA sequencing is also at about 1 cent per DNA letter.

Our price is competitive at just $.01 per base per sample, all inclusive. For example, total sequencing for a 7 Kb region on 48 samples would cost a total of 7000 x 48 x $.01 = $3,360. This pricing structure makes SNP discovery project estimates straight forward, avoiding the possible uncertainty of estimating the exact number of PCR amplicons, sequencing reactions, etc.


This price would make a complete 2.9 billion letter human genome sequencing for a single person cost about $29 million dollars. But it would really cost several times more than that since sequencing has to be done multiple times to catch errors in the sequencing and there are sections of the genome that are hard to sequence. Since whole genome sequencing is much more epensive ways to lower the cost of the SNP testing is what is attracting the most interest. When SNP testing costs by fall another order of magnitude the cost will be low enough for at least the more affluent among us to want to pay for personal SNP tests. Once the costs fall yet another order of magnitude SNP testing for the masses will become common place. My guess is that given the rate at which SNP testing costs continue to fall and the predictions of industry figures of much cheaper SNP testing we are at most 10 years away from the point of general population large scale SNP testing..

#13 manofsan

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Posted 08 April 2004 - 08:20 PM

Cool post, thanks :)

But the Affymetrix chip and price quote is not for number of bases sequenced (ie. 2.6 billion), but for number of SNPs sequenced (ie. 100K)

So that pricing is much more manageable for 100K than it is for 2.6B, so don't despair.

I'm still hoping for the true base-by-base single molecule personal sequencing being done cheaply and instantaneously using nanopore or whatever other kind of lab-on-a-chip devices. Now that is a holy grail.

Anybody else have any word on what's happening with US Genomics, Solexa, Visigen, etc? Have they gone belly-up yet, or are they still plugging away and on track for the big goals?

#14 manofsan

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Posted 10 April 2004 - 06:37 PM

Here's a new article:

http://www.pharmagen...380/article.pdf

So it looks like the nanopore technology is coming along, but how long will it take to come to market, and how long before ordinary people like ourselves will be able to get their genomes sequenced without breaking the bank?

I also read at www.opgen.com that their optical-based gene sequencing technology which uses fluorescent markers is then already being used for high-speed sequencing. But this approach isn't quite as idealized as the nanopore approach.

#15 randolfe

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Posted 11 April 2004 - 01:47 AM

I think there is a rampant tendency among people in general, and Immortalists in particular, to "believe" every kind of medical miracle is just around the corner. I got caught up in such thinking and bought shares of Human Genome Sciences Incorporated and Abgenix for four to six times what they are selling for now. Optimism is a nice characteristic but don't put your money where your heart is.

For instance, in 1997, I was sure that cloning of a human embryo or even of a born human being was no more than a few years away. Well, it took them seven years to just get the first few human embryos cloned.

Figuring out how various genes interact and how to look at our individual genome to see our biological futures might be decades in coming. Biotech seems to produce more hype than results. With the exception of Amgen, most biotech enterprises drown in red ink and are financial disasters. Sad but true.

#16 manofsan

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Posted 11 April 2004 - 04:15 AM

Fair enough, but personal gene sequencing technology is something that would take things to the next level -- a "paradigm shift" if you will. I'm really not that interested in the mere stock peformance prospects, I'm really more interested in the prospects of advancing health, and in ultimately addressing the "human condition".

Here's an interesting article I read just a few minutes ago:

http://www.alwayson-...id=3576_0_1_0_C

Says things rather nicely, imho.

Things may always seem hyped at first, but the time it takes for reality to catch up to hype seems to be decreasing as we move forward. Harnessing our biological future may be decades in coming, but our very forward progress in this regard will buy us more time to see that future. Nifty how that works, eh?

In the early days of computers, many initiatives for innovation may have foundered, however as the field has matured and become more vibrant, ideas are ever more rapidly converted into tangible successes after conception. Unfortunately, that also leads to a proliferation of junk ideas (hence dotcom bubble, spam, viruses, hacking) which are able to grow beyond their utility to the marketplace. The same will happen in the field of genomic medicine. There will be many snakeoil salesman, much hype, but it's all part of that path towards success. Just as bubbles created a healthy skepticism which has been weeding out bad ideas in the e-marketplace focusing on true progress, so too will the same happen in the biotech marketplace.

#17 randolfe

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Posted 22 May 2004 - 06:48 PM

The ability to predict what our future holds for us by reading our genes is certainly welcomed by me. However, I had an exchange with bioethicist Arthur Caplan in which he argued that most people did not want to know their medical futures.

I thought knowing you were likely to die at 65 would lead you to retire earlier, enjoy whatever money you had, etc. Caplan seemed to think humans could only handle so much knowledge.

Don Spanton makes an interesting point about relevance on his children. We could do a profile on a developing embryo. That profile would probably lead many to terminate their pregnancies.

This would prevent those with handicaps from being born. It would probably preclude astro-physicist Hawking from being born because he would develop ALS. It might be used to make birth determined by whatever values the parents held. Perhaps musicians wouldn't want musically-ungifted children. Heterosexuals might abort any child that looked likely to be gay.

