Difference between revisions of "Full Genome Sequencing"

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<p><strong>Full genome sequencing (FGS)</strong>, also known as <strong>whole genome sequencing</strong>, <strong>complete genome sequencing</strong>, or <strong>entire genome sequencing</strong>, is a laboratory process that determines the complete <font color="#0066cc">DNA</font> sequence of an organism's <font color="#0066cc">genome</font> at a single time. This entails sequencing all of an organism's <font color="#0066cc">chromosomal</font> DNA as well as DNA contained in the <font color="#0066cc">mitochondria</font> or <font color="#0066cc">chloroplast</font>, depending respectively on whether the organism is an animal or plant. Almost any biological sample&mdash;even a very small amount of DNA or <font color="#0066cc">ancient DNA</font>&mdash;can provide the genetic material necessary for full genome sequencing. Such samples may include saliva, <font color="#0066cc">epithelial cells</font>, <font color="#0066cc">bone marrow</font>, hair (as long as the hair contains a <font color="#0066cc">hair follicle</font>), seeds, 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 <font color="#0066cc">base pairs</font> 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 <font color="#0066cc">microprocessor</font>, <font color="#0066cc">computers</font>, and the <font color="#0066cc">Information Age</font>.</p>
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<p><span style="font-size: small; "><strong>Full genome <font color="#000000">sequencing (FGS)</font></strong><font color="#000000">, also known as <strong>whole genome sequencing</strong>, <strong>complete genome sequencing</strong>, or <strong>entire genome sequencing</strong>, is a laboratory process that determines the complete DNA sequence of an organism's genome at a single time. </font></span></p>
<p>Full genome sequencing should thus not be confused with <font color="#0066cc">DNA profiling</font>. The latter only determines the likelihood that genetic material came from a particular individual or group and does not contain additional information on genetic relationships, origin or suspectability on specific diseases. <sup id="cite_ref-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>1<span>]</span></font></font></sup>. It is also distinct from <font color="#0066cc">SNP genotyping</font> which covers less than 0.1% of the genome. Almost all truly complete genomes are of microbes, the term &quot;full genome&quot; is sometimes used loosely to mean &quot;greater than 95%&quot;. The remainder of this article focuses on nearly complete human genomes.</p>
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<p><span style="font-size: small; "><font color="#000000">This entails sequencing all of an organism's chromosomal DNA as well as DNA contained in the mitochondria or chloroplast, depending respectively on whether the organism is an animal or plant. Almost any biological sample&mdash;even a very small amount of DNA or ancient DNA&mdash;can provide the genetic material necessary for full genome sequencing. Such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, 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 pairs 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, computers, and the Information Age.</font></span></p>
<p>Full genome sequencing only refers to the laboratory process of deducing a person's entire genetic code and, on its own, may not contain any clinical assessment or useful clinical information. However, 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.<sup id="cite_ref-pmid17554300_1-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>2<span>]</span></font></font></sup><sup id="cite_ref-pmid17898773_2-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>3<span>]</span></font></font></sup></p>
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<p><span style="font-size: small; "><font color="#000000">Full genome sequencing should thus not be confused with DNA profiling. The latter only determines the likelihood that genetic material came from a particular individual or group and does not contain additional information on genetic relationships, origin or suspectability on specific diseases. <sup id="cite_ref-0" class="reference">[1]</sup>. It is also distinct from SNP genotyping which covers less than 0.1% of the genome. Almost all truly complete genomes are of microbes, the term &quot;full genome&quot; is sometimes used loosely to mean &quot;greater than 95%&quot;. The remainder of this article focuses on nearly complete human genomes.</font></span></p>
<p>The first nearly complete human genomes sequenced were <font color="#0066cc">J. Craig Venter</font>'s (caucasian male at 7.5-fold average coverage) <sup id="cite_ref-3" class="reference"><font size="2"><font color="#0066cc"><span>[</span>4<span>]</span></font></font></sup><sup id="cite_ref-4" class="reference"><font size="2"><font color="#0066cc"><span>[</span>5<span>]</span></font></font></sup><sup id="cite_ref-pmid17803354_5-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>6<span>]</span></font></font></sup> and <font color="#0066cc">James Watson</font>'s (caucasian male at 7.4-fold).<sup id="cite_ref-6" class="reference"><font size="2"><font color="#0066cc"><span>[</span>7<span>]</span></font></font></sup><sup id="cite_ref-7" class="reference"><font size="2"><font color="#0066cc"><span>[</span>8<span>]</span></font></font></sup><sup id="cite_ref-8" class="reference"><font size="2"><font color="#0066cc"><span>[</span>9<span>]</span></font></font></sup>, a Han Chinese (YH at 36-fold) <sup id="cite_ref-9" class="reference"><font size="2"><font color="#0066cc"><span>[</span>10<span>]</span></font></font></sup>, a Yoruban from Nigeria (at 30-fold) <sup id="cite_ref-10" class="reference"><font size="2"><font color="#0066cc"><span>[</span>11<span>]</span></font></font></sup>, a female leukemia patient (at 33 and 14-fold coverage for tumor and normal tissues)<sup id="cite_ref-11" class="reference"><font size="2"><font color="#0066cc"><span>[</span>12<span>]</span></font></font></sup>, and Seong-Jin Kim (Korean at 29-fold) <sup id="cite_ref-12" class="reference"><font size="2"><font color="#0066cc"><span>[</span>13<span>]</span></font></font></sup>. Other full genomes have been sequenced but not published, and as of June 2009, <font color="#0066cc">commercialization</font> of full genome sequencing is in an early stage and growing rapidly.</p>
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<p><font color="#000000">Full genome sequencing only refers to the laboratory process of deducing a person's entire genetic code and, on its own, may not contain any clinical assessment or useful clinical information. However, 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.<sup id="cite_ref-pmid17554300_1-0" class="reference">[2]</sup><sup id="cite_ref-pmid17898773_2-0" class="reference">[3]</sup></font></p>
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<p><span style="font-size: small; "><font color="#000000">The first nearly complete human genomes sequenced were J. Craig Venter's (caucasian male at 7.5-fold average coverage) <sup id="cite_ref-3" class="reference">[4]</sup><sup id="cite_ref-4" class="reference">[5]</sup><sup id="cite_ref-pmid17803354_5-0" class="reference">[6]</sup> and James Watson's (caucasian male at 7.4-fold).<sup id="cite_ref-6" class="reference">[7]</sup><sup id="cite_ref-7" class="reference">[8]</sup><sup id="cite_ref-8" class="reference">[9]</sup>, a Han Chinese (YH at 36-fold) <sup id="cite_ref-9" class="reference">[10]</sup>, a Yoruban from Nigeria (at 30-fold) <sup id="cite_ref-10" class="reference">[11]</sup>, a female leukemia patient (at 33 and 14-fold coverage for tumor and normal tissues)<sup id="cite_ref-11" class="reference">[12]</sup>, and Seong-Jin Kim (Korean at 29-fold) <sup id="cite_ref-12" class="reference">[13]</sup>. Other full genomes have been sequenced but not published, and as of June 2009, commercialization of full genome sequencing is in an early stage and growing rapidly.</font></span></p>
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<p><b><span style="font-size: medium; ">[[Genome Sequencing Procedure]]</span></b></p>
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<h2><span class="mw-headline">New techniques</span></h2>
 
<h2><span class="mw-headline">New techniques</span></h2>
 
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An ABI PRISM 3100 Genetic Analyzer. Sequencers automate the process of sequencing the genome.</div>
 
An ABI PRISM 3100 Genetic Analyzer. Sequencers automate the process of sequencing the genome.</div>
 
