Full genome sequencing - AbsoluteAstronomy.com

Full genome sequencing, also known as whole genome sequencing (WGS), complete genome sequencing, or entire genome sequencing, is a laboratory process that determines the complete DNA

DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

sequence of an organism's genome

Genome

In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

at a single time. This entails sequencing all of an organism's chromosomal DNA as well as DNA contained in the mitochondria

Mitochondrial DNA

Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...

and, for plants, in the chloroplast

Chloroplast

Chloroplasts are organelles found in plant cells and other eukaryotic organisms that conduct photosynthesis. Chloroplasts capture light energy to conserve free energy in the form of ATP and reduce NADP to NADPH through a complex set of processes called photosynthesis.Chloroplasts are green...

. Almost any biological sample—even a very small amount of DNA or ancient DNA

Ancient DNA

Ancient DNA is DNA isolated from ancient specimens. It can be also loosely described as any DNA recovered from biological samples that have not been preserved specifically for later DNA analyses...

—can provide the genetic material necessary for full genome sequencing. Such samples may include saliva

Saliva

Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...

, epithelial cells, bone marrow

Bone marrow

Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

, hair

Hair

Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....

(as long as the hair contains a hair follicle

Hair follicle

A hair follicle is a skin organ that produces hair. Hair production occurs in phases, including a growth phase , and cessation phase , and a rest phase . Stem cells are principally responsible for the production of hair....

), seed

Seed

A seed is a small embryonic plant enclosed in a covering called the seed coat, usually with some stored food. It is the product of the ripened ovule of gymnosperm and angiosperm plants which occurs after fertilization and some growth within the mother plant...

s, plant leaves, or anything else that has DNA-containing cells. Because the sequence data that is produced can be quite large (for example, there are approximately six billion base pair

Base pair

In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

s in each human diploid genome), genomic data is stored electronically and requires a large amount of computing power and storage capacity. Full genome sequencing would have been nearly impossible before the advent of the microprocessor

Microprocessor

A microprocessor incorporates the functions of a computer's central processing unit on a single integrated circuit, or at most a few integrated circuits. It is a multipurpose, programmable device that accepts digital data as input, processes it according to instructions stored in its memory, and...

, computers, and the Information Age

Information Age

The Information Age, also commonly known as the Computer Age or Digital Age, is an idea that the current age will be characterized by the ability of individuals to transfer information freely, and to have instant access to knowledge that would have been difficult or impossible to find previously...

.

Unlike full genome sequencing, DNA profiling only determines the likelihood that genetic material came from a particular individual or group; it does not contain additional information on genetic relationships, origin or susceptibility to specific diseases. Also unlike full genome sequencing, SNP genotyping

SNP genotyping

SNP genotyping is the measurement of genetic variations of single nucleotide polymorphisms between members of a species. It is a form of genotyping, which is the measurement of more general genetic variation. SNPs are one of the most common types of genetic variation...

covers less than 0.1% of the genome. Almost all truly complete genomes are of microbes; the term "full genome" is thus sometimes used loosely to mean "greater than 95%". The remainder of this article focuses on nearly complete human genomes.

In general, knowing the complete DNA sequence of an individual's genome does not, on its own, provide useful clinical information, but this may change over time as a large number of scientific studies continue to be published detailing clear associations between specific genetic variants and disease.

The first nearly complete human genomes sequenced were J. Craig Venter's (Caucasian

Caucasian race

The term Caucasian race has been used to denote the general physical type of some or all of the populations of Europe, North Africa, the Horn of Africa, Western Asia , Central Asia and South Asia...

at 7.5-fold average coverage), James Watson

James D. Watson

James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...

's (Caucasian male at 7.4-fold), a Han Chinese

Han Chinese

Han Chinese are an ethnic group native to China and are the largest single ethnic group in the world.Han Chinese constitute about 92% of the population of the People's Republic of China , 98% of the population of the Republic of China , 78% of the population of Singapore, and about 20% of the...

(YH at 36-fold), a Yoruba

Yoruba people

The Yoruba people are one of the largest ethnic groups in West Africa. The majority of the Yoruba speak the Yoruba language...

n from Nigeria

Nigeria

Nigeria , officially the Federal Republic of Nigeria, is a federal constitutional republic comprising 36 states and its Federal Capital Territory, Abuja. The country is located in West Africa and shares land borders with the Republic of Benin in the west, Chad and Cameroon in the east, and Niger in...