I, for one, have always supported the concept of "designer babies" on the basis that parents should have the right to choose the children they will spend years of their lives and much of their fortune raising. However, I find myself less sympathetic to the idea of terminating a pregnancy because the child will not have blond hair. Since "religiousity" is supposed to be an inherited trait, would those here use that as a litmus test? Would good Roman Catholics (like my parents) choose to abort me because I would be born an atheist?

These are sticky questions involved in the application of this technology. The Sun gives us all light and warmth and is necessary for life. However, the same Sun can burn us to death in the tropics and blind us in the artic. The benefits of technology like genome sequencing lies as much in its application as in its discovery.

#18 kevin

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Posted 22 May 2004 - 10:22 PM

randfolfe..

I had an exchange with bioethicist Arthur Caplan in which he argued that most people did not want to know their medical futures.


I remember hearing him say as much in his presentation at the IABG. The truth of the matter is, people spend gajillions of dollars to know the future by means that are more than a little suspect. It is hard to imagine that given the opportunity for a little more solidity to those predictions that people would forgo it. I think the reaction to widespread clinical genome sequencing, even at the single nucleotide polymorphism level, will be quite positive.. perhaps overwhelming. I look forward to the reaction of people who know their propensities for various ailments and how funding for science will most assuredly benefit. It is easy to ignore the plight of Alzheimer and diabetic patients when the coin on your fate has not yet landed...

I really do not see many people opting to terminate pregnancies for trivial reasons like hair color. Most parents simply want a healthy child. although when the ability to select for complex traits arises, I can see some rationale for doing so. Whether or not selecting the traits of children will actually result in those traits expressed in the individual is much less a certainty than those who are worried about introducing homogeneity into the population accept. Twin studies have long shown that environment plays a major role in the shaping of the individual, perhaps more than genetics, and I personally see no reason why the parents of a child, who are far more likely to be concerned with the child's welfare than anyone else, should not be allowed to give their offspring what they feel is the best chance at a happy and successful life.

That Stephen Hawking is a great thinker and physicist there is no doubt and certainly the world would be poorer today if he were to die. But would the world be poorer if he was never born? I don't think this line of reasoning reallly makes sense, because if he was never born.. there would be nothing to miss, we would be none the wiser for never having known his abilities. We can only guage loss by that which we already have.. not by that which we conjecture might come to exist. We had no prior knowledge of Stephen Hawking's arrival, nor of his discoveries and therefore would not have felt loss in his non-appearance.

I think that the point that many disabled make that they would likely not have been born had the technology been available to discern their condition should not be used as an argument against the use of techniques to select healthier children. Unless someone tries to make the argument that physical suffering is somehow a pre-requisite for greatness, I do not see how the practice of selecting the healthiest genes to pass on could possibly be anything but a positive development.

I find it somewhat amusing that you suggest that staunch Roman Catholics.. (I come from a family of fairly religious individuals.. ) would avail themselves of the very technology they currently eschew.. but stranger things have happened in the Catholic Church.. so why not.. :)

#19 kevin

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Posted 03 June 2004 - 07:58 AM

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Link: http://www.usatoday....reatments_x.htm

Although this doesn't exactly fall into the category of the uses of knowing one's normal DNA, it is a very good examle of the near term applications of gene profiling which will certainly lead to broader based usage.


New cancer treatments are coming made to order
By Liz Szabo, USA TODAY
When Cecily Harris was diagnosed with lung cancer in 1998, the outlook was grim. A tumor near her shoulder grew so big that it broke a rib. Chemotherapy left her too sick to see her grandchildren. She was given nine months to live.
Today, Harris is alive, well and working full time. With her cancer stabilized, her doctor says, the disease has been transformed from a death sentence into a chronic disease.

"I feel as well as a 76-year-old can feel," says Harris, who is from Englewood, N.J. "I'm one of the lucky ones."

Indeed, few cancer patients are as fortunate as Harris. Fewer than 5% of those diagnosed with advanced lung cancer survive five years or more. And only 10% of those taking the same cancer drug, Iressa, see dramatic benefits.

But doctors hope one day to see more patients like Harris.

Experts say her story illustrates the profound changes taking place in cancer research as scientists strive to perfect the new field of personalized cancer treatment. Researchers plan to share the latest news about such "targeted therapies" at the meeting of the American Society of Clinical Oncology beginning today in New Orleans.

"Patient-specific therapy might be the only way we will make inroads into this disease," says Harris' doctor, Roy Herbst, chief of thoracic oncology at M.D. Anderson Cancer Center in Houston. "Every patient's cancer is a little bit different."

The new drugs aren't cures.

But with therapies such as Iressa, researchers are beginning to tailor cancer drugs based on the genetics of a patient's tumor cells. And in a new field called "pharmacogenomics," doctors are developing ways to predict which patients might benefit — and which might suffer serious side effects — from therapies.

It could take five years or so before a wide array of such treatments is available to the average patient, Herbst says. Some might not work out. Yet many experts presenting research at the cancer meeting are optimistic.

By individualizing cancer treatments, doctors say they hope to help patients and avoid some of the grueling side effects of broad-based chemotherapy. Herbst compared Iressa — which Harris began taking in 1999 — to a "laser-guided bomb."