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<p>One possible way to accomplish the cost-effective <font color="#0066cc">high-throughput sequencing</font> necessary to accomplish full genome sequencing is by using <font color="#0066cc">Nanopore</font> technology, which is a patented technology held by Harvard University and <font color="#0066cc">Oxford Nanopore Technologies</font> and licensed to biotechnology companies.<sup id="cite_ref-13" class="reference"><font size="2"><font color="#0066cc"><span>[</span>14<span>]</span></font></font></sup> To facilitate their full genome sequencing initiatives, <font color="#0066cc">Illumina</font> licensed nanopore sequencing technology from <font color="#0066cc">Oxford Nanopore Technologies</font> and <font color="#0066cc">Sequenom</font> licensed the technology from Harvard University.<sup id="cite_ref-14" class="reference"><font size="2"><font color="#0066cc"><span>[</span>15<span>]</span></font></font></sup><sup id="cite_ref-15" class="reference"><font size="2"><font color="#0066cc"><span>[</span>16<span>]</span></font></font></sup> Another possible way to accomplish cost-effective high-throughput sequencing is by utilizing <font color="#0066cc">fluorophore</font> technology. Pacific Biosciences is currently using this approach in their SMRT (single molecule real time) DNA sequencing technology.<sup id="cite_ref-16" class="reference"><font size="2"><font color="#0066cc"><span>[</span>17<span>]</span></font></font></sup> Complete Genomics is developing DNA Nanoball (DNB) technology that are arranged on self-assembling arrays.<sup id="cite_ref-17" class="reference"><font size="2"><font color="#0066cc"><span>[</span>18<span>]</span></font></font></sup> <font color="#0066cc">Pyrosequencing</font> is a method of <font color="#0066cc">DNA sequencing</font> based on the sequencing by synthesis principle.<sup id="cite_ref-18" class="reference"><font size="2"><font color="#0066cc"><span>[</span>19<span>]</span></font></font></sup> The technique was developed by <font color="#0066cc">P&aring;l Nyr&eacute;n</font> and his student <font color="#0066cc">Mostafa Ronaghi</font> at the <font color="#0066cc">Royal Institute of Technology</font> in Stockholm in 1996,<sup id="cite_ref-RonachiScience_19-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>20<span>]</span></font></font></sup><sup id="cite_ref-pmid8923969_20-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>21<span>]</span></font></font></sup><sup id="cite_ref-pmid17185753_21-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>22<span>]</span></font></font></sup> and is currently being used by <font color="#0066cc">454 Life Sciences</font> in their effort to deliver an affordable, fast and highly accurate full genome sequencing platform.<sup id="cite_ref-22" class="reference"><font size="2"><font color="#0066cc"><span>[</span>23<span>]</span></font></font></sup></p>
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<p><font color="#000000">One possible way to accomplish the cost-effective high-throughput sequencing necessary to accomplish full genome sequencing is by using Nanopore technology, which is a patented technology held by Harvard University and Oxford Nanopore Technologies and licensed to biotechnology companies.<sup id="cite_ref-13" class="reference"><font size="2"><span>[</span>14<span>]</span></font></sup> To facilitate their full genome sequencing initiatives, Illumina licensed nanopore sequencing technology from Oxford Nanopore Technologies and Sequenom licensed the technology from Harvard University.<sup id="cite_ref-14" class="reference"><font size="2"><span>[</span>15<span>]</span></font></sup><sup id="cite_ref-15" class="reference"><font size="2"><span>[</span>16<span>]</span></font></sup> Another possible way to accomplish cost-effective high-throughput sequencing is by utilizing fluorophore technology. Pacific Biosciences is currently using this approach in their SMRT (single molecule real time) DNA sequencing technology.<sup id="cite_ref-16" class="reference"><font size="2"><span>[</span>17<span>]</span></font></sup> Complete Genomics is developing DNA Nanoball (DNB) technology that are arranged on self-assembling arrays.<sup id="cite_ref-17" class="reference"><font size="2"><span>[</span>18<span>]</span></font></sup> Pyrosequencing is a method of DNA sequencing based on the sequencing by synthesis principle.<sup id="cite_ref-18" class="reference"><font size="2"><span>[</span>19<span>]</span></font></sup> The technique was developed by P&aring;l Nyr&eacute;n and his student Mostafa Ronaghi at the Royal Institute of Technology in Stockholm in 1996,<sup id="cite_ref-RonachiScience_19-0" class="reference"><font size="2"><span>[</span>20<span>]</span></font></sup><sup id="cite_ref-pmid8923969_20-0" class="reference"><font size="2"><span>[</span>21<span>]</span></font></sup><sup id="cite_ref-pmid17185753_21-0" class="reference"><font size="2"><span>[</span>22<span>]</span></font></sup> and is currently being used by 454 Life Sciences in their effort to deliver an affordable, fast and highly accurate full genome sequencing platform.<sup id="cite_ref-22" class="reference"><font size="2"><span>[</span>23<span>]</span></font></sup></font></p>
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<h2><span class="mw-headline">Older techniques</span></h2>
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<h2><span class="mw-headline"><font color="#000000">Older techniques</font></span></h2>
<p>Full genome sequencing of the entire human genome was first accomplished in 2000 partly through the use of <font color="#0066cc">shotgun sequencing</font> technology. While full genome shotgun sequencing for small (4000&ndash;7000 <font color="#0066cc">base pair</font>) genomes was already in use in 1979,<sup id="cite_ref-pmid461197_23-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>24<span>]</span></font></font></sup> broader application benefited from pairwise end sequencing, known colloquially as <em>double-barrel shotgun sequencing</em>. 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.</p>
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<p><font color="#000000">Full genome sequencing of the entire human genome was first accomplished in 2000 partly through the use of shotgun sequencing technology. While full genome shotgun sequencing for small (4000&ndash;7000 base pair) genomes was already in use in 1979,<sup id="cite_ref-pmid461197_23-0" class="reference"><font size="2"><span>[</span>24<span>]</span></font></sup> broader application benefited from pairwise end sequencing, known colloquially as <em>double-barrel shotgun sequencing</em>. 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.</font></p>
<p>The first published description of the use of paired ends was in 1990 as part of the sequencing of the human <font color="#0066cc">HPRT</font> locus,<sup id="cite_ref-24" class="reference"><font size="2"><font color="#0066cc"><span>[</span>25<span>]</span></font></font></sup> 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.<sup id="cite_ref-pmid2341149_25-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>26<span>]</span></font></font></sup> In 1995 Roach et al.introduced the innovation of using fragments of varying sizes,<sup id="cite_ref-pmid7601461_26-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>27<span>]</span></font></font></sup> and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets. The strategy was subsequently adopted by <font color="#0066cc">The Institute for Genomic Research</font> (TIGR) to sequence the entire genome of the bacterium <em><font color="#0066cc">Haemophilus influenzae</font></em> in 1995,<sup id="cite_ref-pmid7542800_27-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>28<span>]</span></font></font></sup> and then by <font color="#0066cc">Celera Genomics</font> to sequence the entire fruit fly genome in 2000,<sup id="cite_ref-28" class="reference"><font size="2"><font color="#0066cc"><span>[</span>29<span>]</span></font></font></sup> and subsequently the entire human genome. <font color="#0066cc">Applied Biosystems</font>, now called <font color="#0066cc">Life Technologies</font>, manufactured the shotgun sequencers utilized by both Celera Genomics and The Human Genome Project.</p>
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<p><font color="#000000">The first published description of the use of paired ends was in 1990 as part of the sequencing of the human HPRT locus,<sup id="cite_ref-24" class="reference"><font size="2"><span>[</span>25<span>]</span></font></sup> 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.<sup id="cite_ref-pmid2341149_25-0" class="reference"><font size="2"><span>[</span>26<span>]</span></font></sup> In 1995 Roach et al.introduced the innovation of using fragments of varying sizes,<sup id="cite_ref-pmid7601461_26-0" class="reference"><font size="2"><span>[</span>27<span>]</span></font></sup> 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 (TIGR) to sequence the entire genome of the bacterium <em>Haemophilus influenzae</em> in 1995,<sup id="cite_ref-pmid7542800_27-0" class="reference"><font size="2"><span>[</span>28<span>]</span></font></sup> and then by Celera Genomics to sequence the entire fruit fly genome in 2000,<sup id="cite_ref-28" class="reference"><font size="2"><span>[</span>29<span>]</span></font></sup> and subsequently the entire human genome. Applied Biosystems, now called Life Technologies, manufactured the shotgun sequencers utilized by both Celera Genomics and The Human Genome Project.</font></p>
<p>While shotgun sequencing was one of the first approaches utilized to successfully sequence the full genome of a human, it is too expensive and requires too long of a turn-around-time to be utilized for commercial purposes. Because of this, shotgun sequencing technology, even though it is still relatively 'new', is being displaced by technologies like pyrosequencing, SMRT sequencing, and nanopore technology.<sup id="cite_ref-pmid19193124_29-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>30<span>]</span></font></font></sup></p>
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<p><font color="#000000">While shotgun sequencing was one of the first approaches utilized to successfully sequence the full genome of a human, it is too expensive and requires too long of a turn-around-time to be utilized for commercial purposes. Because of this, shotgun sequencing technology, even though it is still relatively 'new', is being displaced by technologies like pyrosequencing, SMRT sequencing, and nanopore technology.<sup id="cite_ref-pmid19193124_29-0" class="reference"><font size="2"><span>[</span>30<span>]</span></font></sup></font></p>
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<h2><span class="mw-headline">Race to commercialization</span></h2>
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<p>In October 2006, the <font color="#0066cc">X Prize Foundation</font>, working in collaboration with the J. Craig Venter Science Foundation, established the <font color="#0066cc">Archon X Prize</font> for Genomics,<sup id="cite_ref-30" class="reference"><font size="2"><font color="#0066cc"><span>[</span>31<span>]</span></font></font></sup> intending to award <font color="#0066cc">US$</font>10&nbsp;million to &quot;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 $10,000&nbsp;per genome.&quot;<sup id="cite_ref-31" class="reference"><font size="2"><font color="#0066cc"><span>[</span>32<span>]</span></font></font></sup> However, higher accuracy rates (or confirmatory methods) are desirable for some clinical applications. An error rate of 1&nbsp;in 100,000&nbsp;bases, out of a total of six billion bases in the human diploid genome, would mean about 60,000&nbsp;errors per genome, which is a significant number of false positives and negatives. For the latter it is not known where the errors occur . The error rates required for widespread clinical use, such as <font color="#0066cc">Predictive Medicine</font><sup id="cite_ref-pmid17055251_32-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>33<span>]</span></font></font></sup> is currently set by over 1400 clinical single gene sequencing tests <sup id="cite_ref-33" class="reference"><font size="2"><font color="#0066cc"><span>[</span>34<span>]</span></font></font></sup> (for example, errors in <font color="#0066cc">BRCA1</font> gene for <font color="#0066cc">breast cancer</font> risk analysis). As of June 2009, the <font color="#0066cc">Archon X Prize</font> for Genomics remains unclaimed.</p>
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<h2><span class="mw-headline"><font color="#000000">Race to commercialization</font></span></h2>
<p>In 2007, <font color="#0066cc">Applied Biosystems</font> started selling a new type of sequencer called SOLiD System, with the first sale to <font color="#0066cc">Helicos Biosciences</font> in 2008.<sup id="cite_ref-34" class="reference"><font size="2"><font color="#0066cc"><span>[</span>35<span>]</span></font></font></sup> Helicos stated that, utilizing the new sequencers, they will attempt to provide a full genome sequencing service with a target price of $72,000 per sample.<sup id="cite_ref-pagewanted1_35-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>36<span>]</span></font></font></sup> However, this price point is still too high some applications, and is only competitive to DNA arrays (at $500 per sample) in cases where more than 0.1% of the genome is desired.</p>
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<p><font color="#000000">In October 2006, the X Prize Foundation, working in collaboration with the J. Craig Venter Science Foundation, established the Archon X Prize for Genomics,<sup id="cite_ref-30" class="reference"><font size="2"><span>[</span>31<span>]</span></font></sup> intending to award US$10&nbsp;million to &quot;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 $10,000&nbsp;per genome.&quot;<sup id="cite_ref-31" class="reference"><font size="2"><span>[</span>32<span>]</span></font></sup> However, higher accuracy rates (or confirmatory methods) are desirable for some clinical applications. An error rate of 1&nbsp;in 100,000&nbsp;bases, out of a total of six billion bases in the human diploid genome, would mean about 60,000&nbsp;errors per genome, which is a significant number of false positives and negatives. For the latter it is not known where the errors occur . The error rates required for widespread clinical use, such as Predictive Medicine<sup id="cite_ref-pmid17055251_32-0" class="reference"><font size="2"><span>[</span>33<span>]</span></font></sup> is currently set by over 1400 clinical single gene sequencing tests <sup id="cite_ref-33" class="reference"><font size="2"><span>[</span>34<span>]</span></font></sup> (for example, errors in BRCA1 gene for breast cancer risk analysis). As of June 2009, the Archon X Prize for Genomics remains unclaimed.</font></p>
<p>In 2008 and 2009, both public and private companies have emerged that are now in a competitive race to be the <font color="#0066cc">first mover</font> to provide a full genome sequencing platform that is commercially robust for both research and clinical use,<sup id="cite_ref-36" class="reference"><font size="2"><font color="#0066cc"><span>[</span>37<span>]</span></font></font></sup> including <font color="#0066cc">Illumina</font>,<sup id="cite_ref-37" class="reference"><font size="2"><font color="#0066cc"><span>[</span>38<span>]</span></font></font></sup> <font color="#0066cc">Sequenom</font>,<sup id="cite_ref-38" class="reference"><font size="2"><font color="#0066cc"><span>[</span>39<span>]</span></font></font></sup> <font color="#0066cc">454 Life Sciences</font>,<sup id="cite_ref-genengnews1_39-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>40<span>]</span></font></font></sup> <font color="#0066cc">Pacific Biosciences</font>,<sup id="cite_ref-40" class="reference"><font size="2"><font color="#0066cc"><span>[</span>41<span>]</span></font></font></sup> <font color="#0066cc">Complete Genomics</font>,<sup id="cite_ref-41" class="reference"><font size="2"><font color="#0066cc"><span>[</span>42<span>]</span></font></font></sup> <font color="#0066cc">Intelligent Bio-Systems</font>,<sup id="cite_ref-42" class="reference"><font size="2"><font color="#0066cc"><span>[</span>43<span>]</span></font></font></sup> <font color="#0066cc">Genome Corp</font>.,<sup id="cite_ref-43" class="reference"><font size="2"><font color="#0066cc"><span>[</span>44<span>]</span></font></font></sup> and <font color="#0066cc">Helicos BioScience</font><sup id="cite_ref-44" class="reference"><font size="2"><font color="#0066cc"><span>[</span>45<span>]</span></font></font></sup>. These companies are heavily financed and backed by venture capitalists, hedge funds, investment banks and, in the case of Illumina, Sequenom and 454, heavy re-investment of revenue into research and development, mergers and acquisitions, and licensing initiatives.<sup id="cite_ref-45" class="reference"><font size="2"><font color="#0066cc"><span>[</span>46<span>]</span></font></font></sup><sup id="cite_ref-46" class="reference"><font size="2"><font color="#0066cc"><span>[</span>47<span>]</span></font></font></sup><sup id="cite_ref-47" class="reference"><font size="2"><font color="#0066cc"><span>[</span>48<span>]</span></font></font></sup></p>
+
<p><font color="#000000">In 2007, Applied Biosystems started selling a new type of sequencer called SOLiD System, with the first sale to Helicos Biosciences in 2008.<sup id="cite_ref-34" class="reference"><font size="2"><span>[</span>35<span>]</span></font></sup> Helicos stated that, utilizing the new sequencers, they will attempt to provide a full genome sequencing service with a target price of $72,000 per sample.<sup id="cite_ref-pagewanted1_35-0" class="reference"><font size="2"><span>[</span>36<span>]</span></font></sup> However, this price point is still too high some applications, and is only competitive to DNA arrays (at $500 per sample) in cases where more than 0.1% of the genome is desired.</font></p>
<p>In the race to commercialize full genome sequencing, companies have made claims about being able to offer a service at a specific time for a specific price that have turned out to not be true. Intelligent Bio-Systems stated in November 2007 that by the end of 2008 they would release a platform capable of a providing a $5,000 full genome sequence, but, as of March 2009, no such platform has yet to be released.<sup id="cite_ref-48" class="reference"><font size="2"><font color="#0066cc"><span>[</span>49<span>]</span></font></font></sup></p>
+
<p><font color="#000000">In 2008 and 2009, both public and private companies have emerged that are now in a competitive race to be the first mover to provide a full genome sequencing platform that is commercially robust for both research and clinical use,<sup id="cite_ref-36" class="reference"><font size="2"><span>[</span>37<span>]</span></font></sup> including Illumina,<sup id="cite_ref-37" class="reference"><font size="2"><span>[</span>38<span>]</span></font></sup> Sequenom,<sup id="cite_ref-38" class="reference"><font size="2"><span>[</span>39<span>]</span></font></sup> 454 Life Sciences,<sup id="cite_ref-genengnews1_39-0" class="reference"><font size="2"><span>[</span>40<span>]</span></font></sup> Pacific Biosciences,<sup id="cite_ref-40" class="reference"><font size="2"><span>[</span>41<span>]</span></font></sup> Complete Genomics,<sup id="cite_ref-41" class="reference"><font size="2"><span>[</span>42<span>]</span></font></sup> Intelligent Bio-Systems,<sup id="cite_ref-42" class="reference"><font size="2"><span>[</span>43<span>]</span></font></sup> Genome Corp.,<sup id="cite_ref-43" class="reference"><font size="2"><span>[</span>44<span>]</span></font></sup> and Helicos BioScience<sup id="cite_ref-44" class="reference"><font size="2"><span>[</span>45<span>]</span></font></sup>. These companies are heavily financed and backed by venture capitalists, hedge funds, investment banks and, in the case of Illumina, Sequenom and 454, heavy re-investment of revenue into research and development, mergers and acquisitions, and licensing initiatives.<sup id="cite_ref-45" class="reference"><font size="2"><span>[</span>46<span>]</span></font></sup><sup id="cite_ref-46" class="reference"><font size="2"><span>[</span>47<span>]</span></font></sup><sup id="cite_ref-47" class="reference"><font size="2"><span>[</span>48<span>]</span></font></sup></font></p>
<p>Pacific Biosciences stated that they will start selling their full genome sequencers in early 2010. While they didn't disclose the cost to sequence a single genome, they did state they may not release their second-generation machine capable of a $1,000 genome until 2013.<sup id="cite_ref-pagewanted1_35-1" class="reference"><font size="2"><font color="#0066cc"><span>[</span>36<span>]</span></font></font></sup> Complete Genomics, however, stated that they'll be able to provide a $5,000&nbsp;full genome sequencing service by the summer of 2009.<sup id="cite_ref-49" class="reference"><font size="2"><font color="#0066cc"><span>[</span>50<span>]</span></font></font></sup> The <font color="#0066cc">accuracy</font>, <font color="#0066cc">precision</font>, and <font color="#0066cc">reproducibility</font> of both Pacific Biosciences and Complete Genomics technology, however, is still unknown.</p>
+
<p><font color="#000000">In the race to commercialize full genome sequencing, companies have made claims about being able to offer a service at a specific time for a specific price that have turned out to not be true. Intelligent Bio-Systems stated in November 2007 that by the end of 2008 they would release a platform capable of a providing a $5,000 full genome sequence, but, as of March 2009, no such platform has yet to be released.<sup id="cite_ref-48" class="reference"><font size="2"><span>[</span>49<span>]</span></font></sup></font></p>
<p>A <font color="#0066cc">personal genomics</font> company located in Massachusetts, Knome.com, currently provides genome sequencing services but the cost is about $99,500 per genome (down from $350,000 per genome initially),<sup id="cite_ref-50" class="reference"><font size="2"><font color="#0066cc"><span>[</span>51<span>]</span></font></font></sup> the turn-around time is unknown, the accuracy is unknown, and the number of people was limited to 20 for the first year, and is still considered early stage <font color="#0066cc">commercialization</font> of full genome sequencing, focusing on wealthy customers.<sup id="cite_ref-51" class="reference"><font size="2"><font color="#0066cc"><span>[</span>52<span>]</span></font></font></sup></p>
+
<p><font color="#000000">Pacific Biosciences stated that they will start selling their full genome sequencers in early 2010. While they didn't disclose the cost to sequence a single genome, they did state they may not release their second-generation machine capable of a $1,000 genome until 2013.<sup id="cite_ref-pagewanted1_35-1" class="reference"><font size="2"><span>[</span>36<span>]</span></font></sup> Complete Genomics, however, stated that they'll be able to provide a $5,000&nbsp;full genome sequencing service by the summer of 2009.<sup id="cite_ref-49" class="reference"><font size="2"><span>[</span>50<span>]</span></font></sup> The accuracy, precision, and reproducibility of both Pacific Biosciences and Complete Genomics technology, however, is still unknown.</font></p>
<p>As of January 2009, there are no indications that any of these companies have been hindered by the global recession. And thus, the race appears to be proceeding forward at full speed. <sup id="cite_ref-52" class="reference"><font size="2"><font color="#0066cc"><span>[</span>53<span>]</span></font></font></sup></p>
+
<p><font color="#000000">A personal genomics company located in Massachusetts, Knome.com, currently provides genome sequencing services but the cost is about $99,500 per genome (down from $350,000 per genome initially),<sup id="cite_ref-50" class="reference"><font size="2"><span>[</span>51<span>]</span></font></sup> the turn-around time is unknown, the accuracy is unknown, and the number of people was limited to 20 for the first year, and is still considered early stage commercialization of full genome sequencing, focusing on wealthy customers.<sup id="cite_ref-51" class="reference"><font size="2"><span>[</span>52<span>]</span></font></sup></font></p>
<p>At the end of 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 99.99%, meaning that there is an error in one out of every ten thousand base pairs. This means that their full sequence of the human genome will contain approximately 80,000-100,000 <font color="#0066cc">false positive</font> errors in each genome. However, this accuracy rate was based on Complete Genomics' sequence that was completed utilizing a 90x depth of coverage (each base in the genome was sequenced 90 times) while their commercialized sequence is reported to be only 40x, so the accuracy may be substantially lower unless they can find some way to improve it before their first service release planned for the summer 2009. This accuracy rate may be acceptable for research purposes, and clinical use would require confirmation by other methods of any reportable alleles.<sup id="cite_ref-53" class="reference"><font size="2"><font color="#0066cc"><span>[</span>54<span>]</span></font></font></sup><sup id="cite_ref-54" class="reference"><font size="2"><font color="#0066cc"><span>[</span>55<span>]</span></font></font></sup> In March 2009, it was announced that Complete Genomics has signed a deal with the <font color="#0066cc">Broad Institute</font> to sequence cancer patient's genomes and will be sequencing five full genomes to start.<sup id="cite_ref-55" class="reference"><font size="2"><font color="#0066cc"><span>[</span>56<span>]</span></font></font></sup> In April 2009, Complete Genomics announced that it plans to sequence 1,000 full genome's between June 2009 and the end of the year and that they plan to be able to sequence one million full genomes <em>per year</em> by 2013.<sup id="cite_ref-56" class="reference"><font size="2"><font color="#0066cc"><span>[</span>57<span>]</span></font></font></sup> Complete Genomics plans to officially launch in June 2009, although it is unknown if their lab will have received <font color="#0066cc">CLIA</font>-certification by that time.</p>
+
<p><font color="#000000">As of January 2009, there are no indications that any of these companies have been hindered by the global recession. And thus, the race appears to be proceeding forward at full speed. <sup id="cite_ref-52" class="reference"><font size="2"><span>[</span>53<span>]</span></font></sup></font></p>
<p>In June 2009, <font color="#0066cc">Illumina</font> announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30X for $48,000 per genome.<sup id="cite_ref-57" class="reference"><font size="2"><font color="#0066cc"><span>[</span>58<span>]</span></font></font></sup> 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.<sup id="cite_ref-58" class="reference"><font size="2"><font color="#0066cc"><span>[</span>59<span>]</span></font></font></sup><sup id="cite_ref-59" class="reference"><font size="2"><font color="#0066cc"><span>[</span>60<span>]</span></font></font></sup> Jay Flatley, Illumina's President &amp; CEO, stated that &quot;during the next five years, perhaps markedly sooner,&quot; the price point for full genome sequencing will fall from $48,000 to under $1,000.<sup id="cite_ref-60" class="reference"><font size="2"><font color="#0066cc"><span>[</span>61<span>]</span></font></font></sup> Illumina has already signed agreements to supply full genome sequencing services to multiple direct-to-consumer personal genomics companies.</p>
+
<p><font color="#000000">At the end of February </font><font color="#000000">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 99.99%, meaning that there is an error in one out of every ten thousand base pairs. 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 90x depth of coverage (each base in the genome was sequenced 90 times) while their commercialized sequence is reported to be only 40x, so the accuracy may be substantially lower unless they can find some way to improve it before their first service release planned for the summer 2009. This accuracy rate may be acceptable for research purposes, and clinical use would require confirmation by other methods of any reportable alleles.<sup id="cite_ref-53" class="reference"><font size="2"><span>[</span>54<span>]</span></font></sup><sup id="cite_ref-54" class="reference"><font size="2"><span>[</span>55<span>]</span></font></sup> In March 2009, it was announced that Complete Genomics has signed a deal with the Broad Institute to sequence cancer patient's genomes and will be sequencing five full genomes to start.<sup id="cite_ref-55" class="reference"><font size="2"><span>[</span>56<span>]</span></font></sup> In April 2009, Complete Genomics announced that it plans to sequence 1,000 full genome's between June 2009 and the end of the year and that they plan to be able to sequence one million full genomes <em>per year</em> by 2013.<sup id="cite_ref-56" class="reference"><font size="2"><span>[</span>57<span>]</span></font></sup> Complete Genomics plans to officially launch in June 2009, although it is unknown if their lab will have received CLIA-certification by that time.</font></p>
 +
<p><font color="#000000">In June 2009, Illumina announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30X for $48,000 per genome.<sup id="cite_ref-57" class="reference"><font size="2"><span>[</span>58<span>]</span></font></sup> This is still expensive for </font><font color="#000000">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.<sup id="cite_ref-58" class="reference"><font size="2"><span>[</span>59<span>]</span></font></sup><sup id="cite_ref-59" class="reference"><font size="2"><span>[</span>60<span>]</span></font></sup> Jay Flatley, Illumina's President &amp; CEO, stated that &quot;during the next five years, perhaps markedly sooner,&quot; the price point for full genome sequencing will fall from $48,000 to under $1,000.<sup id="cite_ref-60" class="reference"><font size="2"><span>[</span>61<span>]</span></font></sup> Illumina has already signed agreements to supply full genome sequencing services to multiple direct-to-consumer personal genomics companies.</font></p>
 +
<p><font color="#000000">&nbsp;</font></p>
 +
<h2><span class="mw-headline"><font color="#000000">Disruptive technology</font></span></h2>
 +
<p><font color="#000000">Full genome sequencing provides information on a genome that is orders of magnitude larger than that provided by the current leader in sequencing technology, DNA arrays. For humans, DNA arrays currently provides genotypic information on up to one million genetic variants,<sup id="cite_ref-61" class="reference"><font size="2"><span>[</span>62<span>]</span></font></sup><sup id="cite_ref-pmid18803882_62-0" class="reference"><font size="2"><span>[</span>63<span>]</span></font></sup><sup id="cite_ref-63" class="reference"><font size="2"><span>[</span>64<span>]</span></font></sup> while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000&nbsp;times more data. Because of this, full genome sequencing is considered disruptive to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500&nbsp;per 1 million basepairs).<sup id="cite_ref-genengnews1_39-1" class="reference"><font size="2"><span>[</span>40<span>]</span></font></sup> Agilent, another established DNA array manufacturer, is working on targeted (selective region) genome sequencing technologies<sup id="cite_ref-64" class="reference"><font size="2"><span>[</span>65<span>]</span></font></sup>. It is thought that Affymetrix, 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.<sup id="cite_ref-65" class="reference"><font size="2"><span>[</span>66<span>]</span></font></sup><sup id="cite_ref-66" class="reference"><font size="2"><span>[</span>67<span>]</span></font></sup><sup id="cite_ref-pmid17108930_67-0" class="reference"><font size="2"><span>[</span>68<span>]</span></font></sup> 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. 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.<sup id="cite_ref-pmid18846083_68-0" class="reference"><font size="2"><span>[</span>69<span>]</span></font></sup></font></p>
 +
<p>&nbsp;</p>
 +
<h2><span class="mw-headline"><font color="#000000">Societal impact</font></span></h2>
 +
<div class="rellink"><font color="#000000">Further information: Personal genomics - predictive medicine services already available</font></div>
 +
<p><font color="#000000">Inexpensive, time-efficient full genome sequencing will be a major accomplishment not only for the field of Genomics, but for the entire human civilization 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. 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 and Personalized Medicine 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. However, it should be recognized that despite advancements in genome sequencing technology, incomplete understanding of the significance of individual variants or combinations of variants will limit the widespread usefulness of full genome sequencing in medicine until its clinical utility can be demonstrated.</font></p>
 +
<p><font color="#000000">Illumina's CEO, Jay Flatley, stated in February 2009 that &quot;A complete DNA read-out for every newborn will be technically feasible and affordable in less than five years, promising a revolution in healthcare&quot; and that &quot;by 2019 it will have become routine to map infants' genes when they are born.&quot;<sup id="cite_ref-69" class="reference"><font size="2"><span>[</span>70<span>]</span></font></sup> However, this potential use of genome sequencing runs counter to established norms for genetic testing of asymptomatic minors that have been well established in the field of genetic counseling.<sup id="cite_ref-70" class="reference"><font size="2"><span>[</span>71<span>]</span></font></sup><sup id="cite_ref-71" class="reference"><font size="2"><span>[</span>72<span>]</span></font></sup><sup id="cite_ref-72" class="reference"><font size="2"><span>[</span>73<span>]</span></font></sup><sup id="cite_ref-73" class="reference"><font size="2"><span>[</span>74<span>]</span></font></sup></font></p>
 