(at 30-fold), a female leukemia

Leukemia

Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

patient (at 33 and 14-fold coverage for tumor and normal tissues), and Seong-Jin Kim (Korean at 29-fold). There are currently over 60 nearly complete human genomes publicly available. Steve Jobs also had his genome sequenced for $100,000. Commercialization

Commercialization

Commercialization is the process or cycle of introducing a new product or production method into the market. The actual launch of a new product is the final stage of new product development, and the one where the most money will have to be spent for advertising, sales promotion, and other marketing...

of full genome sequencing is in an early stage and growing rapidly.

Early Techniques

Sequencing of nearly an entire human genome was first accomplished in 2000 partly through the use of shotgun sequencing

Shotgun sequencing

In genetics, shotgun sequencing, also known as shotgun cloning, is a method used for sequencing long DNA strands. It is named by analogy with the rapidly-expanding, quasi-random firing pattern of a shotgun....

technology. While full genome shotgun sequencing for small (4000–7000 base pair

Base pair

) genomes was already in use in 1979, broader application benefited from pairwise end sequencing, known colloquially as double-barrel shotgun sequencing. As sequencing projects began to take on longer and more complicated genomes, multiple groups began to realize that useful information could be obtained by sequencing both ends of a fragment of DNA. Although sequencing both ends of the same fragment and keeping track of the paired data was more cumbersome than sequencing a single end of two distinct fragments, the knowledge that the two sequences were oriented in opposite directions and were about the length of a fragment apart from each other was valuable in reconstructing the sequence of the original target fragment.

The first published description of the use of paired ends was in 1990 as part of the sequencing of the human HPRT

Hypoxanthine-guanine phosphoribosyltransferase

Hypoxanthine-guanine phosphoribosyltransferase is an enzyme encoded in humans by the HPRT1 gene.HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from...

locus, although the use of paired ends was limited to closing gaps after the application of a traditional shotgun sequencing approach. The first theoretical description of a pure pairwise end sequencing strategy, assuming fragments of constant length, was in 1991. In 1995 Roach et al. introduced the innovation of using fragments of varying sizes, and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets. The strategy was subsequently adopted by The Institute for Genomic Research

The Institute for Genomic Research

The Institute for Genomic Research was a non-profit genomics research institute founded in 1992 by Craig Venter in Rockville, Maryland, United States. It is now a part of the J. Craig Venter Institute.-History:...

(TIGR) to sequence the entire genome of the bacterium Haemophilus influenzae
Haemophilus influenzae
Haemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...

in 1995, and then by Celera Genomics

Celera Genomics

Celera Corporation was a business unit of the Applera Corporation, but was spun off in July 2008 to become an independent publicly traded company. In May 2011 Quest Diagnostics Incorporated completed the acquisition of Celera, which thus became a wholly owned subsidiary...

to sequence the entire fruit fly genome in 2000, and subsequently the entire human genome. Applied Biosystems

Applied Biosystems

Applied Biosystems, Inc. started as GeneCo , was the name of a pioneer biotechnology company founded in 1981 in Foster City, California, in the San Francisco Bay Area...

, now called Life Technologies

Life Technologies

Life Technologies is a global biotechnology company headquartered in Carlsbad, California. It possesses a portfolio of more than 9 million genetic research assays and custom solutions...

, manufactured the automated capillary sequencers utilized by both Celera Genomics and The Human Genome Project.

While capillary sequencing was the first approach to successfully sequence a nearly full human genome, it is still too expensive and takes too long for commercial purposes. Because of this, shotgun sequencing technology, even though it is still relatively 'new', since 2005 is being displaced by technologies like pyrosequencing

Pyrosequencing

Pyrosequencing is a method of DNA sequencing based on the "sequencing by synthesis" principle. It differs from Sanger sequencing, in that it relies on the detection of pyrophosphate release on nucleotide incorporation, rather than chain termination with dideoxynucleotides...

, SMRT sequencing, and nanopore technology.

Current Research

One possible way to accomplish the cost-effective high-throughput sequencing necessary to accomplish full genome sequencing is by using nanopore technology

Nanopore sequencing

Nanopore sequencing is a method under development since 1995 for determining the order in which nucleotides occur on a strand of DNA.A nanopore is simply a small hole, of the order of 1 nanometer in internal diameter...