Targeting tumors

Iressa is one of a growing number of drugs which — rather than kill growing cells throughout the body — binds to an enzyme called the epidermal growth factor receptor, or EGFR, and turns it off. The enzyme, which is common in many kinds of cancer, acts as a switch that tells cells to divide and spread without dying.

Recently, researchers discovered one reason why Iressa works so well for some patients, but not for others. Certain tumors have mutated versions of that growth switch, which are particularly vulnerable to Iressa. Doctors are developing tests for the mutation so they can give Iressa to patients who will benefit most, or give the drug earlier.

EGFR also might play a key role in tumors of the breast, colon, ovary, head and neck.

The EGFR enzyme, researchers believe, sets in motion a complicated chain reaction that leads cells to multiply, invade surrounding tissue, develop their own blood supply and spread to organs without dying.

Drugs such as Iressa attack the EGFR molecule on the inside of the cell.

Another drug approved this year, Erbitux, blocks part of the EGFR molecule on the surface of tumor cells.

Doctors say they hope to put together "cocktails" of such drugs, attacking vulnerable links throughout the chain.

'Right drug for the right person'

Scientists might never have expected chronic myeloid leukemia — a cancer of the blood — to have much in common with a rare digestive tract cancer called gastrointestinal stromal tumors, says Harmon Eyre, chief medical officer at the American Cancer Society. As it turns out, however, both diseases respond to a drug called Gleevec, one of the first targeted therapies.

Instead of classifying cancers by organ, doctors are beginning to group them — and develop drugs — based on molecular structures, Eyre says. Because doctors already know so much about EGFR, many new therapies focus on that enzyme, although there are probably dozens of pathways and potential targets.

At the New Orleans conference, doctors plan to reveal the results of combining Tarceva with a drug called Avastin, approved in February, that starves tumors by cutting off their blood supplies.

Doctors note that targeted therapies, like all drugs, have limitations.

Some patients have become resistant to Gleevec, for example. Many promising therapies have not lived up to expectations. And experts note that even with so many new drugs, doctors still don't have enough options for patients.

Doctors say they wish they had more to offer the majority of patients who don't respond to Iressa. "We're just touching the tip of the iceberg," Eyre says.

"The real test will be when we have the right drug for the right person for the right disease."



Timeline

Medicines that target tumors

Targeted cancer therapies block specific molecular structures inside tumor cells and cause fewer side effects than traditional chemotherapy. The number of such drugs is growing, with many more in development.

• May 2001: Based on promising clinical trials, Gleevec granted "fast-track" approved by the FDA to treat chronic myeloid leukemia, a cancer of the blood and bone marrow. Gleevec was the first drug to directly turn off the signal of a protein known to cause cancer. It proved that targeting molecules inside tumor cells could kill them.

• February 2002: Gleevec approved to treat gastrointestinal stromal tumor, a cancer of the digestive tract.

• May 2003: Iressa approved to treat non-small cell lung cancer.

• February 2004: Erbitux approved to treat advanced colon cancer.

• February 2004: Avastin — which starves tumors by cutting off their blood supplies — approved to treat advanced colon cancer. It helped patients live longer and is the first to block angiogenesis, or blood vessel formation.

• April 2004: Scientists discover that Iressa works best on tumors with certain genetic mutations.

• June 2004: Researchers are expected to present data showing that Tarceva helps patients live longer.

#20 kevin

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Posted 29 October 2004 - 11:49 PM

Cross Reference Only:

XREF: http://www.imminst.o...476

#21 kevin

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Posted 01 March 2005 - 03:45 AM

Link: http://www.genengnews.com

This is just an abstract of a story in Genetic Engineering but is worth posting for the references to the companies vying to bring to market the cost lowering technologies of sequencing.




Race to Cut Whole Genome Sequencing Costs
Upon completion of the human genome sequence in 2003, a vision for the future of genomics research was put forth by the U.S. National Human Genome Research Institute (NHGRI) and published in Nature. In it, the NHGRI called for researchers to develop technology that would allow sequencing of a human genome for $1,000. This is no small order. Using today’s state-of-the-art capillary-based DNA sequencers it still costs well over $10 million to sequence three billion base pairs, the amount of DNA in the human genome. But many different groups, both commercial and academic, have taken on the challenge to drastically reduce the cost of DNA sequencing. With one race barely just finished, a new one is already under way. Last fall, the NHGRI awarded grants to spur the development of lower-cost DNA sequencing technologies. Representatives from Microchip Biotechnologies (Fremont, CA), Agencourt Bioscience (Beverly, MA), 454 Life Sciences (Branford, CT), LI-COR (Lincoln, NE), and Stephen R. Quake, Ph.D., of Stanford University were among the awardees developing near-term methods to sequence a human-sized genome for $100,000. According to the NHGRI, “there is strong potential that, five years from now, some of these technologies will be at or near commercial availability.”