<p>&nbsp;</p>
 
<p>&nbsp;</p>
<h2><span class="mw-headline">Disruptive technology</span></h2>
+
<h2><span class="mw-headline"><font color="#000000">See also</font></span></h2>
<p>Full genome sequencing provides information on a genome that is orders of magnitude larger than that provided by the current leader in sequencing technology, DNA arrays. For humans, DNA arrays currently provides genotypic information on up to one million genetic variants,<sup id="cite_ref-61" class="reference"><font size="2"><font color="#0066cc"><span>[</span>62<span>]</span></font></font></sup><sup id="cite_ref-pmid18803882_62-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>63<span>]</span></font></font></sup><sup id="cite_ref-63" class="reference"><font size="2"><font color="#0066cc"><span>[</span>64<span>]</span></font></font></sup> while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000&nbsp;times more data. Because of this, full genome sequencing is considered <font color="#0066cc">disruptive</font> to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500&nbsp;per 1 million basepairs).<sup id="cite_ref-genengnews1_39-1" class="reference"><font size="2"><font color="#0066cc"><span>[</span>40<span>]</span></font></font></sup> <font color="#0066cc">Agilent</font>, another established DNA array manufacturer, is working on targeted (selective region) genome sequencing technologies<sup id="cite_ref-64" class="reference"><font size="2"><font color="#0066cc"><span>[</span>65<span>]</span></font></font></sup>. It is thought that <font color="#0066cc">Affymetrix</font>, 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.<sup id="cite_ref-65" class="reference"><font size="2"><font color="#0066cc"><span>[</span>66<span>]</span></font></font></sup><sup id="cite_ref-66" class="reference"><font size="2"><font color="#0066cc"><span>[</span>67<span>]</span></font></font></sup><sup id="cite_ref-pmid17108930_67-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>68<span>]</span></font></font></sup> 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 <font color="#0066cc">economies of scale</font>. 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.<sup id="cite_ref-pmid18846083_68-0" class="reference"><font size="2"><font color="#0066cc"><span>[</span>69<span>]</span></font></font></sup></p>
 
<p><font color="#0066cc" size="2"></font></p>
 
<h2><span class="mw-headline">Societal impact</span></h2>
 
<div class="rellink">Further information: <font color="#0066cc">Personal genomics - predictive medicine services already available</font></div>
 
<p>Inexpensive, time-efficient full genome sequencing will be a major accomplishment not only for the field of <font color="#0066cc">Genomics</font>, but for the entire human <font color="#0066cc">civilization</font> 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 <font color="#0066cc">genetic counselors</font>, 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, <font color="#0066cc">preventive medicine</font>. Full genome sequencing will allow <font color="#0066cc">health care professionals</font> 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 <font color="#0066cc">Predictive Medicine</font> and <font color="#0066cc">Personalized Medicine</font> 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. However, it should be recognized that despite advancements in genome sequencing technology, incomplete understanding of the significance of individual variants or combinations of variants will limit the widespread usefulness of full genome sequencing in medicine until its clinical utility can be demonstrated.</p>
 
<p>Illumina's CEO, Jay Flatley, stated in February 2009 that &quot;A complete DNA read-out for every newborn will be technically feasible and affordable in less than five years, promising a revolution in healthcare&quot; and that &quot;by 2019 it will have become routine to map infants' genes when they are born.&quot;<sup id="cite_ref-69" class="reference"><font size="2"><font color="#0066cc"><span>[</span>70<span>]</span></font></font></sup> However, this potential use of genome sequencing runs counter to established norms for <font color="#0066cc">genetic testing</font> of asymptomatic minors that have been well established in the field of <font color="#0066cc">genetic counseling</font>.<sup id="cite_ref-70" class="reference"><font size="2"><font color="#0066cc"><span>[</span>71<span>]</span></font></font></sup><sup id="cite_ref-71" class="reference"><font size="2"><font color="#0066cc"><span>[</span>72<span>]</span></font></font></sup><sup id="cite_ref-72" class="reference"><font size="2"><font color="#0066cc"><span>[</span>73<span>]</span></font></font></sup><sup id="cite_ref-73" class="reference"><font size="2"><font color="#0066cc"><span>[</span>74<span>]</span></font></font></sup></p>
 
<p><font color="#0066cc" size="2"></font></p>
 
<h2><span class="mw-headline">See also</span></h2>
 
 
<ul>
 
<ul>
     <li><font color="#0066cc">DNA microarray</font></li>
+
     <li><font color="#000000">DNA microarray </font></li>
     <li><font color="#0066cc">DNA profiling</font></li>
+
     <li><font color="#000000">DNA profiling </font></li>
     <li><font color="#0066cc">Medical genetics</font></li>
+
     <li><font color="#000000">Medical genetics </font></li>
     <li><font color="#0066cc">Human Genome Project</font></li>
+
     <li><font color="#000000">Human Genome Project </font></li>
     <li><font color="#0066cc">Personal Genome Project</font></li>
+
     <li><font color="#000000">Personal Genome Project </font></li>
     <li><font color="#0066cc">List of sequenced eukaryotic genomes</font></li>
+
     <li><font color="#000000">List of sequenced eukaryotic genomes </font></li>
     <li><font color="#0066cc">List of sequenced bacterial genomes</font></li>
+
     <li><font color="#000000">List of sequenced bacterial genomes </font></li>
     <li><font color="#0066cc">List of sequenced archaeal genomes</font></li>
+
     <li><font color="#000000">List of sequenced archaeal genomes </font></li>
 
</ul>
 
</ul>
<p><a id="References" name="References"><font color="#0066cc"></font></a></p>
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<p><font color="#000000"><a id="References" name="References"></a></font></p>
<h2><span class="mw-headline">References</span></h2>
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<h2><span class="mw-headline"><font color="#000000">References</font></span></h2>
 
<div style="-moz-column-width: 30em; column-width: 30em" class="references-small references-column-width">
 
<div style="-moz-column-width: 30em; column-width: 30em" class="references-small references-column-width">
 
<ol class="references">
 
<ol class="references">
 
     <li id="cite_note-0"><strong><a href="#cite_ref-0"><font color="#0066cc">^</font></a></strong> Kijk magazine, 01 January 2009</li>
 