, which is a patented technology held by Harvard University and Oxford Nanopore Technologies and licensed to biotechnology companies. To facilitate their full genome sequencing initiatives, Illumina

Illumina (company)

Illumina, Inc. is a company incorporated in April 1998 that develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function. Using its technologies, the company provides a line of products and services that serve the sequencing, genotyping and...

licensed nanopore sequencing technology from Oxford Nanopore Technologies and Sequenom

Sequenom

Sequenom is a manufacturer of DNA massarrays, based in San Diego, California, United States. The MassARRAY platform is used for SNP genotyping, methylation detection and quantitative gene expression analysis. Sequenom also manufactures clinical tests, such as SEQureDx, a noninvasive prenatal test...

licensed the technology from Harvard University. Another possible way to accomplish cost-effective high-throughput sequencing is by utilizing fluorophore

Fluorophore

A fluorophore, in analogy to a chromophore, is a component of a molecule which causes a molecule to be fluorescent. It is a functional group in a molecule which will absorb energy of a specific wavelength and re-emit energy at a different wavelength...

technology. Pacific Biosciences is currently using this approach in their SMRT (single molecule real time) DNA sequencing technology. Complete Genomics has developed DNA Nanoball

DNA nanoball sequencing

DNA nanoball sequencing is a high throughput sequencing technology that is used to determine the entire genomic sequence of an organism. The method uses rolling circle replication to amplify small fragments of genomic DNA into DNA nanoballs. Fluorescent probes bind to complementary DNA and the...

(DNB) technology that arranges DNA on self-assembling arrays. Complete Genomics’ sequencing technology combines its DNB arrays with its proprietary cPAL™ read technology. Pyrosequencing

Pyrosequencing

is a method of DNA sequencing

DNA sequencing

DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....

based on the sequencing by synthesis principle. The technique was developed by Pål Nyrén

Pål Nyrén

Pål Nyrén is a biochemistry professor at the Royal Institute of Technology , Stockholm. He is most famous for developing the pyrosequencing method for DNA sequencing.-Career:*1999 Professor in Biochemistry, KTH, Stockholm...

and his student Mostafa Ronaghi

Mostafa Ronaghi

Mostafa Ronaghi, born 1968. is a molecular biologist, specializing in DNA sequencing methodology . He earned his Ph.D. from the Royal Institute of Technology in Sweden in 1998.He is currently the Chief Technology Officer and Senior Vice President at Illumina...

at the Royal Institute of Technology

Royal Institute of Technology

The Royal Institute of Technology is a university in Stockholm, Sweden. KTH was founded in 1827 as Sweden's first polytechnic and is one of Scandinavia's largest institutions of higher education in technology. KTH accounts for one-third of Sweden’s technical research and engineering education...

in Stockholm in 1996, and is currently being used by 454 Life Sciences

454 Life Sciences

454 Life Sciences, is a biotechnology company based in Branford, Connecticut. It is a subsidiary of Roche, and specializes in high-throughput DNA sequencing.-History and Major Achievements:...

in their effort to deliver an affordable, fast and highly accurate full genome sequencing platform.

Commercialization

A number of public and private companies are competing to develop a full genome sequencing platform that is commercially robust for both research and clinical use, including Illumina

Illumina (company)

, Knome

Knome

Knome is an American personal genomics company that sells human whole genome and exome analysis and sequencing services to researchers and consumers...

, Sequenom

Sequenom

, 454 Life Sciences

454 Life Sciences

454 Life Sciences, is a biotechnology company based in Branford, Connecticut. It is a subsidiary of Roche, and specializes in high-throughput DNA sequencing.-History and Major Achievements:...

, Pacific Biosciences

Pacific Biosciences

Pacific Biosciences is a biotechnology company founded in 2004 that develops and manufactures systems for gene sequencing and some novel real time biological observation. They describe their platform as single molecule real time sequencing , based on the properties of zero-mode waveguides...

, Complete Genomics

Complete Genomics

Complete Genomics is a life sciences company that has developed and commercialized a DNA sequencing platform for human genome sequencing and analysis. This solution combines the company’s proprietary human genome sequencing technology with its informatics and data management software in an...

, Intelligent Bio-Systems, Genome Corp., ION Torrent Systems, Helicos Biosciences

Helicos Biosciences

Helicos BioSciences Corporation, is a publicly-traded life science company headquartered in Cambridge, Massachusetts focused on genetic analysis technologies for the research, drug discovery and diagnostic markets. The firm's Helicos Genetic Analysis Platform was the first DNA-sequencing...