#22 kevin

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Posted 12 April 2005 - 02:39 PM

Link: http://www.imminst.o...4&t=5990&hl=&s=

X-REF : http://www.imminst.o...990



Posted Image
Colour coding DNA promises cheaper sequencing
22:00 11 April 2005
NewScientist.com news service
Celeste Biever


By dyeing each of DNA’s four building blocks a different colour, a short section of the human genome has been sequenced by Jingyue Ju, a chemical engineer, and his colleagues at Columbia University in New York City, US. With more work, the technique could be used to sequence millions of longer DNA strands in parallel, slashing the cost of sequencing a whole mammalian genome.

The team added dyes to ordinary DNA building blocks, called nucleotides, according to which of the four DNA bases - adenine, guanine, cytosine and uracil - the nucleotides contained. Then they induced a single, 12-base strand of DNA from the human p53 gene to build a complementary copy of itself out of the modified nucleotides. The resulting strand of DNA codes for the original 12-base strand, but unlike the original can be sequenced easily because it is brightly coloured.

Traditionally, DNA sequencing is done using a technique called Capillary Array Electrophoresis (CAE) which sequences DNA strands by smashing them into millions of different fragments and then piecing them together again, using very sophisticated software. It works well, but faster, cheaper methods are needed as a maximum of 384 strands can be sequenced at a time and the technique requires expensive equipment and reagents.

“We have milked CAE for all the cost reduction we are ever going to get,” says Jeff Schloss at the National Human Genome Research Institute (NHGRI) in Bethesda, Maryland, US, which funds Ju’s work.

Touching bases
One commercially available alternative is pyrosequencing, which also detects nucleotides as they are added to a single strand of DNA, but it can lead to errors because it is harder to differentiate between a single base and a whole stretch of identical bases next to each other, says Elaine Mardis, a geneticist at Washington University in St Louis, US.

In contrast, Ju’s modified nucleotides contain a blocker that ensures that only one base can be measured at a time, even if there is a whole stretch of identical bases. Once its colour has been detected and recorded, the dye and the blocker are cleaved away using a laser light, allowing the next nucleotide to be added.

“This paper represents an exciting, impressive proof of principle, one important early step on the long path to really cheap genome sequencing,” says Chad Nusbaum, a geneticist at the Massachusetts Institute of Technology in Cambridge, US.

By funding this work, the NHGRI hopes to bring the cost of sequencing a mammalian sized genome down from $10 million to $1000 in the next 10 years - cheap enough for patients to have their genome sequenced before they receive genome-tailored treatments.

#23 Matt

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Posted 12 April 2005 - 02:45 PM

There was a chat with some one on a Sunday and the question was asked to him when he thinks this will become a reality for the average person. He said the next 30 years I think...

Looks like its gonna happen a lot sooner !

#24 kevin

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Posted 12 April 2005 - 02:55 PM

Link: http://www.eurekaler...--crh021805.php

Posted Image



California researchers help map human genetic variation across populations
New study makes whole-genome association studies possible

San Diego and Berkeley, CA, February 17, 2005 -- Computer scientists at two research centers affiliated with the University of California have teamed with biologists from Perlegen Sciences, Inc., to map key genetic signposts across three human populations. Their study – published in the Feb. 18 issue of Science – could make widely accessible the analysis of human variation based on whole-genome data, and speed efforts to pinpoint DNA variations that are associated with disease or with how patients respond differently to drugs.

"This project sets a new milestone in the search for genetic elements linked to complex genetic diseases such as Alzheimer's, cancer and multiple sclerosis," said co-author David R. Cox, Chief Scientific Officer at Mountain View, CA-based Perlegen. "Genome-wide analysis may soon become a standard methodology in the search for more effective, individualized treatments."

Researchers at Perlegen sequenced the single-letter variations (called single-nucleotide polymorphisms, or SNPs) in the DNA of 71 individuals of European American, African American, and Han Chinese American ancestry. Subsequently, scientists at the California Institute for Telecommunications and Information Technology (Calit2) at the University of California, San Diego, and the UC Berkeley-affiliated International Computer Science Institute (ICSI) helped analyze the set of over 100 million genotypes from the over 1.5 million SNPs sequenced in each sample by Perlegen.

"This is the first time that a SNP data set of that scale is being sequenced," said Eran Halperin, a research scientist at Berkeley-based ICSI. "For each of the 23 pairs of chromosomes in human DNA, the resulting data set consisted of 71 genotypes, which mix together the information from both copies of the chromosome. To see a clearer picture of a variation, we really want to know the variation on each chromosome, and we can do that by inferring haplotypes – the sequences of nucleotide bases in each copy of the chromosome."

Halperin and Calit2 researcher Eleazar Eskin, who co-authored the study with Perlegen scientists, have pioneered a method for translating genotypes into haplotypes, using the HAP software tool they co-developed For this study, the bioinformatics researchers had to process more than 190 million data points. "Using other programs, haplotyping would require at least a few months of CPU time," said Eskin, an assistant professor in Computer Science and Engineering at UC San Diego's Jacobs School of Engineering. "Using HAP on a regular laptop, this work would take only 200 CPU hours. But we were able to use a cluster of computers from Calit2's OptIPuter project, and that allowed us to perform our final entire analysis in less than 12 hours."

Until now, due to the high cost of sequencing technology, disease association studies have traditionally been performed over short genomic regions. The Science study indicates that genome-wide association studies will now be possible for a considerably reduced budget, as scientists build on the publicly-available data and tools made available by Perlegen, ICSI and Calit2.