     <li id="cite_note-0"><strong><a href="#cite_ref-0"><font color="#0066cc">^</font></a></strong> Kijk magazine, 01 January 2009</li>
     <li id="cite_note-pmid17554300-1"><strong><a href="#cite_ref-pmid17554300_1-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal">&quot;Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls&quot;. <em>Nature</em> <strong>447</strong> (7145): 661&ndash;78. June 2007. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1038%2Fnature05911" href="http://dx.doi.org/10.1038%2Fnature05911" rel="nofollow"><font color="#0066cc">10.1038/nature05911</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17554300" href="http://www.ncbi.nlm.nih.gov/pubmed/17554300"><font color="#0066cc">PMID 17554300</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Genome-wide+association+study+of+14%2C000+cases+of+seven+common+diseases+and+3%2C000+shared+controls&amp;rft.jtitle=Nature&amp;rft.date=June+2007&amp;rft.volume=447&amp;rft.issue=7145&amp;rft.pages=661%E2%80%9378&amp;rft_id=info:doi/10.1038%2Fnature05911&amp;rft_id=info:pmid/17554300&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
+
     <li id="cite_note-pmid17554300-1"><strong><a href="#cite_ref-pmid17554300_1-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal">&quot;Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls&quot;. <em>Nature</em> <strong>447</strong> (7145): 661&ndash;78. June 2007. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1038%2Fnature05911" rel="nofollow" href="http://dx.doi.org/10.1038%2Fnature05911"><font color="#0066cc">10.1038/nature05911</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17554300" href="http://www.ncbi.nlm.nih.gov/pubmed/17554300"><font color="#0066cc">PMID 17554300</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Genome-wide+association+study+of+14%2C000+cases+of+seven+common+diseases+and+3%2C000+shared+controls&amp;rft.jtitle=Nature&amp;rft.date=June+2007&amp;rft.volume=447&amp;rft.issue=7145&amp;rft.pages=661%E2%80%9378&amp;rft_id=info:doi/10.1038%2Fnature05911&amp;rft_id=info:pmid/17554300&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-pmid17898773-2"><strong><a href="#cite_ref-pmid17898773_2-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFMailman_MD.2C_Feolo_M.2C_Jin_Y.2C_Kimura_M.2C_Tryka_K.2C_Bagoutdinov_R.2C_Hao_L.2C_Kiang_A.2C_Paschall_J.2C_Phan_L.2C_Popova_N.2C_Pretel_S.2C_Ziyabari_L.2C_Lee_M.2C_Shao_Y.2C_Wang_ZY.2C_Sirotkin_K.2C_Ward_M.2C_Kholodov_M.2C_Zbicz_K.2C_Beck_J.2C_Kimelman_M.2C_Shevelev_S.2C_Preuss_D.2C_Yaschenko_E.2C_Graeff_A.2C_Ostell_J.2C_Sherry_ST2007">Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, Bagoutdinov R, Hao L, Kiang A, Paschall J, Phan L, Popova N, Pretel S, Ziyabari L, Lee M, Shao Y, Wang ZY, Sirotkin K, Ward M, Kholodov M, Zbicz K, Beck J, Kimelman M, Shevelev S, Preuss D, Yaschenko E, Graeff A, Ostell J, Sherry ST (October 2007). &quot;<a class="external text" title="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=2031016" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=2031016" rel="nofollow"><font color="#0066cc">The NCBI dbGaP database of genotypes and phenotypes</font></a>&quot;. <em>Nat. Genet.</em> <strong>39</strong> (10): 1181&ndash;6. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1038%2Fng1007-1181" href="http://dx.doi.org/10.1038%2Fng1007-1181" rel="nofollow"><font color="#0066cc">10.1038/ng1007-1181</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17898773" href="http://www.ncbi.nlm.nih.gov/pubmed/17898773"><font color="#0066cc">PMID 17898773</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+NCBI+dbGaP+database+of+genotypes+and+phenotypes&amp;rft.jtitle=Nat.+Genet.&amp;rft.aulast=Mailman+MD%2C+Feolo+M%2C+Jin+Y%2C+Kimura+M%2C+Tryka+K%2C+Bagoutdinov+R%2C+Hao+L%2C+Kiang+A%2C+Paschall+J%2C+Phan+L%2C+Popova+N%2C+Pretel+S%2C+Ziyabari+L%2C+Lee+M%2C+Shao+Y%2C+Wang+ZY%2C+Sirotkin+K%2C+Ward+M%2C+Kholodov+M%2C+Zbicz+K%2C+Beck+J%2C+Kimelman+M%2C+Shevelev+S%2C+Preuss+D%2C+Yaschenko+E%2C+Graeff+A%2C+Ostell+J%2C+Sherry+ST&amp;rft.au=Mailman+MD%2C+Feolo+M%2C+Jin+Y%2C+Kimura+M%2C+Tryka+K%2C+Bagoutdinov+R%2C+Hao+L%2C+Kiang+A%2C+Paschall+J%2C+Phan+L%2C+Popova+N%2C+Pretel+S%2C+Ziyabari+L%2C+Lee+M%2C+Shao+Y%2C+Wang+ZY%2C+Sirotkin+K%2C+Ward+M%2C+Kholodov+M%2C+Zbicz+K%2C+Beck+J%2C+Kimelman+M%2C+Shevelev+S%2C+Preuss+D%2C+Yaschenko+E%2C+Graeff+A%2C+Ostell+J%2C+Sherry+ST&amp;rft.date=October+2007&amp;rft.volume=39&amp;rft.issue=10&amp;rft.pages=1181%E2%80%936&amp;rft_id=info:doi/10.1038%2Fng1007-1181&amp;rft_id=info:pmid/17898773&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-pmid17898773-2"><strong><a href="#cite_ref-pmid17898773_2-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFMailman_MD.2C_Feolo_M.2C_Jin_Y.2C_Kimura_M.2C_Tryka_K.2C_Bagoutdinov_R.2C_Hao_L.2C_Kiang_A.2C_Paschall_J.2C_Phan_L.2C_Popova_N.2C_Pretel_S.2C_Ziyabari_L.2C_Lee_M.2C_Shao_Y.2C_Wang_ZY.2C_Sirotkin_K.2C_Ward_M.2C_Kholodov_M.2C_Zbicz_K.2C_Beck_J.2C_Kimelman_M.2C_Shevelev_S.2C_Preuss_D.2C_Yaschenko_E.2C_Graeff_A.2C_Ostell_J.2C_Sherry_ST2007">Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, Bagoutdinov R, Hao L, Kiang A, Paschall J, Phan L, Popova N, Pretel S, Ziyabari L, Lee M, Shao Y, Wang ZY, Sirotkin K, Ward M, Kholodov M, Zbicz K, Beck J, Kimelman M, Shevelev S, Preuss D, Yaschenko E, Graeff A, Ostell J, Sherry ST (October 2007). &quot;<a class="external text" title="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=2031016" rel="nofollow" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=2031016"><font color="#0066cc">The NCBI dbGaP database of genotypes and phenotypes</font></a>&quot;. <em>Nat. Genet.</em> <strong>39</strong> (10): 1181&ndash;6. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1038%2Fng1007-1181" rel="nofollow" href="http://dx.doi.org/10.1038%2Fng1007-1181"><font color="#0066cc">10.1038/ng1007-1181</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17898773" href="http://www.ncbi.nlm.nih.gov/pubmed/17898773"><font color="#0066cc">PMID 17898773</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+NCBI+dbGaP+database+of+genotypes+and+phenotypes&amp;rft.jtitle=Nat.+Genet.&amp;rft.aulast=Mailman+MD%2C+Feolo+M%2C+Jin+Y%2C+Kimura+M%2C+Tryka+K%2C+Bagoutdinov+R%2C+Hao+L%2C+Kiang+A%2C+Paschall+J%2C+Phan+L%2C+Popova+N%2C+Pretel+S%2C+Ziyabari+L%2C+Lee+M%2C+Shao+Y%2C+Wang+ZY%2C+Sirotkin+K%2C+Ward+M%2C+Kholodov+M%2C+Zbicz+K%2C+Beck+J%2C+Kimelman+M%2C+Shevelev+S%2C+Preuss+D%2C+Yaschenko+E%2C+Graeff+A%2C+Ostell+J%2C+Sherry+ST&amp;rft.au=Mailman+MD%2C+Feolo+M%2C+Jin+Y%2C+Kimura+M%2C+Tryka+K%2C+Bagoutdinov+R%2C+Hao+L%2C+Kiang+A%2C+Paschall+J%2C+Phan+L%2C+Popova+N%2C+Pretel+S%2C+Ziyabari+L%2C+Lee+M%2C+Shao+Y%2C+Wang+ZY%2C+Sirotkin+K%2C+Ward+M%2C+Kholodov+M%2C+Zbicz+K%2C+Beck+J%2C+Kimelman+M%2C+Shevelev+S%2C+Preuss+D%2C+Yaschenko+E%2C+Graeff+A%2C+Ostell+J%2C+Sherry+ST&amp;rft.date=October+2007&amp;rft.volume=39&amp;rft.issue=10&amp;rft.pages=1181%E2%80%936&amp;rft_id=info:doi/10.1038%2Fng1007-1181&amp;rft_id=info:pmid/17898773&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-3"><strong><a href="#cite_ref-3"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWade2007" class="news">Wade, Nicholas (September 4, 2007). &quot;<a class="external text" title="http://www.nytimes.com/2007/09/04/science/04vent.html" href="http://www.nytimes.com/2007/09/04/science/04vent.html" rel="nofollow"><font color="#0066cc">In the Genome Race, the Sequel Is Personal</font></a>&quot;. New York Times<span class="printonly">. <a class="external free" title="http://www.nytimes.com/2007/09/04/science/04vent.html" href="http://www.nytimes.com/2007/09/04/science/04vent.html" rel="nofollow"><font color="#0066cc">http://www.nytimes.com/2007/09/04/science/04vent.html</font></a></span><span class="reference-accessdate">. Retrieved on February 22, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=In+the+Genome+Race%2C+the+Sequel+Is+Personal&amp;rft.atitle=&amp;rft.aulast=Wade&amp;rft.aufirst=Nicholas&amp;rft.au=Wade%2C+Nicholas&amp;rft.date=September+4%2C+2007&amp;rft.pub=New+York+Times&amp;rft_id=http%3A%2F%2Fwww.nytimes.com%2F2007%2F09%2F04%2Fscience%2F04vent.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-3"><strong><a href="#cite_ref-3"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWade2007" class="news">Wade, Nicholas (September 4, 2007). &quot;<a class="external text" title="http://www.nytimes.com/2007/09/04/science/04vent.html" rel="nofollow" href="http://www.nytimes.com/2007/09/04/science/04vent.html"><font color="#0066cc">In the Genome Race, the Sequel Is Personal</font></a>&quot;. New York Times<span class="printonly">. <a class="external free" title="http://www.nytimes.com/2007/09/04/science/04vent.html" rel="nofollow" href="http://www.nytimes.com/2007/09/04/science/04vent.html"><font color="#0066cc">http://www.nytimes.com/2007/09/04/science/04vent.html</font></a></span><span class="reference-accessdate">. Retrieved on February 22, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=In+the+Genome+Race%2C+the+Sequel+Is+Personal&amp;rft.atitle=&amp;rft.aulast=Wade&amp;rft.aufirst=Nicholas&amp;rft.au=Wade%2C+Nicholas&amp;rft.date=September+4%2C+2007&amp;rft.pub=New+York+Times&amp;rft_id=http%3A%2F%2Fwww.nytimes.com%2F2007%2F09%2F04%2Fscience%2F04vent.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-4"><strong><a href="#cite_ref-4"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFNature" class="web">Nature. &quot;<a class="external text" title="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html" href="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html" rel="nofollow"><font color="#0066cc">Access&nbsp;: All about Craig: the first 'full' genome sequence</font></a>&quot;. Nature<span class="printonly">. <a class="external free" title="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html" href="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html" rel="nofollow"><font color="#0066cc">http://www.nature.com/nature/journal/v449/n7158/full/449006a.html</font></a></span><span class="reference-accessdate">. Retrieved on 2009-02-24</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Access+%3A+All+about+Craig%3A+the+first+%27full%27+genome+sequence&amp;rft.atitle=&amp;rft.aulast=Nature&amp;rft.au=Nature&amp;rft.pub=Nature&amp;rft_id=http%3A%2F%2Fwww.nature.com%2Fnature%2Fjournal%2Fv449%2Fn7158%2Ffull%2F449006a.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-4"><strong><a href="#cite_ref-4"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFNature" class="web">Nature. &quot;<a class="external text" title="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html" rel="nofollow" href="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html"><font color="#0066cc">Access&nbsp;: All about Craig: the first 'full' genome sequence</font></a>&quot;. Nature<span class="printonly">. <a class="external free" title="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html" rel="nofollow" href="http://www.nature.com/nature/journal/v449/n7158/full/449006a.html"><font color="#0066cc">http://www.nature.com/nature/journal/v449/n7158/full/449006a.html</font></a></span><span class="reference-accessdate">. Retrieved on 2009-02-24</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Access+%3A+All+about+Craig%3A+the+first+%27full%27+genome+sequence&amp;rft.atitle=&amp;rft.aulast=Nature&amp;rft.au=Nature&amp;rft.pub=Nature&amp;rft_id=http%3A%2F%2Fwww.nature.com%2Fnature%2Fjournal%2Fv449%2Fn7158%2Ffull%2F449006a.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-pmid17803354-5"><strong><a href="#cite_ref-pmid17803354_5-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFLevy_S.2C_Sutton_G.2C_Ng_PC.2C_Feuk_L.2C_Halpern_AL.2C_Walenz_BP.2C_Axelrod_N.2C_Huang_J.2C_Kirkness_EF.2C_Denisov_G.2C_Lin_Y.2C_MacDonald_JR.2C_Pang_AW.2C_Shago_M.2C_Stockwell_TB.2C_Tsiamouri_A.2C_Bafna_V.2C_Bansal_V.2C_Kravitz_SA.2C_Busam_DA.2C_Beeson_KY.2C_McIntosh_TC.2C_Remington_KA.2C_Abril_JF.2C_Gill_J.2C_Borman_J.2C_Rogers_YH.2C_Frazier_ME.2C_Scherer_SW.2C_Strausberg_RL.2C_Venter_JC2007">Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G, Lin Y, MacDonald JR, Pang AW, Shago M, Stockwell TB, Tsiamouri A, Bafna V, Bansal V, Kravitz SA, Busam DA, Beeson KY, McIntosh TC, Remington KA, Abril JF, Gill J, Borman J, Rogers YH, Frazier ME, Scherer SW, Strausberg RL, Venter JC (September 2007). &quot;<a class="external text" title="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=1964779" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=1964779" rel="nofollow"><font color="#0066cc">The diploid genome sequence of an individual human</font></a>&quot;. <em>PLoS Biol.</em> <strong>5</strong> (10): e254. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1371%2Fjournal.pbio.0050254" href="http://dx.doi.org/10.1371%2Fjournal.pbio.0050254" rel="nofollow"><font color="#0066cc">10.1371/journal.pbio.0050254</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17803354" href="http://www.ncbi.nlm.nih.gov/pubmed/17803354"><font color="#0066cc">PMID 17803354</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+diploid+genome+sequence+of+an+individual+human&amp;rft.jtitle=PLoS+Biol.&amp;rft.aulast=Levy+S%2C+Sutton+G%2C+Ng+PC%2C+Feuk+L%2C+Halpern+AL%2C+Walenz+BP%2C+Axelrod+N%2C+Huang+J%2C+Kirkness+EF%2C+Denisov+G%2C+Lin+Y%2C+MacDonald+JR%2C+Pang+AW%2C+Shago+M%2C+Stockwell+TB%2C+Tsiamouri+A%2C+Bafna+V%2C+Bansal+V%2C+Kravitz+SA%2C+Busam+DA%2C+Beeson+KY%2C+McIntosh+TC%2C+Remington+KA%2C+Abril+JF%2C+Gill+J%2C+Borman+J%2C+Rogers+YH%2C+Frazier+ME%2C+Scherer+SW%2C+Strausberg+RL%2C+Venter+JC&amp;rft.au=Levy+S%2C+Sutton+G%2C+Ng+PC%2C+Feuk+L%2C+Halpern+AL%2C+Walenz+BP%2C+Axelrod+N%2C+Huang+J%2C+Kirkness+EF%2C+Denisov+G%2C+Lin+Y%2C+MacDonald+JR%2C+Pang+AW%2C+Shago+M%2C+Stockwell+TB%2C+Tsiamouri+A%2C+Bafna+V%2C+Bansal+V%2C+Kravitz+SA%2C+Busam+DA%2C+Beeson+KY%2C+McIntosh+TC%2C+Remington+KA%2C+Abril+JF%2C+Gill+J%2C+Borman+J%2C+Rogers+YH%2C+Frazier+ME%2C+Scherer+SW%2C+Strausberg+RL%2C+Venter+JC&amp;rft.date=September+2007&amp;rft.volume=5&amp;rft.issue=10&amp;rft.pages=e254&amp;rft_id=info:doi/10.1371%2Fjournal.pbio.0050254&amp;rft_id=info:pmid/17803354&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-pmid17803354-5"><strong><a href="#cite_ref-pmid17803354_5-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFLevy_S.2C_Sutton_G.2C_Ng_PC.2C_Feuk_L.2C_Halpern_AL.2C_Walenz_BP.2C_Axelrod_N.2C_Huang_J.2C_Kirkness_EF.2C_Denisov_G.2C_Lin_Y.2C_MacDonald_JR.2C_Pang_AW.2C_Shago_M.2C_Stockwell_TB.2C_Tsiamouri_A.2C_Bafna_V.2C_Bansal_V.2C_Kravitz_SA.2C_Busam_DA.2C_Beeson_KY.2C_McIntosh_TC.2C_Remington_KA.2C_Abril_JF.2C_Gill_J.2C_Borman_J.2C_Rogers_YH.2C_Frazier_ME.2C_Scherer_SW.2C_Strausberg_RL.2C_Venter_JC2007">Levy S, Sutton G, Ng PC, Feuk L, Halpern AL, Walenz BP, Axelrod N, Huang J, Kirkness EF, Denisov G, Lin Y, MacDonald JR, Pang AW, Shago M, Stockwell TB, Tsiamouri A, Bafna V, Bansal V, Kravitz SA, Busam DA, Beeson KY, McIntosh TC, Remington KA, Abril JF, Gill J, Borman J, Rogers YH, Frazier ME, Scherer SW, Strausberg RL, Venter JC (September 2007). &quot;<a class="external text" title="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=1964779" rel="nofollow" href="http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&amp;artid=1964779"><font color="#0066cc">The diploid genome sequence of an individual human</font></a>&quot;. <em>PLoS Biol.</em> <strong>5</strong> (10): e254. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1371%2Fjournal.pbio.0050254" rel="nofollow" href="http://dx.doi.org/10.1371%2Fjournal.pbio.0050254"><font color="#0066cc">10.1371/journal.pbio.0050254</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17803354" href="http://www.ncbi.nlm.nih.gov/pubmed/17803354"><font color="#0066cc">PMID 17803354</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+diploid+genome+sequence+of+an+individual+human&amp;rft.jtitle=PLoS+Biol.