, and BioNanomatrix. These companies are heavily financed and backed by venture capitalists, hedge funds, and investment banks.

Incentive

In October 2006, the X Prize Foundation

X Prize Foundation

The X PRIZE Foundation is a non-profit organization that designs and manages public competitions intended to encourage technological development that could benefit mankind....

, working in collaboration with the J. Craig Venter Science Foundation, established the Archon X Prize

Archon X Prize

The Archon X Prize for Genomics, the second X Prize to be offered by the X Prize Foundation, based in Santa Monica, California, was announced on October 4, 2006. The Archon X Prize in genomics is a joint effort of the X Prize Foundation and the J...

for Genomics, intending to award US$10 million to "the first Team that can build a device and use it to sequence 100 human genomes within 10 days or less, with an accuracy of no more than one error in every 100,000 bases sequenced, with sequences accurately covering at least 98% of the genome, and at a recurring cost of no more than US$10,000 per genome." An error rate of 1 in 100,000 bases, out of a total of six billion bases in the human diploid genome, would mean about 60,000 errors per genome. The error rates required for widespread clinical use, such as Predictive Medicine

Predictive medicine

Predictive medicine is a rapidly emerging field of medicine that entails predicting disease and instituting preventive measures in order to either prevent the disease altogether or significantly decrease its impact upon the patient...

is currently set by over 1,400 clinical single gene sequencing tests (for example, errors in BRCA1

BRCA1

BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...

gene for breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

risk analysis). As of December 2011, the Archon X Prize

Archon X Prize

for Genomics remains unclaimed.

2007

In 2007, Applied Biosystems

Applied Biosystems

Applied Biosystems, Inc. started as GeneCo , was the name of a pioneer biotechnology company founded in 1981 in Foster City, California, in the San Francisco Bay Area...

started selling a new type of sequencer called SOLiD System. The technology allowed users to sequence 60 gigabases per run.

2009

In early February 2009, Complete Genomics released a full sequence of a human genome that was sequenced using their service. The data indicates that Complete Genomics' full genome sequencing service accuracy is just under 99.999%, meaning that just one in every one hundred thousand variants was called incorrectly. This means that their full sequence of the human genome will contain approximately 80,000–100,000 false positive errors in each genome. However, this accuracy rate was based on Complete Genomics' sequence that was completed utilizing a 90× depth of coverage (each base in the genome was sequenced 90 times) while their commercialized sequence is reported to be only 40×. This accuracy rate may be acceptable for research purposes, and clinical use would require confirmation by other methods of any reportable alleles. Complete Genomics announced in Dec. 2010 that for the last 500 complete human genomes that it had sequenced, an average of over 98 percent of the genome was read at 10-fold or greater coverage. In addition, its software made high confidence calls of an average of over 95 percent of the genome and over 94 percent of the exome.

In March 2009, it was announced that Complete Genomics has signed a deal with the Broad Institute

Broad Institute

The Broad Institute is a genomic medicine research center located in Cambridge, Massachusetts, United States. Although it is independently governed and supported as a 501 nonprofit research organization, the institute is formally affiliated with the Massachusetts Institute of Technology, Harvard...

to sequence cancer patients' genomes and will be sequencing five full genomes to start. In April 2009, Complete Genomics announced that it plans to sequence 1,000 full genomes between June 2009 and the end of the year and that they plan to be able to sequence one million full genomes per year by 2013. Complete Genomics sequenced 50 genomes in 2009. Since then, it has significantly increased the throughout in its genome sequencing center and was able to sequence and analyze 300 complete human genomes in Q3 2010. Complete Genomics plans to officially launch in June 2009, although it is unknown if their lab will have received CLIA-certification by that time. Complete Genomics announced its R&D human genome sequencing service in October 2008 and its commercial sequencing service in May 2010. The company does not produce clinical data and as such its genome center does not require CLIA certification.

In June 2009, NABsys announced their goal of full genome sequencing for under US$100 per genome with a turnaround time of less than 15 minutes.