The researchers in San Diego and Berkeley also used the HAP tool to partition the human genome into 'blocks', or regions, of limited diversity. These are regions where only a few common patterns account for the majority of the variation in the population. The resulting haplotype 'maps' across the three populations appeared qualitatively similar to the maps compiled by Perlegen using a different technique called 'linkage disequilibrium' (LD). LD involves correlations of DNA variants in physical proximity along a chromosome, and results from a combination of processes including mutation, natural selection, and genetic drift. Linkage disequilibrium is complex and varies from one region of the genome to another, as well as between different populations. According to the study, "LD maps and haplotype maps represent somewhat different aspects of the local structure of genetic variation."

"The partitioning of genomes into highly correlated regions may be extremely useful for geneticists worldwide," added ICSI's Halperin. "They could choose to sequence a small subset of SNPs in each region, and use the high correlations between the different SNPs in order to predict the SNPs that were not sequenced."

The HAP study found substantially more blocks in the African American map than in the European American and Han Chinese maps, indicating that the greatest genetic diversity was in samples of African American descent (a finding consistent with previous studies).

Other findings in the Science paper, titled "Whole Genome Patterns of Common DNA Variation in Three Diverse Human Populations," include:

Most functional human genetic variation is not population-specific;
The majority of the 1.58 million SNPs with high-quality genotypes were common in all three populations; and
"Private SNPs" – those SNPs segregating in only one population sample – were only 18% of the total.
Maps of the haplotype structure and the variants that are common in each region can be downloaded from the Calit2 HAP site, which is hosted by the National Biomedical Computational Resource at UCSD (see Related Links below). "We hope that researchers interested in specific regions of the genome will use this site to obtain information on the human variation in those regions," said Calit2 director Larry Smarr. "This is a great example of the revolution in computational biology and its potential benefits to society in the study of cardiovascular disease, mental illness and other conditions thought to result from a complex interplay of multiple genetic and environmental factors."

The SNPs analyzed in the Science study represent only a fraction of the more than 10 million common SNPs expected to exist in the human genome. But researchers at Perlegen developed a mathematical algorithm to identify so-called 'tag SNPs' that provide guideposts for finding common variants in the human genome. "This study and software tools mean that you no longer have to wait to do whole-genome association studies," said Perlegen scientist David A. Hinds, lead author on the study. "We've effectively figured out how to reduce the genotyping burden by identifying a reduced set of tag SNPs, thus decreasing the difficulty and cost of association studies. That said, even when reducing to tag SNPs, we still need to be able to genotype at least several hundred thousand SNPs to have a comprehensive whole-genome association study."

"This research provides a tool for exploring many questions remaining regarding the causal role of common human DNA variation in complex human traits and for investigating the nature of genetic variation within and between human populations," the Science paper concludes.

Perlegen is also cooperating with the public-sector International HapMap Project, which is expected to release more detailed descriptions of genetic variations later this year. "We see these two efforts as complementary," said Perlegen's Hinds. "The HapMap project will yield a denser map, with more SNPs across a deeper set of individuals." HapMap will describe variation across individuals of Japanese, Chinese, Nigerian and European ancestry.


###
About ICSI
The International Computer Science Institute (ICSI) is an independent, nonprofit research center affiliated with the University of California campus in Berkeley, California. Founded in 1986, ICSI provides a vibrant, international environment for approximately eighty scientists pursuing leading-edge research in networking, algorithms, bioinformatics, artificial intelligence, computational linguistics and spoken language processing. ICSI research is sponsored by a mix of government contracts, commercial partnerships and international visitor programs. www.icsi.berkeley.edu

About Calit2
The California Institute for Telecommunications and Information Technology (Calit2) is one of four California Institutes for Science and Innovation created in late 2000 by California to ensure that the state maintain its leadership in cutting-edge technologies and industries. Its mission: to extend the reach of the Internet throughout the physical world – enabling anywhere/anytime access to the Web. More than 200 faculty members from UC San Diego and UC Irvine are collaborating on interdisciplinary projects, with funding and other support from more than 50 industry partners. www.calit2.net

Note to Editors: The complete study in the Feb. 18 edition of Science is available online at http://www.sciencema...t/307/5712/1072.

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#25 kevin

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Posted 04 May 2005 - 01:35 AM

Link: http://www.fortune.c...1050124,00.html


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The Quest for Custom Cures
Boosted by new technology, the burgeoning science of genomics is ushering in an age of personalized medicine.
By John Simons, May 2, 2005

Edited by Bates, 23 July 2005 - 06:54 PM.


#26 kevin

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Posted 26 June 2005 - 06:08 PM

Link: http://www.chicagotr...ack=2&cset=true


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Genes: Your body's crystal ball
Genetic science is racing ahead toward a day when doctors will be able to predict what diseases you're susceptible to. But do you really want to know?

By Ronald Kotulak
Tribune science reporter
Published June 26, 2005


Doctors can now take a few of your cells, pull out the DNA, stretch it across a screen and diagnose more than 1,100 genetic defects that could mean trouble, ranging from rare disorders to more common ones like heart disease and cancer.