&amp;rft.aulast=Levy+S%2C+Sutton+G%2C+Ng+PC%2C+Feuk+L%2C+Halpern+AL%2C+Walenz+BP%2C+Axelrod+N%2C+Huang+J%2C+Kirkness+EF%2C+Denisov+G%2C+Lin+Y%2C+MacDonald+JR%2C+Pang+AW%2C+Shago+M%2C+Stockwell+TB%2C+Tsiamouri+A%2C+Bafna+V%2C+Bansal+V%2C+Kravitz+SA%2C+Busam+DA%2C+Beeson+KY%2C+McIntosh+TC%2C+Remington+KA%2C+Abril+JF%2C+Gill+J%2C+Borman+J%2C+Rogers+YH%2C+Frazier+ME%2C+Scherer+SW%2C+Strausberg+RL%2C+Venter+JC&amp;rft.au=Levy+S%2C+Sutton+G%2C+Ng+PC%2C+Feuk+L%2C+Halpern+AL%2C+Walenz+BP%2C+Axelrod+N%2C+Huang+J%2C+Kirkness+EF%2C+Denisov+G%2C+Lin+Y%2C+MacDonald+JR%2C+Pang+AW%2C+Shago+M%2C+Stockwell+TB%2C+Tsiamouri+A%2C+Bafna+V%2C+Bansal+V%2C+Kravitz+SA%2C+Busam+DA%2C+Beeson+KY%2C+McIntosh+TC%2C+Remington+KA%2C+Abril+JF%2C+Gill+J%2C+Borman+J%2C+Rogers+YH%2C+Frazier+ME%2C+Scherer+SW%2C+Strausberg+RL%2C+Venter+JC&amp;rft.date=September+2007&amp;rft.volume=5&amp;rft.issue=10&amp;rft.pages=e254&amp;rft_id=info:doi/10.1371%2Fjournal.pbio.0050254&amp;rft_id=info:pmid/17803354&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-6"><strong><a href="#cite_ref-6"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWade2007" class="web">Wade, Wade (June 1, 2007). &quot;<a class="external text" title="http://www.iht.com/articles/2007/06/01/america/dna.php" href="http://www.iht.com/articles/2007/06/01/america/dna.php" rel="nofollow"><font color="#0066cc">DNA pioneer Watson gets own genome map</font></a>&quot;. International Herald Tribune<span class="printonly">. <a class="external free" title="http://www.iht.com/articles/2007/06/01/america/dna.php" href="http://www.iht.com/articles/2007/06/01/america/dna.php" rel="nofollow"><font color="#0066cc">http://www.iht.com/articles/2007/06/01/america/dna.php</font></a></span><span class="reference-accessdate">. Retrieved on February 22, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=DNA+pioneer+Watson+gets+own+genome+map&amp;rft.atitle=&amp;rft.aulast=Wade&amp;rft.aufirst=Wade&amp;rft.au=Wade%2C+Wade&amp;rft.date=June+1%2C+2007&amp;rft.pub=International+Herald+Tribune&amp;rft_id=http%3A%2F%2Fwww.iht.com%2Farticles%2F2007%2F06%2F01%2Famerica%2Fdna.php&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-6"><strong><a href="#cite_ref-6"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWade2007" class="web">Wade, Wade (June 1, 2007). &quot;<a class="external text" title="http://www.iht.com/articles/2007/06/01/america/dna.php" rel="nofollow" href="http://www.iht.com/articles/2007/06/01/america/dna.php"><font color="#0066cc">DNA pioneer Watson gets own genome map</font></a>&quot;. International Herald Tribune<span class="printonly">. <a class="external free" title="http://www.iht.com/articles/2007/06/01/america/dna.php" rel="nofollow" href="http://www.iht.com/articles/2007/06/01/america/dna.php"><font color="#0066cc">http://www.iht.com/articles/2007/06/01/america/dna.php</font></a></span><span class="reference-accessdate">. Retrieved on February 22, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=DNA+pioneer+Watson+gets+own+genome+map&amp;rft.atitle=&amp;rft.aulast=Wade&amp;rft.aufirst=Wade&amp;rft.au=Wade%2C+Wade&amp;rft.date=June+1%2C+2007&amp;rft.pub=International+Herald+Tribune&amp;rft_id=http%3A%2F%2Fwww.iht.com%2Farticles%2F2007%2F06%2F01%2Famerica%2Fdna.php&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-7"><strong><a href="#cite_ref-7"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWade2007" class="news">Wade, Nicholas (May 31, 2007). &quot;<a class="external text" title="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html" href="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html" rel="nofollow"><font color="#0066cc">Genome of DNA Pioneer Is Deciphered</font></a>&quot;. New York Times<span class="printonly">. <a class="external free" title="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html" href="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html" rel="nofollow"><font color="#0066cc">http://www.nytimes.com/2007/05/31/science/31cnd-gene.html</font></a></span><span class="reference-accessdate">. Retrieved on February 21, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Genome+of+DNA+Pioneer+Is+Deciphered&amp;rft.atitle=&amp;rft.aulast=Wade&amp;rft.aufirst=Nicholas&amp;rft.au=Wade%2C+Nicholas&amp;rft.date=May+31%2C+2007&amp;rft.pub=New+York+Times&amp;rft_id=http%3A%2F%2Fwww.nytimes.com%2F2007%2F05%2F31%2Fscience%2F31cnd-gene.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-7"><strong><a href="#cite_ref-7"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWade2007" class="news">Wade, Nicholas (May 31, 2007). &quot;<a class="external text" title="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html" rel="nofollow" href="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html"><font color="#0066cc">Genome of DNA Pioneer Is Deciphered</font></a>&quot;. New York Times<span class="printonly">. <a class="external free" title="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html" rel="nofollow" href="http://www.nytimes.com/2007/05/31/science/31cnd-gene.html"><font color="#0066cc">http://www.nytimes.com/2007/05/31/science/31cnd-gene.html</font></a></span><span class="reference-accessdate">. Retrieved on February 21, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Genome+of+DNA+Pioneer+Is+Deciphered&amp;rft.atitle=&amp;rft.aulast=Wade&amp;rft.aufirst=Nicholas&amp;rft.au=Wade%2C+Nicholas&amp;rft.date=May+31%2C+2007&amp;rft.pub=New+York+Times&amp;rft_id=http%3A%2F%2Fwww.nytimes.com%2F2007%2F05%2F31%2Fscience%2F31cnd-gene.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-8"><strong><a href="#cite_ref-8"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWheeler_DA.2C_Srinivasan_M.2C_Egholm_M.2C_Shen_Y.2C_Chen_L.2C_McGuire_A.2C_He_W.2C_Chen_YJ.2C_Makhijani_V.2C_Roth_GT.2C_Gomes_X.2C_Tartaro_K.2C_Niazi_F.2C_Turcotte_CL.2C_Irzyk_GP.2C_Lupski_JR.2C_Chinault_C.2C_Song_XZ.2C_Liu_Y.2C_Yuan_Y.2C_Nazareth_L.2C_Qin_X.2C_Muzny_DM.2C_Margulies_M.2C_Weinstock_GM.2C_Gibbs_RA.2C_Rothberg_JM.2008">Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP, Lupski JR, Chinault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Qin X, Muzny DM, Margulies M, Weinstock GM, Gibbs RA, Rothberg JM. (2008). &quot;The complete genome of an individual by massively parallel DNA sequencing&quot;. <em>Nature</em> <strong>452</strong>: 872&ndash;6.. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/18421352" href="http://www.ncbi.nlm.nih.gov/pubmed/18421352"><font color="#0066cc">PMID 18421352</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+complete+genome+of+an+individual+by+massively+parallel+DNA+sequencing&amp;rft.jtitle=Nature&amp;rft.aulast=Wheeler+DA%2C+Srinivasan+M%2C+Egholm+M%2C+Shen+Y%2C+Chen+L%2C+McGuire+A%2C+He+W%2C+Chen+YJ%2C+Makhijani+V%2C+Roth+GT%2C+Gomes+X%2C+Tartaro+K%2C+Niazi+F%2C+Turcotte+CL%2C+Irzyk+GP%2C+Lupski+JR%2C+Chinault+C%2C+Song+XZ%2C+Liu+Y%2C+Yuan+Y%2C+Nazareth+L%2C+Qin+X%2C+Muzny+DM%2C+Margulies+M%2C+Weinstock+GM%2C+Gibbs+RA%2C+Rothberg+JM.&amp;rft.au=Wheeler+DA%2C+Srinivasan+M%2C+Egholm+M%2C+Shen+Y%2C+Chen+L%2C+McGuire+A%2C+He+W%2C+Chen+YJ%2C+Makhijani+V%2C+Roth+GT%2C+Gomes+X%2C+Tartaro+K%2C+Niazi+F%2C+Turcotte+CL%2C+Irzyk+GP%2C+Lupski+JR%2C+Chinault+C%2C+Song+XZ%2C+Liu+Y%2C+Yuan+Y%2C+Nazareth+L%2C+Qin+X%2C+Muzny+DM%2C+Margulies+M%2C+Weinstock+GM%2C+Gibbs+RA%2C+Rothberg+JM.&amp;rft.date=2008&amp;rft.volume=452&amp;rft.pages=872%E2%80%936.&amp;rft_id=info:pmid/18421352&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-8"><strong><a href="#cite_ref-8"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWheeler_DA.2C_Srinivasan_M.2C_Egholm_M.2C_Shen_Y.2C_Chen_L.2C_McGuire_A.2C_He_W.2C_Chen_YJ.2C_Makhijani_V.2C_Roth_GT.2C_Gomes_X.2C_Tartaro_K.2C_Niazi_F.2C_Turcotte_CL.2C_Irzyk_GP.2C_Lupski_JR.2C_Chinault_C.2C_Song_XZ.2C_Liu_Y.2C_Yuan_Y.2C_Nazareth_L.2C_Qin_X.2C_Muzny_DM.2C_Margulies_M.2C_Weinstock_GM.2C_Gibbs_RA.2C_Rothberg_JM.2008">Wheeler DA, Srinivasan M, Egholm M, Shen Y, Chen L, McGuire A, He W, Chen YJ, Makhijani V, Roth GT, Gomes X, Tartaro K, Niazi F, Turcotte CL, Irzyk GP, Lupski JR, Chinault C, Song XZ, Liu Y, Yuan Y, Nazareth L, Qin X, Muzny DM, Margulies M, Weinstock GM, Gibbs RA, Rothberg JM. (2008). &quot;The complete genome of an individual by massively parallel DNA sequencing&quot;. <em>Nature</em> <strong>452</strong>: 872&ndash;6.. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/18421352" href="http://www.ncbi.nlm.nih.gov/pubmed/18421352"><font color="#0066cc">PMID 18421352</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+complete+genome+of+an+individual+by+massively+parallel+DNA+sequencing&amp;rft.jtitle=Nature&amp;rft.aulast=Wheeler+DA%2C+Srinivasan+M%2C+Egholm+M%2C+Shen+Y%2C+Chen+L%2C+McGuire+A%2C+He+W%2C+Chen+YJ%2C+Makhijani+V%2C+Roth+GT%2C+Gomes+X%2C+Tartaro+K%2C+Niazi+F%2C+Turcotte+CL%2C+Irzyk+GP%2C+Lupski+JR%2C+Chinault+C%2C+Song+XZ%2C+Liu+Y%2C+Yuan+Y%2C+Nazareth+L%2C+Qin+X%2C+Muzny+DM%2C+Margulies+M%2C+Weinstock+GM%2C+Gibbs+RA%2C+Rothberg+JM.&amp;rft.au=Wheeler+DA%2C+Srinivasan+M%2C+Egholm+M%2C+Shen+Y%2C+Chen+L%2C+McGuire+A%2C+He+W%2C+Chen+YJ%2C+Makhijani+V%2C+Roth+GT%2C+Gomes+X%2C+Tartaro+K%2C+Niazi+F%2C+Turcotte+CL%2C+Irzyk+GP%2C+Lupski+JR%2C+Chinault+C%2C+Song+XZ%2C+Liu+Y%2C+Yuan+Y%2C+Nazareth+L%2C+Qin+X%2C+Muzny+DM%2C+Margulies+M%2C+Weinstock+GM%2C+Gibbs+RA%2C+Rothberg+JM.&amp;rft.date=2008&amp;rft.volume=452&amp;rft.pages=872%E2%80%936.&amp;rft_id=info:pmid/18421352&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-9"><strong><a href="#cite_ref-9"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWang_J.2C_et_al.2008">Wang J, et al. (2008). &quot;The diploid genome sequence of an Asian individual&quot;. <em>Nature</em> <strong>456</strong>: 60&ndash;65. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/18987735" href="http://www.ncbi.nlm.nih.gov/pubmed/18987735"><font color="#0066cc">PMID 18987735</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+diploid+genome+sequence+of+an+Asian+individual&amp;rft.jtitle=Nature&amp;rft.aulast=Wang+J%2C+et+al.&amp;rft.au=Wang+J%2C+et+al.&amp;rft.date=2008&amp;rft.volume=456&amp;rft.pages=60%E2%80%9365&amp;rft_id=info:pmid/18987735&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-9"><strong><a href="#cite_ref-9"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFWang_J.2C_et_al.2008">Wang J, et al. (2008). &quot;The diploid genome sequence of an Asian individual&quot;. <em>Nature</em> <strong>456</strong>: 60&ndash;65. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/18987735" href="http://www.ncbi.nlm.nih.gov/pubmed/18987735"><font color="#0066cc">PMID 18987735</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+diploid+genome+sequence+of+an+Asian+individual&amp;rft.jtitle=Nature&amp;rft.aulast=Wang+J%2C+et+al.&amp;rft.au=Wang+J%2C+et+al.&amp;rft.date=2008&amp;rft.volume=456&amp;rft.pages=60%E2%80%9365&amp;rft_id=info:pmid/18987735&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-11"><strong><a href="#cite_ref-11"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFLey_TJ.2C_Mardis_ER.2C_Ding_L.2C_Fulton_B.2C_McLellan_MD.2C_Chen_K.2C_Dooling_D.2C_Dunford-Shore_BH.2C_McGrath_S.2C_Hickenbotham_M.2C_Cook_L.2C_Abbott_R.2C_Larson_DE.2C_Koboldt.0ADC.2C_Pohl_C.2C_Smith_S.2C_Hawkins_A.2C_Abbott_S.2C_Locke_D.2C_Hillier_LW.2C_Miner_T.2C_Fulton_L.2C.0AMagrini_V.2C_Wylie_T.2C_Glasscock_J.2C_Conyers_J.2C_Sander_N.2C_Shi_X.2C_Osborne_JR.2C_Minx_P.2C_.0AGordon_D.2C_Chinwalla_A.2C_Zhao_Y.2C_Ries_RE.2C_Payton_JE.2C_Westervelt_P.2C_Tomasson_MH.2C.0AWatson_M.2C_Baty_J.2C_Ivanovich_J.2C_Heath_S.2C_Shannon_WD.2C_Nagarajan_R.2C_Walter_MJ.2C_Link_.0ADC.2C_Graubert_TA.2C_DiPersio_JF.2C_Wilson_RK.2008">Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK. (2008). &quot;DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome&quot;. <em>Nature</em> <strong>456</strong>: 66&ndash;72. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/18987736" href="http://www.ncbi.nlm.nih.gov/pubmed/18987736"><font color="#0066cc">PMID 18987736</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=DNA+sequencing+of+a+cytogenetically+normal+acute+myeloid+leukaemia+genome&amp;rft.jtitle=Nature&amp;rft.aulast=Ley+TJ%2C+Mardis+ER%2C+Ding+L%2C+Fulton+B%2C+McLellan+MD%2C+Chen+K%2C+Dooling+D%2C+Dunford-Shore+BH%2C+McGrath+S%2C+Hickenbotham+M%2C+Cook+L%2C+Abbott+R%2C+Larson+DE%2C+Koboldt%0ADC%2C+Pohl+C%2C+Smith+S%2C+Hawkins+A%2C+Abbott+S%2C+Locke+D%2C+Hillier+LW%2C+Miner+T%2C+Fulton+L%2C%0AMagrini+V%2C+Wylie+T%2C+Glasscock+J%2C+Conyers+J%2C+Sander+N%2C+Shi+X%2C+Osborne+JR%2C+Minx+P%2C+%0AGordon+D%2C+Chinwalla+A%2C+Zhao+Y%2C+Ries+RE%2C+Payton+JE%2C+Westervelt+P%2C+Tomasson+MH%2C%0AWatson+M%2C+Baty+J%2C+Ivanovich+J%2C+Heath+S%2C+Shannon+WD%2C+Nagarajan+R%2C+Walter+MJ%2C+Link+%0ADC%2C+Graubert+TA%2C+DiPersio+JF%2C+Wilson+RK.&amp;rft.au=Ley+TJ%2C+Mardis+ER%2C+Ding+L%2C+Fulton+B%2C+McLellan+MD%2C+Chen+K%2C+Dooling+D%2C+Dunford-Shore+BH%2C+McGrath+S%2C+Hickenbotham+M%2C+Cook+L%2C+Abbott+R%2C+Larson+DE%2C+Koboldt%0ADC%2C+Pohl+C%2C+Smith+S%2C+Hawkins+A%2C+Abbott+S%2C+Locke+D%2C+Hillier+LW%2C+Miner+T%2C+Fulton+L%2C%0AMagrini+V%2C+Wylie+T%2C+Glasscock+J%2C+Conyers+J%2C+Sander+N%2C+Shi+X%2C+Osborne+JR%2C+Minx+P%2C+%0AGordon+D%2C+Chinwalla+A%2C+Zhao+Y%2C+Ries+RE%2C+Payton+JE%2C+Westervelt+P%2C+Tomasson+MH%2C%0AWatson+M%2C+Baty+J%2C+Ivanovich+J%2C+Heath+S%2C+Shannon+WD%2C+Nagarajan+R%2C+Walter+MJ%2C+Link+%0ADC%2C+Graubert+TA%2C+DiPersio+JF%2C+Wilson+RK.&amp;rft.date=2008&amp;rft.volume=456&amp;rft.pages=66%E2%80%9372&amp;rft_id=info:pmid/18987736&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-11"><strong><a href="#cite_ref-11"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFLey_TJ.2C_Mardis_ER.2C_Ding_L.2C_Fulton_B.2C_McLellan_MD.2C_Chen_K.2C_Dooling_D.2C_Dunford-Shore_BH.2C_McGrath_S.2C_Hickenbotham_M.2C_Cook_L.2C_Abbott_R.2C_Larson_DE.2C_Koboldt.0ADC.2C_Pohl_C.2C_Smith_S.2C_Hawkins_A.2C_Abbott_S.2C_Locke_D.2C_Hillier_LW.2C_Miner_T.2C_Fulton_L.2C.0AMagrini_V.2C_Wylie_T.2C_Glasscock_J.2C_Conyers_J.2C_Sander_N.2C_Shi_X.2C_Osborne_JR.2C_Minx_P.2C_.0AGordon_D.2C_Chinwalla_A.2C_Zhao_Y.2C_Ries_RE.2C_Payton_JE.2C_Westervelt_P.2C_Tomasson_MH.2C.0AWatson_M.2C_Baty_J.2C_Ivanovich_J.2C_Heath_S.2C_Shannon_WD.2C_Nagarajan_R.2C_Walter_MJ.2C_Link_.0ADC.2C_Graubert_TA.2C_DiPersio_JF.2C_Wilson_RK.2008">Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK. (2008). &quot;DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome&quot;. <em>Nature</em> <strong>456</strong>: 66&ndash;72. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/18987736" href="http://www.ncbi.nlm.nih.gov/pubmed/18987736"><font color="#0066cc">PMID 18987736</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=DNA+sequencing+of+a+cytogenetically+normal+acute+myeloid+leukaemia+genome&amp;rft.jtitle=Nature&amp;rft.aulast=Ley+TJ%2C+Mardis+ER%2C+Ding+L%2C+Fulton+B%2C+McLellan+MD%2C+Chen+K%2C+Dooling+D%2C+Dunford-Shore+BH%2C+McGrath+S%2C+Hickenbotham+M%2C+Cook+L%2C+Abbott+R%2C+Larson+DE%2C+Koboldt%0ADC%2C+Pohl+C%2C+Smith+S%2C+Hawkins+A%2C+Abbott+S%2C+Locke+D%2C+Hillier+LW%2C+Miner+T%2C+Fulton+L%2C%0AMagrini+V%2C+Wylie+T%2C+Glasscock+J%2C+Conyers+J%2C+Sander+N%2C+Shi+X%2C+Osborne+JR%2C+Minx+P%2C+%0AGordon+D%2C+Chinwalla+A%2C+Zhao+Y%2C+Ries+RE%2C+Payton+JE%2C+Westervelt+P%2C+Tomasson+MH%2C%0AWatson+M%2C+Baty+J%2C+Ivanovich+J%2C+Heath+S%2C+Shannon+WD%2C+Nagarajan+R%2C+Walter+MJ%2C+Link+%0ADC%2C+Graubert+TA%2C+DiPersio+JF%2C+Wilson+RK.&amp;rft.au=Ley+TJ%2C+Mardis+ER%2C+Ding+L%2C+Fulton+B%2C+McLellan+MD%2C+Chen+K%2C+Dooling+D%2C+Dunford-Shore+BH%2C+McGrath+S%2C+Hickenbotham+M%2C+Cook+L%2C+Abbott+R%2C+Larson+DE%2C+Koboldt%0ADC%2C+Pohl+C%2C+Smith+S%2C+Hawkins+A%2C+Abbott+S%2C+Locke+D%2C+Hillier+LW%2C+Miner+T%2C+Fulton+L%2C%0AMagrini+V%2C+Wylie+T%2C+Glasscock+J%2C+Conyers+J%2C+Sander+N%2C+Shi+X%2C+Osborne+JR%2C+Minx+P%2C+%0AGordon+D%2C+Chinwalla+A%2C+Zhao+Y%2C+Ries+RE%2C+Payton+JE%2C+Westervelt+P%2C+Tomasson+MH%2C%0AWatson+M%2C+Baty+J%2C+Ivanovich+J%2C+Heath+S%2C+Shannon+WD%2C+Nagarajan+R%2C+Walter+MJ%2C+Link+%0ADC%2C+Graubert+TA%2C+DiPersio+JF%2C+Wilson+RK.&amp;rft.date=2008&amp;rft.volume=456&amp;rft.pages=66%E2%80%9372&amp;rft_id=info:pmid/18987736&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-12"><strong><a href="#cite_ref-12"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFAhn_SM.2C_Kim_TH.2C_Lee_S.2C_Kim_D.2C_Ghang_H.2C_Kim_D.2C_Kim_BC.2C_Kim_SY.2C_Kim_WY.2C_Kim_C.2C_Park_D.2C_Lee_YS.2C_Kim_S.2C_Reja_R.2C_Jho_S.2C_Kim_CG.2C_Cha_JY.2C_Kim_KH.2C_Lee_B.2C_Bhak_J.2C_Kim_SJ2009">Ahn SM, Kim TH, Lee S, Kim D, Ghang H, Kim D, Kim BC, Kim SY, Kim WY, Kim C, Park D, Lee YS, Kim S, Reja R, Jho S, Kim CG, Cha JY, Kim KH, Lee B, Bhak J, Kim SJ (2009). &quot;The first Korean genome sequence and analysis: Full genome sequencing for a socio-ethnic group&quot;. <em>Genome Research</em>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/19470904" href="http://www.ncbi.nlm.nih.gov/pubmed/19470904"><font color="#0066cc">PMID 19470904</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+first+Korean+genome+sequence+and+analysis%3A+Full+genome+sequencing+for+a%0Asocio-ethnic+group&amp;rft.jtitle=Genome+Research&amp;rft.aulast=Ahn+SM%2C+Kim+TH%2C+Lee+S%2C+Kim+D%2C+Ghang+H%2C+Kim+D%2C+Kim+BC%2C+Kim+SY%2C+Kim+WY%2C+Kim+C%2C+Park+D%2C+Lee+YS%2C+Kim+S%2C+Reja+R%2C+Jho+S%2C+Kim+CG%2C+Cha+JY%2C+Kim+KH%2C+Lee+B%2C+Bhak+J%2C+Kim+SJ&amp;rft.au=Ahn+SM%2C+Kim+TH%2C+Lee+S%2C+Kim+D%2C+Ghang+H%2C+Kim+D%2C+Kim+BC%2C+Kim+SY%2C+Kim+WY%2C+Kim+C%2C+Park+D%2C+Lee+YS%2C+Kim+S%2C+Reja+R%2C+Jho+S%2C+Kim+CG%2C+Cha+JY%2C+Kim+KH%2C+Lee+B%2C+Bhak+J%2C+Kim+SJ&amp;rft.date=2009&amp;rft_id=info:pmid/19470904&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-12"><strong><a href="#cite_ref-12"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFAhn_SM.2C_Kim_TH.2C_Lee_S.2C_Kim_D.2C_Ghang_H.2C_Kim_D.2C_Kim_BC.2C_Kim_SY.2C_Kim_WY.2C_Kim_C.2C_Park_D.2C_Lee_YS.2C_Kim_S.2C_Reja_R.2C_Jho_S.2C_Kim_CG.2C_Cha_JY.2C_Kim_KH.2C_Lee_B.2C_Bhak_J.2C_Kim_SJ2009">Ahn SM, Kim TH, Lee S, Kim D, Ghang H, Kim D, Kim BC, Kim SY, Kim WY, Kim C, Park D, Lee YS, Kim S, Reja R, Jho S, Kim CG, Cha JY, Kim KH, Lee B, Bhak J, Kim SJ (2009). &quot;The first Korean genome sequence and analysis: Full genome sequencing for a socio-ethnic group&quot;. <em>Genome Research</em>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/19470904" href="http://www.ncbi.nlm.nih.gov/pubmed/19470904"><font color="#0066cc">PMID 19470904</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+first+Korean+genome+sequence+and+analysis%3A+Full+genome+sequencing+for+a%0Asocio-ethnic+group&amp;rft.jtitle=Genome+Research&amp;rft.aulast=Ahn+SM%2C+Kim+TH%2C+Lee+S%2C+Kim+D%2C+Ghang+H%2C+Kim+D%2C+Kim+BC%2C+Kim+SY%2C+Kim+WY%2C+Kim+C%2C+Park+D%2C+Lee+YS%2C+Kim+S%2C+Reja+R%2C+Jho+S%2C+Kim+CG%2C+Cha+JY%2C+Kim+KH%2C+Lee+B%2C+Bhak+J%2C+Kim+SJ&amp;rft.au=Ahn+SM%2C+Kim+TH%2C+Lee+S%2C+Kim+D%2C+Ghang+H%2C+Kim+D%2C+Kim+BC%2C+Kim+SY%2C+Kim+WY%2C+Kim+C%2C+Park+D%2C+Lee+YS%2C+Kim+S%2C+Reja+R%2C+Jho+S%2C+Kim+CG%2C+Cha+JY%2C+Kim+KH%2C+Lee+B%2C+Bhak+J%2C+Kim+SJ&amp;rft.date=2009&amp;rft_id=info:pmid/19470904&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-13"><strong><a href="#cite_ref-13"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="web">&quot;<a class="external text" title="http://www.nanotechwire.com/news.asp?nid=6428" href="http://www.nanotechwire.com/news.asp?nid=6428" rel="nofollow"><font color="#0066cc">Harvard University and Oxford Nanopore Technologies Announce Licence Agreement to Advance Nanopore DNA Sequencing and other Applications</font></a>&quot;. Nanotechwire. August 5, 2008<span class="printonly">. <a class="external