In June 2009, Illumina

Illumina (company)

announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30× for US$48,000 per genome. This is still expensive for widespread consumer use, but the price may decrease substantially over the next few years as they realize economies of scale and given the competition with other companies such as Complete Genomics. Jay Flatley, Illumina's President and CEO, stated that "during the next five years, perhaps markedly sooner," the price point for full genome sequencing will fall from US$48,000 to under US$1,000. Illumina has already signed agreements to supply full genome sequencing services to multiple direct-to-consumer personal genomics companies.

In August 2009, the founder of Helicos Biosciences, Dr. Stephen Quake, stated that using the company's Heliscope Single Molecule Sequencer he sequenced his own full genome for less than US$50,000. He stated that he expects the cost to decrease to the US$1,000 range within the next two to three years.

In August 2009, Pacific Biosciences secured an additional US$68 million in new financing, bringing their total capitalization to US$188 million. Pacific Biosciences said they are going to use this additional investment in order to prepare for the upcoming launch of their full genome sequencing service in 2010. Complete Genomics followed by securing another US$45 million in a fourth round venture funding during the same month. Complete Genomics has also made the claim that it will sequence 10,000 full genomes by the end of 2010. Since then, it has significantly increased the throughout in its genome sequencing center and was able to sequence and analyze 300 complete human genomes in Q3 2010.

GE Global Research

GE Global Research

GE Global Research is the research and development division of General Electric.GE Global Research's primary facility is located in Niskayuna, New York. The Advanced Manufacturing and Software Technology Center is a satelite facility located in Van Buren, Michigan...

is also part of this race to commercialize full genome sequencing as they have been working on creating a service that will deliver a full genome for US$1,000 or less.

In September 2009, the President of Halcyon Molecular announced that they will be able to provide full genome sequencing in under 10 minutes for less than US$100 per genome. This is, to date, the most ambitious promise of any full genome sequencing company.

In October 2009, IBM

IBM

International Business Machines Corporation or IBM is an American multinational technology and consulting corporation headquartered in Armonk, New York, United States. IBM manufactures and sells computer hardware and software, and it offers infrastructure, hosting and consulting services in areas...

announced that they were also in the heated race to provide full genome sequencing for under US$1,000, with their ultimate goal being able to provide their service for US$100 per genome. IBM's full genome sequencing technology, which uses nanopores, is known as the "DNA Transistor".

In November 2009, Complete Genomics published a peer-reviewed paper in Science demonstrating its ability to sequence a complete human genome for US$1,700. If true, this would mean the cost of full genome sequencing has come down exponentially within just a single year from around US$100,000 to US$50,000 and now to US$1,700. This consumables cost was clearly detailed in the Science paper. However, Complete Genomics has previously released statements that it was unable to follow through on. For example, the company stated it would officially launch and release its service during the "summer of 2009", provide a "US$5,000" full genome sequencing service by the "summer of 2009", and "sequence 1,000 genomes between June 2009 and the end of 2009" – all of which, as of November 2009, have not yet occurred. Complete Genomics launched its R&D human genome sequencing service in October 2008 and its commercial service in May 2010. The company sequenced 50 genomes in 2009. Since then, it has significantly increased the throughput of its genome sequencing factory and was able to sequence and analyze 300 genomes in Q3 2010.

Also in November 2009, Complete Genomics announced that it was beginning a large-scale human genome sequencing study of Huntington’s disease (up to 100 genomes) with the Institute for Systems Biology.

2010

In March 2010 Researchers from the Medical College of Wisconsin announced the first successful use of Genome Wide sequencing to change the treatment of a patient. This story was later retold in a pulitzer prize winning article and touted as a significant accomplishment in Nature and by the director of the NIH in presentations at congress.

In March 2010, Pacific Biosciences said they have raised more than US$256 million in venture capital money and that they will be shipping their first ten full genome sequencing machines by the end of 2010. The company reported that the market initially will be researchers and academic institutions and then will rapidly turn into clinical applications that will be applicable to every single person in the world. Pacific Biosciences also stated that their second-generation machine, which is scheduled for release in 2015, will be capable of providing a full genome sequence for a person in just 15 minutes for less than US$100. Several other technologies have similar goals. Meanwhile, full genome sequencing might revolutionize medicine at even current prices by providing a clinician with a full genome for each one of his or her patients. However, some critics have stated that even if they are supplied with a full genome sequence of a patient, they would not know how to analyze or make use of that data. Since then, new resources have begun to address this.