Surprising even the experts, genetic testing is racing ahead faster than doctors, genetic counselors and others can keep pace, driven by scientists eager to claim the prize of predicting diseases before they happen and perhaps preventing them.

The potential of the field raises questions for a public wary of peering into the genetic future and jaded by unfulfilled medical promises. How will people handle the news that ticking away in every cell of their body are potential disease genes inherited from their parents, which they in turn may have passed on to their children?

And everybody has them. Geneticists estimate that each person may have more than 30 genes that make them susceptible to a variety of disorders. A person's risk of developing a specific disease depends on which genetic combination he or she possesses in conjunction with environmental stressors arising from lifestyle choices or chemical exposure.

"Knowledge is a good thing when you can use it productively," said Dr. Wylie Burke, chief of medical history and ethics at the University of Washington. "But sometimes it's not a good thing. This whole genetic risk era is going to push us to think very carefully about that."

Many people are especially concerned about genetic discrimination--using abnormal genes to deny jobs or health insurance--and tests for genes that cause deadly illnesses for which there currently is no treatment, such as Huntington's disease.

A test for the Huntington's gene has been available for a decade, but it has been shunned by people at risk--children of parents with the disease--who don't want to live for years knowing the illness will start destroying their brain in midlife. And although an eight-year-old test can identify a gene associated with Alzheimer's disease, few physicians offer it to patients out of fear they might become despondent.

Still, some recent studies suggest people might be more willing to take the news in stride and act on it, especially if they are told the difference between a gene that causes a disease 100 percent of the time--as with Huntington's--and a gene that only increases their susceptibility, which is far more common.

Children of Alzheimer's patients whose genes were tested overwhelmingly accepted the genetic findings without becoming depressed or anxious, Dr. Robert C. Green of the Boston University School of Medicine reported last week at an Alzheimer's conference in Washington, D.C. [see this article which describes a study where knowledge of increased risk of Alzheimer's causes no increase in depression or anxiety among children of people with Alzheimer's]

Acting on genetic data

Those with the faulty gene also took steps to reduce their risk of contracting the disease, including exercising more, eating better, taking vitamins and engaging in mentally stimulating tasks, he said. "We found that learning you had a genetic risk marker made this more real to people and made them want to act on it," Green said.

Genetic testing was once mostly limited to newborns and people with single-gene disorders like Huntington's, but with the discovery in 1994 of two breast cancer genes, BRCA 1 and 2, the field rapidly expanded into the common adult killer diseases.

Between 1993 and 2004, gene tests jumped more than eleven-fold to 1,148, and the number of laboratories offering genetic testing increased more than fivefold to 577, according to the University of Washington's GeneTests Laboratory Directory, a federally supported agency that lists available genetic tests.

Genetic testing costs anywhere from a few hundred dollars to thousands per test. Many health insurance companies pay for them, depending on the type of coverage.

New era in medicine

Scientists are racing to discover disease-related genes because they promise to open a new era of predictive medicine, where each individual will eventually know the genes that increase his or her risk of illness, and what they can do to head off those health problems.

"In the next three or four years there's going to be an absolute outpouring of discoveries about gene variances that are associated with the risk of diabetes, heart disease, cancer, asthma, high blood pressure, mental illness and other conditions," said Dr. Francis Collins, director of the National Human Genome Research Institute.

"It will allow us to individualize programs of preventive medicine so that you could plan your own diet and lifestyle and medical surveillance based upon your genetic risks as opposed to some broad generic prescription of activities, which is what we currently do," he said.

"The argument against genetic testing was really, `Well, what are you going to do about it?'" said Dr. Olufunmilayo Olopade, director of the University of Chicago's Center for Clinical Cancer Genetics. "But I think cancer presents a unique opportunity for us because we know we can cure some cancers. We can prevent them."

Gene tests are available, for example, to diagnose people at risk of developing thyroid or colon cancer in their 30s or earlier. These cancers can be prevented through the removal of the thyroid or regular screening to remove polyps from the colon, Olopade said.

When Julie Spiekhout was diagnosed with breast cancer in August, she decided to have a genetic test and found she carries the BRCA 2 gene.

That information persuaded Spiekhout to have her ovaries removed, since the gene also increases the risk of ovarian cancer. The disease is difficult to diagnose early enough for a cure, and two of Spiekhout's aunts died of it.

Spiekhout, who is being treated at Northwestern Memorial Hospital, also plans to discuss the BRCA 2 gene with her 8-year-old daughter, sister and cousins so they can start mammograms early to detect breast cancer in its most curable stage or prevent it with drug therapy.

"Being diagnosed with cancer used to just be a death sentence," said Spiekhout, 39, of Highland, Ind. "Now, I never even thought that. My first thought was, what do I have to do to fight this? Give me the information I need and I'm going to do whatever I need to do."

Susceptibility genes, such as the BRCA genes and the one linked to Alzheimer's, indicate a level of risk rather than a foregone conclusion, Green said.

"They're sort of like finding out you have elevated cholesterol," he said. "It increases your chance of getting a disease, but it doesn't mean you're definitely going to get it."