free" title="http://www.nanotechwire.com/news.asp?nid=6428" href="http://www.nanotechwire.com/news.asp?nid=6428" rel="nofollow"><font color="#0066cc">http://www.nanotechwire.com/news.asp?nid=6428</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Harvard+University+and+Oxford+Nanopore+Technologies+Announce+Licence+Agreement+to+Advance+Nanopore+DNA+Sequencing+and+other+Applications&amp;rft.atitle=&amp;rft.date=August+5%2C+2008&amp;rft.pub=Nanotechwire&amp;rft_id=http%3A%2F%2Fwww.nanotechwire.com%2Fnews.asp%3Fnid%3D6428&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-13"><strong><a href="#cite_ref-13"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="web">&quot;<a class="external text" title="http://www.nanotechwire.com/news.asp?nid=6428" rel="nofollow" href="http://www.nanotechwire.com/news.asp?nid=6428"><font color="#0066cc">Harvard University and Oxford Nanopore Technologies Announce Licence Agreement to Advance Nanopore DNA Sequencing and other Applications</font></a>&quot;. Nanotechwire. August 5, 2008<span class="printonly">. <a class="external free" title="http://www.nanotechwire.com/news.asp?nid=6428" rel="nofollow" href="http://www.nanotechwire.com/news.asp?nid=6428"><font color="#0066cc">http://www.nanotechwire.com/news.asp?nid=6428</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Harvard+University+and+Oxford+Nanopore+Technologies+Announce+Licence+Agreement+to+Advance+Nanopore+DNA+Sequencing+and+other+Applications&amp;rft.atitle=&amp;rft.date=August+5%2C+2008&amp;rft.pub=Nanotechwire&amp;rft_id=http%3A%2F%2Fwww.nanotechwire.com%2Fnews.asp%3Fnid%3D6428&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-14"><strong><a href="#cite_ref-14"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="news">&quot;<a class="external text" title="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112" href="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112" rel="nofollow"><font color="#0066cc">Illumina and Oxford Nanopore Enter into Broad Commercialization Agreement</font></a>&quot;. Reuters. January 12, 2009<span class="printonly">. <a class="external free" title="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112" href="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112" rel="nofollow"><font color="#0066cc">http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Illumina+and+Oxford+Nanopore+Enter+into+Broad+Commercialization+Agreement&amp;rft.atitle=&amp;rft.date=January+12%2C+2009&amp;rft.pub=Reuters&amp;rft_id=http%3A%2F%2Fwww.reuters.com%2Farticle%2FpressRelease%2FidUS49869%2B12-Jan-2009%2BBW20090112&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-14"><strong><a href="#cite_ref-14"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="news">&quot;<a class="external text" title="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112" rel="nofollow" href="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112"><font color="#0066cc">Illumina and Oxford Nanopore Enter into Broad Commercialization Agreement</font></a>&quot;. Reuters. January 12, 2009<span class="printonly">. <a class="external free" title="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112" rel="nofollow" href="http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112"><font color="#0066cc">http://www.reuters.com/article/pressRelease/idUS49869+12-Jan-2009+BW20090112</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Illumina+and+Oxford+Nanopore+Enter+into+Broad+Commercialization+Agreement&amp;rft.atitle=&amp;rft.date=January+12%2C+2009&amp;rft.pub=Reuters&amp;rft_id=http%3A%2F%2Fwww.reuters.com%2Farticle%2FpressRelease%2FidUS49869%2B12-Jan-2009%2BBW20090112&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-15"><strong><a href="#cite_ref-15"><font color="#0066cc">^</font></a></strong> <a class="external free" title="http://www..com/sequenom-licenses-nanopore-technology-harvard-develop-third-generation-sequencer" href="http://www..com/sequenom-licenses-nanopore-technology-harvard-develop-third-generation-sequencer" rel="nofollow"><font color="#0066cc">http://www..com/sequenom-licenses-nanopore-technology-harvard-develop-third-generation-sequencer</font></a></li>
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     <li id="cite_note-15"><strong><a href="#cite_ref-15"><font color="#0066cc">^</font></a></strong> <a class="external free" title="http://www..com/sequenom-licenses-nanopore-technology-harvard-develop-third-generation-sequencer" rel="nofollow" href="http://www..com/sequenom-licenses-nanopore-technology-harvard-develop-third-generation-sequencer"><font color="#0066cc">http://www..com/sequenom-licenses-nanopore-technology-harvard-develop-third-generation-sequencer</font></a></li>
     <li id="cite_note-16"><strong><a href="#cite_ref-16"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="news">&quot;<a class="external text" title="http://www.pacificbiosciences.com/index.php?q=technology-introduction" href="http://www.pacificbiosciences.com/index.php?q=technology-introduction" rel="nofollow"><font color="#0066cc">Single Molecule Real Time (SMRT) DNA Sequencing</font></a>&quot;. Pacific Biosciences<span class="printonly">. <a class="external free" title="http://www.pacificbiosciences.com/index.php?q=technology-introduction" href="http://www.pacificbiosciences.com/index.php?q=technology-introduction" rel="nofollow"><font color="#0066cc">http://www.pacificbiosciences.com/index.php?q=technology-introduction</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Single+Molecule+Real+Time+%28SMRT%29+DNA+Sequencing&amp;rft.atitle=&amp;rft.pub=Pacific+Biosciences&amp;rft_id=http%3A%2F%2Fwww.pacificbiosciences.com%2Findex.php%3Fq%3Dtechnology-introduction&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-16"><strong><a href="#cite_ref-16"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="news">&quot;<a class="external text" title="http://www.pacificbiosciences.com/index.php?q=technology-introduction" rel="nofollow" href="http://www.pacificbiosciences.com/index.php?q=technology-introduction"><font color="#0066cc">Single Molecule Real Time (SMRT) DNA Sequencing</font></a>&quot;. Pacific Biosciences<span class="printonly">. <a class="external free" title="http://www.pacificbiosciences.com/index.php?q=technology-introduction" rel="nofollow" href="http://www.pacificbiosciences.com/index.php?q=technology-introduction"><font color="#0066cc">http://www.pacificbiosciences.com/index.php?q=technology-introduction</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Single+Molecule+Real+Time+%28SMRT%29+DNA+Sequencing&amp;rft.atitle=&amp;rft.pub=Pacific+Biosciences&amp;rft_id=http%3A%2F%2Fwww.pacificbiosciences.com%2Findex.php%3Fq%3Dtechnology-introduction&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-17"><strong><a href="#cite_ref-17"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="news">&quot;<a class="external text" title="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf" href="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf" rel="nofollow"><font color="#0066cc">Complete Human Genome Sequencing Technology Overview</font></a>&quot;. Complete Genomics. 2009<span class="printonly">. <a class="external free" title="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf" href="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf" rel="nofollow"><font color="#0066cc">http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Complete+Human+Genome+Sequencing+Technology+Overview&amp;rft.atitle=&amp;rft.date=2009&amp;rft.pub=Complete+Genomics&amp;rft_id=http%3A%2F%2Fwww.completegenomicsinc.com%2Fpages%2Fmaterials%2FCompleteGenomicsTechnologyPaper.pdf&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-17"><strong><a href="#cite_ref-17"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="news">&quot;<a class="external text" title="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf" rel="nofollow" href="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf"><font color="#0066cc">Complete Human Genome Sequencing Technology Overview</font></a>&quot;. Complete Genomics. 2009<span class="printonly">. <a class="external free" title="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf" rel="nofollow" href="http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf"><font color="#0066cc">http://www.completegenomicsinc.com/pages/materials/CompleteGenomicsTechnologyPaper.pdf</font></a></span><span class="reference-accessdate">. Retrieved on February 23, 2009</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Complete+Human+Genome+Sequencing+Technology+Overview&amp;rft.atitle=&amp;rft.date=2009&amp;rft.pub=Complete+Genomics&amp;rft_id=http%3A%2F%2Fwww.completegenomicsinc.com%2Fpages%2Fmaterials%2FCompleteGenomicsTechnologyPaper.pdf&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-18"><strong><a href="#cite_ref-18"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="web">&quot;<a class="external text" title="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html" href="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html" rel="nofollow"><font color="#0066cc">Definition of pyrosequencing from the Nature Reviews Genetics Glossary</font></a>&quot;<span class="printonly">. <a class="external free" title="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html" href="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html" rel="nofollow"><font color="#0066cc">http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html</font></a></span><span class="reference-accessdate">. Retrieved on 2008-10-28</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Definition+of+pyrosequencing+from+the+Nature+Reviews+Genetics+Glossary&amp;rft.atitle=&amp;rft_id=http%3A%2F%2Fwww.nature.com%2Fnrg%2Fjournal%2Fv6%2Fn11%2Fglossary%2Fnrg1709_glossary.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-18"><strong><a href="#cite_ref-18"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" class="web">&quot;<a class="external text" title="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html" rel="nofollow" href="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html"><font color="#0066cc">Definition of pyrosequencing from the Nature Reviews Genetics Glossary</font></a>&quot;<span class="printonly">. <a class="external free" title="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html" rel="nofollow" href="http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html"><font color="#0066cc">http://www.nature.com/nrg/journal/v6/n11/glossary/nrg1709_glossary.html</font></a></span><span class="reference-accessdate">. Retrieved on 2008-10-28</span>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&amp;rft.genre=bookitem&amp;rft.btitle=Definition+of+pyrosequencing+from+the+Nature+Reviews+Genetics+Glossary&amp;rft.atitle=&amp;rft_id=http%3A%2F%2Fwww.nature.com%2Fnrg%2Fjournal%2Fv6%2Fn11%2Fglossary%2Fnrg1709_glossary.html&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-RonachiScience-19"><strong><a href="#cite_ref-RonachiScience_19-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFRonaghi_M.2C_Uhl.C3.A9n_M.2C_Nyr.C3.A9n_P1998">Ronaghi M, Uhl&eacute;n M, Nyr&eacute;n P (July 1998). &quot;A sequencing method based on real-time pyrophosphate&quot;. <em>Science (journal)</em> <strong>281</strong> (5375): 363, 365. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1126%2Fscience.281.5375.363" href="http://dx.doi.org/10.1126%2Fscience.281.5375.363" rel="nofollow"><font color="#0066cc">10.1126/science.281.5375.363</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/9705713" href="http://www.ncbi.nlm.nih.gov/pubmed/9705713"><font color="#0066cc">PMID 9705713</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=A+sequencing+method+based+on+real-time+pyrophosphate&amp;rft.jtitle=Science+%28journal%29&amp;rft.aulast=Ronaghi+M%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.au=Ronaghi+M%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.date=July+1998&amp;rft.volume=281&amp;rft.issue=5375&amp;rft.pages=363%2C+365&amp;rft_id=info:doi/10.1126%2Fscience.281.5375.363&amp;rft_id=info:pmid/9705713&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
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     <li id="cite_note-RonachiScience-19"><strong><a href="#cite_ref-RonachiScience_19-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFRonaghi_M.2C_Uhl.C3.A9n_M.2C_Nyr.C3.A9n_P1998">Ronaghi M, Uhl&eacute;n M, Nyr&eacute;n P (July 1998). &quot;A sequencing method based on real-time pyrophosphate&quot;. <em>Science (journal)</em> <strong>281</strong> (5375): 363, 365. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1126%2Fscience.281.5375.363" rel="nofollow" href="http://dx.doi.org/10.1126%2Fscience.281.5375.363"><font color="#0066cc">10.1126/science.281.5375.363</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/9705713" href="http://www.ncbi.nlm.nih.gov/pubmed/9705713"><font color="#0066cc">PMID 9705713</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=A+sequencing+method+based+on+real-time+pyrophosphate&amp;rft.jtitle=Science+%28journal%29&amp;rft.aulast=Ronaghi+M%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.au=Ronaghi+M%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.date=July+1998&amp;rft.volume=281&amp;rft.issue=5375&amp;rft.pages=363%2C+365&amp;rft_id=info:doi/10.1126%2Fscience.281.5375.363&amp;rft_id=info:pmid/9705713&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-pmid8923969-20"><strong><a href="#cite_ref-pmid8923969_20-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFRonaghi_M.2C_Karamohamed_S.2C_Pettersson_B.2C_Uhl.C3.A9n_M.2C_Nyr.C3.A9n_P1996">Ronaghi M, Karamohamed S, Pettersson B, Uhl&eacute;n M, Nyr&eacute;n P (November 1996). &quot;Real-time DNA sequencing using detection of pyrophosphate release&quot;. <em>Anal. Biochem.</em> <strong>242</strong> (1): 84&ndash;9. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1006%2Fabio.1996.0432" href="http://dx.doi.org/10.1006%2Fabio.1996.0432" rel="nofollow"><font color="#0066cc">10.1006/abio.1996.0432</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/8923969" href="http://www.ncbi.nlm.nih.gov/pubmed/8923969"><font color="#0066cc">PMID 8923969</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Real-time+DNA+sequencing+using+detection+of+pyrophosphate+release&amp;rft.jtitle=Anal.+Biochem.&amp;rft.aulast=Ronaghi+M%2C+Karamohamed+S%2C+Pettersson+B%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.au=Ronaghi+M%2C+Karamohamed+S%2C+Pettersson+B%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.date=November+1996&amp;rft.volume=242&amp;rft.issue=1&amp;rft.pages=84%E2%80%939&amp;rft_id=info:doi/10.1006%2Fabio.1996.0432&amp;rft_id=info:pmid/8923969&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
+
     <li id="cite_note-pmid8923969-20"><strong><a href="#cite_ref-pmid8923969_20-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFRonaghi_M.2C_Karamohamed_S.2C_Pettersson_B.2C_Uhl.C3.A9n_M.2C_Nyr.C3.A9n_P1996">Ronaghi M, Karamohamed S, Pettersson B, Uhl&eacute;n M, Nyr&eacute;n P (November 1996). &quot;Real-time DNA sequencing using detection of pyrophosphate release&quot;. <em>Anal. Biochem.</em> <strong>242</strong> (1): 84&ndash;9. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1006%2Fabio.1996.0432" rel="nofollow" href="http://dx.doi.org/10.1006%2Fabio.1996.0432"><font color="#0066cc">10.1006/abio.1996.0432</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/8923969" href="http://www.ncbi.nlm.nih.gov/pubmed/8923969"><font color="#0066cc">PMID 8923969</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Real-time+DNA+sequencing+using+detection+of+pyrophosphate+release&amp;rft.jtitle=Anal.+Biochem.&amp;rft.aulast=Ronaghi+M%2C+Karamohamed+S%2C+Pettersson+B%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.au=Ronaghi+M%2C+Karamohamed+S%2C+Pettersson+B%2C+Uhl%C3%A9n+M%2C+Nyr%C3%A9n+P&amp;rft.date=November+1996&amp;rft.volume=242&amp;rft.issue=1&amp;rft.pages=84%E2%80%939&amp;rft_id=info:doi/10.1006%2Fabio.1996.0432&amp;rft_id=info:pmid/8923969&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-pmid17185753-21"><strong><a href="#cite_ref-pmid17185753_21-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFNyr.C3.A9n_P2007">Nyr&eacute;n P (2007). &quot;The history of pyrosequencing&quot;. <em>Methods Mol. Biol.</em> <strong>373</strong>: 1&ndash;14. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17185753" href="http://www.ncbi.nlm.nih.gov/pubmed/17185753"><font color="#0066cc">PMID 17185753</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+history+of+pyrosequencing&amp;rft.jtitle=Methods+Mol.+Biol.&amp;rft.aulast=Nyr%C3%A9n+P&amp;rft.au=Nyr%C3%A9n+P&amp;rft.date=2007&amp;rft.volume=373&amp;rft.pages=1%E2%80%9314&amp;rft_id=info:pmid/17185753&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-pmid17185753-21"><strong><a href="#cite_ref-pmid17185753_21-0"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFNyr.C3.A9n_P2007">Nyr&eacute;n P (2007). &quot;The history of pyrosequencing&quot;. <em>Methods Mol. Biol.</em> <strong>373</strong>: 1&ndash;14. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17185753" href="http://www.ncbi.nlm.nih.gov/pubmed/17185753"><font color="#0066cc">PMID 17185753</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=The+history+of+pyrosequencing&amp;rft.jtitle=Methods+Mol.+Biol.&amp;rft.aulast=Nyr%C3%A9n+P&amp;rft.au=Nyr%C3%A9n+P&amp;rft.date=2007&amp;rft.volume=373&amp;rft.pages=1%E2%80%9314&amp;rft_id=info:pmid/17185753&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
    <li id="cite_note-22"><strong><a href="#cite_ref-22"><font color="#0066cc">^</font></a></strong> <
+
    <li id="cite_note-22"><strong><a href="#cite_ref-22"><font color="#0066cc">^</font></a></strong> <
 