Also in March 2010, Complete Genomics’ customers began publishing papers describing research breakthroughs that they have made using data it has provided. Examples included the Institute for Systems Biology’s project to sequence a family of four and verify the gene responsible for Miller Syndrome, a rare craniofacial disorder[x] and Genentech’s work to sequence and compare a patient’s primary lung tumor and adjacent normal tissue[y].

In June 2010, Illumina lowered the cost of its individual sequencing service to US$19,500 from US$48,000. The company is offering a discounted price of US$9,500 for people with serious medical conditions who could potentially benefit from having their genomes decoded.

2011

Knome

Knome is an American personal genomics company that sells human whole genome and exome analysis and sequencing services to researchers and consumers...

provides full genome (98% genome) sequencing services for US$39,500 for whole genome sequencing and interpretation for consumers. It's US$29,500 for whole genome sequencing and analysis for researchers depending on their requirements.

Complete Genomics charges approximately US$10,000 to sequence a complete human genome and offers discounts for large orders. This service includes sample quality control, library preparation, sequencing, mapping, assembly and data analysis.

In May 2011, Illumina announced that it had lowered its Full Genome Sequencing service to US$5,000 per human genome and US$4,000 per genome for bulk orders of 50 or more.

Helicos Biosciences, Pacific Biosciences, Complete Genomics, Illumina, Sequenom, ION Torrent Systems, Halcyon Molecular, NABsys, IBM, and GE Global appear to all be going head to head in the race to commercialize full genome sequencing.

Disruptive technology

Full genome sequencing provides information on a genome that is orders of magnitude larger than that provided by the current leader in genotyping technology, DNA arrays. For humans, DNA arrays currently provide genotypic information on up to one million genetic variants, while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000 times more data. Because of this, full genome sequencing is considered disruptive

Disruptive technology

A disruptive technology or disruptive innovation is an innovation that helps create a new market and value network, and eventually goes on to disrupt an existing market and value network , displacing an earlier technology there...

to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their consumables cost of US$5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays (US$500 per 1 million basepairs). Agilent, another established DNA array manufacturer, is working on targeted (selective region) genome sequencing technologies. It is thought that Affymetrix

Affymetrix

Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...

, the pioneer of array technology in the 1990s, has fallen behind due to significant corporate and stock turbulence and is currently not working on any known full genome sequencing approach. It is unknown what will happen to the DNA array market once full genome sequencing becomes commercially widespread, especially as companies and laboratories providing this disruptive technology start to realize economies of scale

Economies of scale

Economies of scale, in microeconomics, refers to the cost advantages that an enterprise obtains due to expansion. There are factors that cause a producer’s average cost per unit to fall as the scale of output is increased. "Economies of scale" is a long run concept and refers to reductions in unit...

. It is postulated, however, that this new technology may significantly diminish the total market size for arrays and any other sequencing technology once it becomes commonplace for individuals and newborns to have their full genomes sequenced.

Sequencing versus analysis

Full genome sequencing provides raw data on all six billion letters in an individual's DNA. However, it does not provide an analysis of what that data means or how that data can be utilized in various clinical applications, such as in medicine to help prevent disease. As of 2010 the companies that are working on providing full genome sequencing provide clinical CLIA certified data (Illumina) and analytical services for the interpretation of the full genome data (Knome) With only one instition offering sequencing and analysis in a clinical setting. Nevertheless there is plenty of room for researchers or companies to improve such analyses and make it useful to physicians and patients.

Societal impact

Inexpensive, time-efficient full genome sequencing will be a major accomplishment not only for the field of Genomics

Genomics

Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...

, but for the entire human civilization

Civilization

Civilization is a sometimes controversial term that has been used in several related ways. Primarily, the term has been used to refer to the material and instrumental side of human cultures that are complex in terms of technology, science, and division of labor. Such civilizations are generally...

because, for the first time, individuals will be able to have their entire genome sequenced. Utilizing this information, it is speculated that health care professionals, such as physicians and genetic counselors, will eventually be able to use genomic information to predict what diseases a person may get in the future and attempt to either minimize the impact of that disease or avoid it altogether through the implementation of personalized, preventive medicine

Preventive medicine

Preventive medicine or preventive care refers to measures taken to prevent diseases, rather than curing them or treating their symptoms...