People who have one copy of the Alzheimer's gene, ApoE4, are three to five times more likely to get the disease than people without it, Green said. Those with two copies are 20 to 30 times more likely to get it.

The study presented last week involved 162 people who had a parent with Alzheimer's disease. Half were told their genetic risk and the other half were not. A year later, there was no difference psychologically between the groups, Green said.

"Under carefully controlled circumstances, we are showing that people are handling information about susceptibility genes very well," Green said.

Yet considerable uncertainty remains about the public's willingness to accept genetic testing or how they will react.

`People react differently'

Dr. David Rubin, director of clinical education for gastroenterology at the U. of C., said some people at risk for a genetic disease grieve when told they don't have the gene. They suffer guilt at not being affected when other family members are.

"People react differently," said Kelly Ormand, director of the graduate program in genetic counseling at Northwestern University's Feinberg School of Medicine. "Some see genetic knowledge as valuable and that it gives you options and allows you time to prepare if you need to prepare for something like Alzheimer's disease.

"There are some people who just don't want to know," she said. "They believe it will make them anxious. `There's nothing I can do about it. What happens, happens.'"

Experts also are concerned that the rate of progress in discovering new disease genes is outpacing medicine's ability to use them to help patients.

"Some discoveries are so new we don't know how to use them yet in our practice," Rubin said. "You have a generation of physicians in practice who only learned simple genetics and haven't been able to keep up with some of the more complex advancements. [Sounds like they better get 'busy' then...-KP]

"It also takes time to gather a complete family history of disease and know what to do with it," he said. "Genetic counselors are in short supply and we're going to need more of them to help us understand how to interpret risk and what to do with it."

Federal law proposed

As genetic tests for common diseases become increasingly available, a backlash may build up if federal legislation is not passed to prohibit genetic discrimination, Collins said.

HIPPA, a federal law limiting access to medical records, provides genetic privacy for people with group health insurance. But for the growing number of people who have to obtain individual policies, there is no protection, he said.

A number of states, including Illinois, have passed anti-genetic discrimination laws, but they are usually too weak to provide adequate protection, Collins said. In February the U.S. Senate unanimously passed a bill that would ban discrimination against people because of their genes. But the proposed legislation has stalled in the House, Collins said, because of strong objections from the health insurance industry and the U.S. Chamber of Commerce.

"The promise of genetic testing, which has a great deal of potential to keep people healthy and treat disease more effectively, could end up just not happening because of people's fear that this kind of information will be used against them," he said.

Families can consider compiling their own information about family diseases.

Paula Cardinale of Hammond knew that a gene for colon cancer had been found in a second cousin, but two years ago, at age 29, she thought the disease was "an older person's problem."

Then a pain in her side led her to have a CT scan, which disclosed a large mass that turned out to be colon cancer. A blood test would reveal she had the mutated gene hMLH1 that leads to the development of colon polyps, which quickly turn cancerous, before age 30.

"It's been a huge relief for me," said Cardinale, who is being treated at the University of Chicago. "I feel like I have more control of a very scary situation. They have specific screening for me to go through to protect myself because early detection is lifesaving."

Cardinale, who now undergoes regular checks but is cancer free, knows her children, Gina, 4, and Joey, 2, have a 50 percent chance of having inherited the faulty gene.

"What this has taught me is how I'm going to raise my children to think of gene testing and screening," she said. "When you find something like that in your family, it should just be known simply as preventive maintenance to keep you healthy, like getting your teeth cleaned twice a year."

#27 kevin

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Posted 22 August 2005 - 05:32 AM

http://europa.eu.int...es/index_en.cfm


TECHNOLOGY, RESEARCH
Carry-on DNA – nanotech provides portable genetic risk detection

Everything from biomedicine to high-speed internet revolves around smaller, faster ways of doing things. Take, for example, miniature biosensing device based on micro- and nanotechnology that could process a patient’s DNA to give them a heads up on whether they are at risk of diseases, such as cancer. One EU project is putting the finishing touches on a system that will do just that.

Currently being developed by the EU-backed IST project OPTONANOGEN, a prototype of the system will initially be used to detect mutations of the BRCA1 gene responsible for between 2.5 and 5% of the incidences of breast cancer in women. The final system, however, could be used to detect virtually any genetic anomaly, as well as proteins linked to viruses, chemical contamination in food or water pollution, reports IST Results.

“There are a broad variety of applications for this system, although the main market is in biomedicine,” explains OPTONANOGEN coordinator Laura Lechuga at the National Microelectronics Centre (CNM) in Spain. Although commercial biosensing systems exist, they are bulkier and designed for use in laboratories. This Information Society Technologies project is the first to develop a fully integrated system on a smaller, more portable scale in this field, she notes.

The final device will be roughly the size of a human hand, allowing it to be used in doctors’ surgeries to determine the genetic predisposition of a patient to certain diseases in a matter of minutes. That compares to the hours or even days it can take to carry out the same analysis in a laboratory, which is generally only used to test high-risk groups, such as women with a family history of breast cancer.