     <li id="cite_note-70"><strong><a href="#cite_ref-70"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFMcCabe_LL.2C_McCabe_ER2001">McCabe LL, McCabe ER (June 2001). &quot;Postgenomic medicine. Presymptomatic testing for prediction and prevention&quot;. <em>Clin Perinatol</em> <strong>28</strong> (2): 425&ndash;34. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/11499063" href="http://www.ncbi.nlm.nih.gov/pubmed/11499063"><font color="#0066cc">PMID 11499063</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Postgenomic+medicine.+Presymptomatic+testing+for+prediction+and+prevention&amp;rft.jtitle=Clin+Perinatol&amp;rft.aulast=McCabe+LL%2C+McCabe+ER&amp;rft.au=McCabe+LL%2C+McCabe+ER&amp;rft.date=June+2001&amp;rft.volume=28&amp;rft.issue=2&amp;rft.pages=425%E2%80%9334&amp;rft_id=info:pmid/11499063&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-70"><strong><a href="#cite_ref-70"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFMcCabe_LL.2C_McCabe_ER2001">McCabe LL, McCabe ER (June 2001). &quot;Postgenomic medicine. Presymptomatic testing for prediction and prevention&quot;. <em>Clin Perinatol</em> <strong>28</strong> (2): 425&ndash;34. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/11499063" href="http://www.ncbi.nlm.nih.gov/pubmed/11499063"><font color="#0066cc">PMID 11499063</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Postgenomic+medicine.+Presymptomatic+testing+for+prediction+and+prevention&amp;rft.jtitle=Clin+Perinatol&amp;rft.aulast=McCabe+LL%2C+McCabe+ER&amp;rft.au=McCabe+LL%2C+McCabe+ER&amp;rft.date=June+2001&amp;rft.volume=28&amp;rft.issue=2&amp;rft.pages=425%E2%80%9334&amp;rft_id=info:pmid/11499063&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-71"><strong><a href="#cite_ref-71"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFNelson_RM.2C_Botkjin_JR.2C_Kodish_ED.2C_.27.27et_al..27.272001">Nelson RM, Botkjin JR, Kodish ED, <em>et al.</em> (June 2001). &quot;Ethical issues with genetic testing in pediatrics&quot;. <em>Pediatrics</em> <strong>107</strong> (6): 1451&ndash;5. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/11389275" href="http://www.ncbi.nlm.nih.gov/pubmed/11389275"><font color="#0066cc">PMID 11389275</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Ethical+issues+with+genetic+testing+in+pediatrics&amp;rft.jtitle=Pediatrics&amp;rft.aulast=Nelson+RM%2C+Botkjin+JR%2C+Kodish+ED%2C+%27%27et+al.%27%27&amp;rft.au=Nelson+RM%2C+Botkjin+JR%2C+Kodish+ED%2C+%27%27et+al.%27%27&amp;rft.date=June+2001&amp;rft.volume=107&amp;rft.issue=6&amp;rft.pages=1451%E2%80%935&amp;rft_id=info:pmid/11389275&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
     <li id="cite_note-71"><strong><a href="#cite_ref-71"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFNelson_RM.2C_Botkjin_JR.2C_Kodish_ED.2C_.27.27et_al..27.272001">Nelson RM, Botkjin JR, Kodish ED, <em>et al.</em> (June 2001). &quot;Ethical issues with genetic testing in pediatrics&quot;. <em>Pediatrics</em> <strong>107</strong> (6): 1451&ndash;5. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/11389275" href="http://www.ncbi.nlm.nih.gov/pubmed/11389275"><font color="#0066cc">PMID 11389275</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Ethical+issues+with+genetic+testing+in+pediatrics&amp;rft.jtitle=Pediatrics&amp;rft.aulast=Nelson+RM%2C+Botkjin+JR%2C+Kodish+ED%2C+%27%27et+al.%27%27&amp;rft.au=Nelson+RM%2C+Botkjin+JR%2C+Kodish+ED%2C+%27%27et+al.%27%27&amp;rft.date=June+2001&amp;rft.volume=107&amp;rft.issue=6&amp;rft.pages=1451%E2%80%935&amp;rft_id=info:pmid/11389275&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-72"><strong><a href="#cite_ref-72"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFBorry_P.2C_Fryns_JP.2C_Schotsmans_P.2C_Dierickx_K2006">Borry P, Fryns JP, Schotsmans P, Dierickx K (February 2006). &quot;Carrier testing in minors: a systematic review of guidelines and position papers&quot;. <em>Eur. J. Hum. Genet.</em> <strong>14</strong> (2): 133&ndash;8. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1038%2Fsj.ejhg.5201509" href="http://dx.doi.org/10.1038%2Fsj.ejhg.5201509" rel="nofollow"><font color="#0066cc">10.1038/sj.ejhg.5201509</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/16267502" href="http://www.ncbi.nlm.nih.gov/pubmed/16267502"><font color="#0066cc">PMID 16267502</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Carrier+testing+in+minors%3A+a+systematic+review+of+guidelines+and+position+papers&amp;rft.jtitle=Eur.+J.+Hum.+Genet.&amp;rft.aulast=Borry+P%2C+Fryns+JP%2C+Schotsmans+P%2C+Dierickx+K&amp;rft.au=Borry+P%2C+Fryns+JP%2C+Schotsmans+P%2C+Dierickx+K&amp;rft.date=February+2006&amp;rft.volume=14&amp;rft.issue=2&amp;rft.pages=133%E2%80%938&amp;rft_id=info:doi/10.1038%2Fsj.ejhg.5201509&amp;rft_id=info:pmid/16267502&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
+
     <li id="cite_note-72"><strong><a href="#cite_ref-72"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFBorry_P.2C_Fryns_JP.2C_Schotsmans_P.2C_Dierickx_K2006">Borry P, Fryns JP, Schotsmans P, Dierickx K (February 2006). &quot;Carrier testing in minors: a systematic review of guidelines and position papers&quot;. <em>Eur. J. Hum. Genet.</em> <strong>14</strong> (2): 133&ndash;8. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1038%2Fsj.ejhg.5201509" rel="nofollow" href="http://dx.doi.org/10.1038%2Fsj.ejhg.5201509"><font color="#0066cc">10.1038/sj.ejhg.5201509</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/16267502" href="http://www.ncbi.nlm.nih.gov/pubmed/16267502"><font color="#0066cc">PMID 16267502</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Carrier+testing+in+minors%3A+a+systematic+review+of+guidelines+and+position+papers&amp;rft.jtitle=Eur.+J.+Hum.+Genet.&amp;rft.aulast=Borry+P%2C+Fryns+JP%2C+Schotsmans+P%2C+Dierickx+K&amp;rft.au=Borry+P%2C+Fryns+JP%2C+Schotsmans+P%2C+Dierickx+K&amp;rft.date=February+2006&amp;rft.volume=14&amp;rft.issue=2&amp;rft.pages=133%E2%80%938&amp;rft_id=info:doi/10.1038%2Fsj.ejhg.5201509&amp;rft_id=info:pmid/16267502&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
     <li id="cite_note-73"><strong><a href="#cite_ref-73"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFBorry_P.2C_Stultiens_L.2C_Nys_H.2C_Cassiman_JJ.2C_Dierickx_K2006">Borry P, Stultiens L, Nys H, Cassiman JJ, Dierickx K (November 2006). &quot;Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers&quot;. <em>Clin. Genet.</em> <strong>70</strong> (5): 374&ndash;81. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1111%2Fj.1399-0004.2006.00692.x" href="http://dx.doi.org/10.1111%2Fj.1399-0004.2006.00692.x" rel="nofollow"><font color="#0066cc">10.1111/j.1399-0004.2006.00692.x</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17026616" href="http://www.ncbi.nlm.nih.gov/pubmed/17026616"><font color="#0066cc">PMID 17026616</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Presymptomatic+and+predictive+genetic+testing+in+minors%3A+a+systematic+review+of+guidelines+and+position+papers&amp;rft.jtitle=Clin.+Genet.&amp;rft.aulast=Borry+P%2C+Stultiens+L%2C+Nys+H%2C+Cassiman+JJ%2C+Dierickx+K&amp;rft.au=Borry+P%2C+Stultiens+L%2C+Nys+H%2C+Cassiman+JJ%2C+Dierickx+K&amp;rft.date=November+2006&amp;rft.volume=70&amp;rft.issue=5&amp;rft.pages=374%E2%80%9381&amp;rft_id=info:doi/10.1111%2Fj.1399-0004.2006.00692.x&amp;rft_id=info:pmid/17026616&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
+
     <li id="cite_note-73"><strong><a href="#cite_ref-73"><font color="#0066cc">^</font></a></strong> <cite style="FONT-STYLE: normal" id="CITEREFBorry_P.2C_Stultiens_L.2C_Nys_H.2C_Cassiman_JJ.2C_Dierickx_K2006">Borry P, Stultiens L, Nys H, Cassiman JJ, Dierickx K (November 2006). &quot;Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers&quot;. <em>Clin. Genet.</em> <strong>70</strong> (5): 374&ndash;81. <a title="Digital object identifier" href="/wiki/Digital_object_identifier"><font color="#0066cc">doi</font></a>:<span class="neverexpand"><a class="external text" title="http://dx.doi.org/10.1111%2Fj.1399-0004.2006.00692.x" rel="nofollow" href="http://dx.doi.org/10.1111%2Fj.1399-0004.2006.00692.x"><font color="#0066cc">10.1111/j.1399-0004.2006.00692.x</font></a></span>. <a class="external" title="http://www.ncbi.nlm.nih.gov/pubmed/17026616" href="http://www.ncbi.nlm.nih.gov/pubmed/17026616"><font color="#0066cc">PMID 17026616</font></a>.</cite><span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.genre=article&amp;rft.atitle=Presymptomatic+and+predictive+genetic+testing+in+minors%3A+a+systematic+review+of+guidelines+and+position+papers&amp;rft.jtitle=Clin.+Genet.&amp;rft.aulast=Borry+P%2C+Stultiens+L%2C+Nys+H%2C+Cassiman+JJ%2C+Dierickx+K&amp;rft.au=Borry+P%2C+Stultiens+L%2C+Nys+H%2C+Cassiman+JJ%2C+Dierickx+K&amp;rft.date=November+2006&amp;rft.volume=70&amp;rft.issue=5&amp;rft.pages=374%E2%80%9381&amp;rft_id=info:doi/10.1111%2Fj.1399-0004.2006.00692.x&amp;rft_id=info:pmid/17026616&amp;rfr_id=info:sid/en.wikipedia.org:Full_genome_sequencing"><span style="DISPLAY: none">&nbsp;</span></span></li>
 