. Full genome sequencing will allow health care professionals to analyze the entire human genome of an individual and therefore detect all disease-related genetic variants, regardless of the genetic variant's prevalence or frequency. This will enable the rapidly emerging medical fields of Predictive Medicine

Predictive medicine

and Personalized Medicine

Personalized medicine

Personalized medicine is a medical model emphasizing in general the customization of healthcare, with all decisions and practices being tailored to individual patients in whatever ways possible...

and will mark a significant leap forward for the clinical genetic revolution. Full genome sequencing is clearly of great importance for research into the basis of genetic disease and has shown significant benefit to a subset of individuals with rare disease in the clinical setting .
Illumina's CEO, Jay Flatley, stated in February 2009 that "A complete DNA read-out for every newborn will be technically feasible and affordable in less than five years, promising a revolution in healthcare" and that "by 2019 it will have become routine to map infants' genes when they are born." This potential use of genome sequencing is highly controversial, as it runs counter to established ethical

Ethics

Ethics, also known as moral philosophy, is a branch of philosophy that addresses questions about morality—that is, concepts such as good and evil, right and wrong, virtue and vice, justice and crime, etc.Major branches of ethics include:...

norms for predictive genetic testing

Genetic testing

Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...

of asymptomatic minors that have been well established in the fields of medical genetics

Medical genetics

Medical genetics is the specialty of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics differs from Human genetics in that human genetics is a field of scientific research that may or may not apply to medicine, but medical genetics refers to the...

and genetic counseling

Genetic counseling

Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...

. The traditional guidelines for genetic testing have been developed over the course of several decades since it first became possible to test for genetic markers associated with disease, prior to the advent of cost-effective, comprehensive genetic screening. It is established that norms

Norm (sociology)

Social norms are the accepted behaviors within a society or group. This sociological and social psychological term has been defined as "the rules that a group uses for appropriate and inappropriate values, beliefs, attitudes and behaviors. These rules may be explicit or implicit...

, such as in the sciences and the field of genetics, are subject to change and evolve over time. It is unknown whether traditional norms practiced in medical genetics today will be altered by new technological advancements such as full genome sequencing.

Today, parents have the legal authority to obtain testing of any kind for their children. Currently available newborn screening

Newborn screening

Newborn screening is the process by which infants are screened shortly after birth for a list of disorders that are treatable, but difficult or impossible to detect clinically. Screening programs are often run by state or national governing bodies with the goal of screening all infants born in the...

for childhood diseases allows detection of rare disorders that can be prevented or better treated by early detection and intervention. Specific genetic tests

Genetic testing

are also available to determine an etiology when a child's symptoms appear to have a genetic basis. Full genome sequencing, in addition has the potential to reveal a large amount of information (such as carrier status

Genetic carrier

A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...

for autosomal recessive disorders, genetic risk factors for complex adult-onset diseases, and other predictive medical and non-medical information) that is currently not completely understood, may not be clinically useful to the child during childhood, and may not necessarily be wanted by the individual upon reaching adulthood. Despite the benefits of predicting disease risk in childhood, genetic testing also introduces potential harms (such as discovery of non-paternity

Non-paternity event

Non-paternity event is a term in genetic genealogy and clinical genetics to describe the case where the biological father of a child is someone other than who it is presumed to be. The presumption may be either on the part of the presumed father or by the physician...

, genetic discrimination

Genetic discrimination

Genetic discrimination occurs when people are treated differently by their employer or insurance company because they have a gene mutation that causes or increases the risk of an inherited disorder. People who undergo genetic testing may be at risk for genetic discrimination.The results of a...

, and psychological impacts). The established ethical guidelines for predictive genetic testing of asymptomatic minors thus has more to do with protecting this vulnerable population and preserving the individual's privacy

Privacy

Privacy is the ability of an individual or group to seclude themselves or information about themselves and thereby reveal themselves selectively...

and autonomy

Autonomy

Autonomy is a concept found in moral, political and bioethical philosophy. Within these contexts, it is the capacity of a rational individual to make an informed, un-coerced decision...

to know or not to know their genetic information, than with the technology that makes this possible. While parents may have legal authority to obtain such testing, the mainstream opinion of professional medical genetics societies is that presymptomatic testing should be offered to minors only when they are competent to understand the relevancy of genetic screening so as to allow them to participate in the decision about whether or not it is appropriate for them.

External links

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Early Techniques

Current Research

Commercialization

Incentive

2007

2009

2010

2011

Disruptive technology

Sequencing versus analysis

Societal impact

See also

External links