Patented systems
To detect genetic mutations the OPTONANOGEN system uses an array of 20 microcantilevers coated in nucleic acid that react when they come into contact with a DNA sample, such as blood or other fluids, displaying the genetic anomaly. The sample is injected into the device via a microfluidic header and the deflection of the cantilevers – by as little as 0.1 to 0.5 nanometres – is picked up by a photo-detector array based on the reflection of light off the cantilevers from special laser technology, called Vertical Cavity Surface Emission Lasers.

“We’ve patented both the microcantilever set up and the optical detection system,” Lechuga says, “and we are due to take out a third patent on the microfluidic header, which is unique in that it uses individual inlet and outlet paths for each cantilever rather than one for the whole array.” This has never been achieved before, the scientist confirms.

The cantilever array and microfluidic header are due to be low-cost components that would be disposable if used for medical analysis but which could be cleansed and reused for other applications. After evaluation trials later this year, a commercial variant of the system is likely to be produced within two years by Sensia, a recently formed spin-off company from the CNM.

The IST programme is one of several priorities areas funded by the EU’s research Framework Programmes. Funding has also been set aside in the current programme (FP6), running from 2002-2006, for research into ‘Nanotechnologies and nano-sciences, knowledge-based multifunctional materials and new production processes and devices’, often abbreviated to NMP.

#28 kevin

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Posted 24 August 2005 - 03:17 AM

Link: http://www.newscient.../mg18725134.900


Glimpse your genetic future for $1000
20 August 2005
From New Scientist Print Edition. Subscribe and get 4 free issues.
Rowan Hooper


THE year is 2010. You walk into a lab in a shopping mall, pay $1000 and give a swab of skin cells from your cheek. A few days later you receive an email. It is a string of 3 billion DNA letters that hold the key to your future health.

That personal genome sequencing is within sight is remarkable. The first human genome sequence took $800 million and 11 years to complete. The "Sanger" method used to do it has changed little since it was developed in the 1970s by Fred Sanger at the University of Cambridge. Costs have come down, but sequencing large genomes is still the preserve of large, well-funded labs.

Now two groups have developed techniques that are already 100 times faster and are set to get faster and cheaper still. The new methods do away with the need for the bacteria used in the Sanger method. Instead they use picolitre-volume beads that contain a mix of the chemicals needed to amplify DNA letters or bases. These beads are so small that millions of them can be built into a single "chip", allowing huge amounts of DNA to be analysed at once.

Jonathan Rothberg, founder of 454 Life Sciences in Branford, Connecticut, and his team demonstrated their method by sequencing the 580,000-base genome of the bacterium Mycoplasma genitalum to an accuracy of 99.96 per cent in just four hours (Nature, DOI: 10.1038/nature03959).

Rothberg's 70-by-75-millimetre chip can sequence over 200,000 fragments simultaneously. The 454 method uses a version of a technique called pyrosequencing (see Diagram). First the genome to be sequenced is cut into fragments of around 100 bases. Each bead contains one fragment which is copied many times.

Primer sequences bind to the fragments and one of the four nucleotides (A, C, T or G) is added to the mix. If the nucleotide complements the base at the first position of the unknown fragment, it releases a pyrophosphate molecule that stimulates the firefly enzyme luciferase to generate a flash of light. The nucleotides are washed away and the cycle is repeated with the next nucleotide.
Posted Image

Cost will fall fast as we shrink our chips," says Rothberg. He is predicting that miniaturisation will follow a version of "Moore's law" - the rule of thumb that says computer chips halve in size every 18 months.
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At Harvard University, Gregory Porreca and his colleagues use a similar method, but at every stage four lengths of DNA are added, each nine bases long and with one of the four nucleotides at a known position. The nucleotides are labelled with fluorescent markers of different colours. If the nucleotide binds to the fragment DNA, it gives off a flash of light.

The Harvard method is cheaper because it uses off-the-shelf equipment, but is so far only able to "resequence" known genomes. So the method can be used to spot genetic variations that predispose a patient to cancer, for example, but it cannot be used to sequence unexplored genomes (Science, DOI: 10.1126/science.1117389).

Cheap sequencing will give individuals and their doctors the option of consulting their DNA. "The patient will then know what diseases he or she is genetically predisposed to and will be able to make proactive life choices to avert them," Porreca says. "The patient will also be able to receive treatment tailored to his or her own genetic make-up."

Both techniques have a great deal of potential, says Daniel Turner at the Wellcome Trust Sanger Institute in Cambridge, UK, one of the centres that sequenced the human genome. "The main limitation seems to be that the error rates of both methods are currently relatively high for individual reads."

#29 manofsan

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Posted 24 August 2005 - 04:35 AM

When I think of reading bits, CCDs reading optical flashes are only just one possibility. What about using magnetism, just like how a magnetic read head can read your hard drive data? As an altnerative to the luciferase light flashes, somebody's got to figure out a way for this DNA anti-sense binding to trigger a magnetic field which can be read by a magnetic read head. To me that will be more reliable and less error-prone than flashes of light.

To book this BIOSCIENCE ad spot and support Longecity (this will replace the google ad above) - click HERE.

#30 kevin

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Posted 24 August 2005 - 04:46 AM

If the H-bonding of the proof reading mechanism of polymerase could be duplicated it could be used to read out a sequence without having to use nucleotides at all... similar to your idea of reading a sequence magnetically..




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