</ol>
 
</ol>
 
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<h2><span class="mw-headline">External links</span></h2>
 
<h2><span class="mw-headline">External links</span></h2>
 
<ul>
 
<ul>
     <li><a class="external text" title="http://genomics.xprize.org/" href="http://genomics.xprize.org/" rel="nofollow"><font color="#0066cc">Archon X Prize for Genomics</font></a></li>
+
     <li><a class="external text" title="http://genomics.xprize.org/" rel="nofollow" href="http://genomics.xprize.org/"><font color="#0066cc">Archon X Prize for Genomics</font></a></li>
     <li><a class="external text" title="http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/" href="http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/" rel="nofollow"><font color="#0066cc">James Watson's Personal Genome Sequence</font></a></li>
+
     <li><a class="external text" title="http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/" rel="nofollow" href="http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/"><font color="#0066cc">James Watson's Personal Genome Sequence</font></a></li>
     <li><a class="external text" title="http://www.illumina.com" href="http://www.illumina.com" rel="nofollow"><font color="#0066cc">Illumina's Website</font></a></li>
+
     <li><a class="external text" title="http://www.illumina.com" rel="nofollow" href="http://www.illumina.com"><font color="#0066cc">Illumina's Website</font></a></li>
     <li><a class="external text" title="http://www.sequenom.com" href="http://www.sequenom.com" rel="nofollow"><font color="#0066cc">Sequenom's Website</font></a></li>
+
     <li><a class="external text" title="http://www.sequenom.com" rel="nofollow" href="http://www.sequenom.com"><font color="#0066cc">Sequenom's Website</font></a></li>
     <li><a class="external text" title="http://www.454.com/" href="http://www.454.com/" rel="nofollow"><font color="#0066cc">454 Life Science's Website</font></a></li>
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     <li><a class="external text" title="http://www.454.com/" rel="nofollow" href="http://www.454.com/"><font color="#0066cc">454 Life Science's Website</font></a></li>
     <li><a class="external text" title="http://www.pacificbiosciences.com/index.php" href="http://www.pacificbiosciences.com/index.php" rel="nofollow"><font color="#0066cc">Pacific Biosciences' Website</font></a></li>
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     <li><a class="external text" title="http://www.completegenomicsinc.com/" href="http://www.completegenomicsinc.com/" rel="nofollow"><font color="#0066cc">Complete Genomics' Website</font></a></li>
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     <li><a class="external text" title="http://www.intelligentbiosystems.com/" href="http://www.intelligentbiosystems.com/" rel="nofollow"><font color="#0066cc">Intelligent Bio-System's Website</font></a></li>
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     <li><a class="external text" title="http://www.helicosbio.com/" href="http://www.helicosbio.com/" rel="nofollow"><font color="#0066cc">Helicos BioScience's Website</font></a></li>
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     <li><a class="external text" title="http://genomecorp.com/" href="http://genomecorp.com/" rel="nofollow"><font color="#0066cc">Genome Corp's Website</font></a></li>
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Latest revision as of 15:24, 23 October 2011

Full genome sequencing (FGS), also known as whole genome sequencing, complete genome sequencing, or entire genome sequencing, is a laboratory process that determines the complete DNA sequence of an organism's genome at a single time.

This entails sequencing all of an organism's chromosomal DNA as well as DNA contained in the mitochondria or chloroplast, depending respectively on whether the organism is an animal or plant. Almost any biological sample—even a very small amount of DNA or ancient DNA—can provide the genetic material necessary for full genome sequencing. Such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, 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 pairs 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, computers, and the Information Age.

Full genome sequencing should thus not be confused with DNA profiling. The latter only determines the likelihood that genetic material came from a particular individual or group and does not contain additional information on genetic relationships, origin or suspectability on specific diseases. [1]. It is also distinct from SNP genotyping which covers less than 0.1% of the genome. Almost all truly complete genomes are of microbes, the term "full genome" is sometimes used loosely to mean "greater than 95%". The remainder of this article focuses on nearly complete human genomes.

 

Full genome sequencing only refers to the laboratory process of deducing a person's entire genetic code and, on its own, may not contain any clinical assessment or useful clinical information. However, 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.[2][3]

The first nearly complete human genomes sequenced were J. Craig Venter's (caucasian male at 7.5-fold average coverage) [4][5][6] and James Watson's (caucasian male at 7.4-fold).[7][8][9], a Han Chinese (YH at 36-fold) [10], a Yoruban from Nigeria (at 30-fold) [11], a female leukemia patient (at 33 and 14-fold coverage for tumor and normal tissues)[12], and Seong-Jin Kim (Korean at 29-fold) [13]. Other full genomes have been sequenced but not published, and as of June 2009, commercialization of full genome sequencing is in an early stage and growing rapidly.

 

Genome Sequencing Procedure

 

 

New techniques

An ABI PRISM 3100 Genetic Analyzer. Sequencers automate the process of sequencing the genome.

One possible way to accomplish the cost-effective high-throughput sequencing necessary to accomplish full genome sequencing is by using Nanopore technology, which is a patented technology held by Harvard University and Oxford Nanopore Technologies and licensed to biotechnology companies.[14] To facilitate their full genome sequencing initiatives, Illumina licensed nanopore sequencing technology from Oxford Nanopore Technologies and Sequenom licensed the technology from Harvard University.[15][16] Another possible way to accomplish cost-effective high-throughput sequencing is by utilizing fluorophore technology. Pacific Biosciences is currently using this approach in their SMRT (single molecule real time) DNA sequencing technology.[17] Complete Genomics is developing DNA Nanoball (DNB) technology that are arranged on self-assembling arrays.[18] Pyrosequencing is a method of DNA sequencing based on the sequencing by synthesis principle.[19] The technique was developed by Pål Nyrén and his student Mostafa Ronaghi at the Royal Institute of Technology in Stockholm in 1996,[20][21][22] and is currently being used by 454 Life Sciences in their effort to deliver an affordable, fast and highly accurate full genome sequencing platform.[23]

 

Older techniques

Full genome sequencing of the entire human genome was first accomplished in 2000 partly through the use of shotgun sequencing technology. While full genome shotgun sequencing for small (4000–7000 base pair) genomes was already in use in 1979,[24] 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 locus,[25] 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.[26] In 1995 Roach et al.introduced the innovation of using fragments of varying sizes,[27] 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 (TIGR) to sequence the entire genome of the bacterium Haemophilus influenzae in 1995,[28] and then by Celera Genomics to sequence the entire fruit fly genome in 2000,[29] and subsequently the entire human genome. Applied Biosystems, now called Life Technologies, manufactured the shotgun sequencers utilized by both Celera Genomics and The Human Genome Project.

While shotgun sequencing was one of the first approaches utilized to successfully sequence the full genome of a human, it is too expensive and requires too long of a turn-around-time to be utilized for commercial purposes. Because of this, shotgun sequencing technology, even though it is still relatively 'new', is being displaced by technologies like pyrosequencing, SMRT sequencing, and nanopore technology.[30]

 

 

Race to commercialization

In October 2006, the X Prize Foundation, working in collaboration with the J. Craig Venter Science Foundation, established the Archon X Prize for Genomics,[31] 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 $10,000 per genome."[32] However, higher accuracy rates (or confirmatory methods) are desirable for some clinical applications. 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, which is a significant number of false positives and negatives. For the latter it is not known where the errors occur . The error rates required for widespread clinical use, such as Predictive Medicine[33] is currently set by over 1400 clinical single gene sequencing tests [34] (for example, errors in BRCA1 gene for breast cancer risk analysis). As of June 2009, the Archon X Prize for Genomics remains unclaimed.

In 2007, Applied Biosystems started selling a new type of sequencer called SOLiD System, with the first sale to Helicos Biosciences in 2008.[35] Helicos stated that, utilizing the new sequencers, they will attempt to provide a full genome sequencing service with a target price of $72,000 per sample.[36] However, this price point is still too high some applications, and is only competitive to DNA arrays (at $500 per sample) in cases where more than 0.1% of the genome is desired.

In 2008 and 2009, both public and private companies have emerged that are now in a competitive race to be the first mover to provide a full genome sequencing platform that is commercially robust for both research and clinical use,[37] including Illumina,[38] Sequenom,[39] 454 Life Sciences,[40] Pacific Biosciences,[41] Complete Genomics,[42] Intelligent Bio-Systems,[43] Genome Corp.,[44] and Helicos BioScience[45]. These companies are heavily financed and backed by venture capitalists, hedge funds, investment banks and, in the case of Illumina, Sequenom and 454, heavy re-investment of revenue into research and development, mergers and acquisitions, and licensing initiatives.[46][47][48]

In the race to commercialize full genome sequencing, companies have made claims about being able to offer a service at a specific time for a specific price that have turned out to not be true. Intelligent Bio-Systems stated in November 2007 that by the end of 2008 they would release a platform capable of a providing a $5,000 full genome sequence, but, as of March 2009, no such platform has yet to be released.[49]

Pacific Biosciences stated that they will start selling their full genome sequencers in early 2010. While they didn't disclose the cost to sequence a single genome, they did state they may not release their second-generation machine capable of a $1,000 genome until 2013.[36] Complete Genomics, however, stated that they'll be able to provide a $5,000 full genome sequencing service by the summer of 2009.[50] The accuracy, precision, and reproducibility of both Pacific Biosciences and Complete Genomics technology, however, is still unknown.

A personal genomics company located in Massachusetts, Knome.com, currently provides genome sequencing services but the cost is about $99,500 per genome (down from $350,000 per genome initially),[51] the turn-around time is unknown, the accuracy is unknown, and the number of people was limited to 20 for the first year, and is still considered early stage commercialization of full genome sequencing, focusing on wealthy customers.[52]

As of January 2009, there are no indications that any of these companies have been hindered by the global recession. And thus, the race appears to be proceeding forward at full speed. [53]

At the end of 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 99.99%, meaning that there is an error in one out of every ten thousand base pairs. 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 90x depth of coverage (each base in the genome was sequenced 90 times) while their commercialized sequence is reported to be only 40x, so the accuracy may be substantially lower unless they can find some way to improve it before their first service release planned for the summer 2009. This accuracy rate may be acceptable for research purposes, and clinical use would require confirmation by other methods of any reportable alleles.[54][55] In March 2009, it was announced that Complete Genomics has signed a deal with the Broad Institute to sequence cancer patient's genomes and will be sequencing five full genomes to start.[56] In April 2009, Complete Genomics announced that it plans to sequence 1,000 full genome's 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.[57] Complete Genomics plans to officially launch in June 2009, although it is unknown if their lab will have received CLIA-certification by that time.

In June 2009, Illumina announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30X for $48,000 per genome.[58] 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.[59][60] Jay Flatley, Illumina's President & CEO, stated that "during the next five years, perhaps markedly sooner," the price point for full genome sequencing will fall from $48,000 to under $1,000.[61] Illumina has already signed agreements to supply full genome sequencing services to multiple direct-to-consumer personal genomics companies.

 

Disruptive technology

Full genome sequencing provides information on a genome that is orders of magnitude larger than that provided by the current leader in sequencing technology, DNA arrays. For humans, DNA arrays currently provides genotypic information on up to one million genetic variants,[62][63][64] 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 to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500 per 1 million basepairs).[40] Agilent, another established DNA array manufacturer, is working on targeted (selective region) genome sequencing technologies[65]. It is thought that Affymetrix, 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.[66][67][68] 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. 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.[69]

 

Societal impact

Inexpensive, time-efficient full genome sequencing will be a major accomplishment not only for the field of Genomics, but for the entire human civilization 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. 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 and Personalized Medicine 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. However, it should be recognized that despite advancements in genome sequencing technology, incomplete understanding of the significance of individual variants or combinations of variants will limit the widespread usefulness of full genome sequencing in medicine until its clinical utility can be demonstrated.

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."[70] However, this potential use of genome sequencing runs counter to established norms for genetic testing of asymptomatic minors that have been well established in the field of genetic counseling.[71][72][73][74]

 

See also

  • DNA microarray
  • DNA profiling
  • Medical genetics
  • Human Genome Project
  • Personal Genome Project
  • List of sequenced eukaryotic genomes
  • List of sequenced bacterial genomes
  • List of sequenced archaeal genomes

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