Medicine is transforming rapidly. During this era of human history, scientists are forever changing lives, because for the first time humans are not powerless against their genes! We now have the power to not only predict, but also alter our very future. The Genetic Revolution is here!
With the power of gene therapy, scientists now have a new tool that enables them to change a patient's DNA. Medical treatments usually counteract the symptoms of a disease. But with gene therapy, doctors can cure diseases. Click to learn more
The concepts described in this website might be a review for some people, or it might be a new learning experience. Click in order to learn or review the basics of biology and genetics.
Medicine is transforming rapidly. During this era of human history, scientists are forever changing lives, because for the first time humans are not powerless against their genes! We now have the power to not only predict, but also alter our very future. The Genetic Revolution is here!
Innovators
The following is a list of innovators that are helping in the development and commercialization of genomics, DNA sequencing, and other DNA technologies.
Major Organizations
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The National Human Genome Research Institute was established in 1989. It, along with 26 other institutes and centers, makes up the National Institutes of Health (NIH). It is a massive research center which studies cancer, genetics and molecular biology, inherited diseases, medical genetics, the identification of genes responsible for diseases, development of DNA microarray technologies, designs of new approaches for diagnosing and treating genetic diseases, and much more.
The GenBank is the genetic sequence database of the National Institute of Health (NIH). It provides public sequences of DNA for scientific studies. It is part of the International Nucleotide Sequence Database Collaboration, and shares data daily with other organizations. GenBank allows scientists to collaborate and research on the same technology. Because every scientist can have access to the millions of DNA sequences and information contained within GenBank, it is one of the most important innovation to date in genomics.
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The International Cancer Genome Consortium (ICGC) focuses on coordinating multiple research projects all over the world. All of these projects have a single aim: studying genomic changes which can cause cancer. Studying about 50 different types of cancer, the ICGC hopes to generate detailed catalogs of genomic abnormalities from these tumor types. After the data are accumulated, the ICGC will make it available with little restriction to the entire research community to increase collaboration and accelerate cancer treatment and research.
University Based Innovators
Comprised of 15 state of the art experimental and computational faculties, the UC Davis Genome Center utilizes experimental and computational approaches to figure out key problems in genomics. It focuses highly on DNA sequencing, genotyping, and expression analysis. It is developing and using new technologies such as chromatin immunoprecipitation, DNA sequencing libraries, and high-throughput sequencing platforms.
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Yale University Center for Genomics and Proteomics teaches and researches numerous topics relating to Genomics and Proteomics, such as small molecule screening, chemical genomics, comparative genomics, ribonomics and bioinformatics. It strives to understand more deeply the nature of gene regulation, protein and gene functions, genetic diseases, and more by using model organisms like microbes, plants, and humans.
Duke Institute for Genome Sciences and Policy (IGSP) is dedicated to studying and researching genome sciences and policy. Founded in 2003, IGSP is a response to the great development that had emerged in genomic sciences. In addition to researching and studying genomics, this institute also hopes to understand the full impact of genomics on society, life, and policy.
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The Stanford Center for Genomics and Personalized Medicine hopes to advance genomic technology to the point where it will someday be a powerful and normal tool for predicting diseases. In addition to scientific research, SCGPM also promotes genomic research, educates physicians, and analyzes the ethics of personalized medicine. Established in 2009, The SCGPM is now involved in more than 60 faculties from 13 departments.
The Genome Institute (TGI) at Washington University is uniquely pushing the limits of academic research by implementing new approaches to the study of biology, evolution, human health, and disease. Its mission is to improve human condition through collecting and studying genomic data, and sharing the data in order to encourage collaborations. One of the three NIH funded sequencing centers, TGI contributed 25% of the finished sequence in the Human Genome Project.
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Next Generation Sequencing Innovators
In the late 1900s, the idea of using nanopores as a biosensor was first proposed. Founded in 2005, Oxford Nanopores worked to translate nanopore science into an electronics-based technology. Nanopores are nano-scale holes, which may be biological or solid-state. Biological nanopores are formed by pore-forming proteins in a membrane. The membranes are usually lipid bilayers. Solid-state nanopores are created by silicon nitride, graphene, or other synthetic materials. If a molecule passes through the pore or near it, a characteristic disruption of the current is made. Each molecule will make a different current change, thus making it possible to differentiate between the four standard DNA bases and other modified bases.
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(193) Distinction between the four bases can be made base on the characteristics of the disrupted current
Now part of QIAGEN, Pyrosequencing Technology sequence DNA through synthesis, a technique which can be used for accurate and quantitative analysis. First a "primer" is hybridized to a single-stranded PCR amplicon. This is used as a template which is incubated with specific enzymes and substrates. Deoxribonucleotide triphosphate (dNTP) is added to the reaction.
DNA polymerase then catalyzes and incorporates the dNTP into the DNA strand, only if it is complementary to the base in the template strand. Each incorporation results in the release of pyrohosphate (PPi).
PPi is converted to ATP when ATP sulfurylase is in the presence of adenosine 5' phosphosulfate (APS). The ATP drives the conversion of luciferin to oxyluciferin, which generates visible light. The light is in proportion to the amount of ATP. This light is detected by a CCD chip and is seen as a peak in the raw data output. The height of each peak is proportional to the number of nucleotides which were incorporated.
A nucleotide-degrading enzyme called Apyrase continuously degrades nucleotides and ATP which were not incorporated. Another nucleotide is added after the degradation is completed.
dNTPs is continuously added during the process. The signal peaks in the Pyrogram trace are used to built the DNA strand and determine the nucleotide sequence.
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Video on Pyrosequencing
First debuted in 2006, the Illumina method has been used to sequence genomes for African, Asian and cancer patients. A strong fluorescent signal is made by bounding fragments to a slide and growing them in clusters.
A single stranded DNA sample is first broken into smaller pieces. Short DNA sequences called adaptors are attached to the DNA fragments.
The fragments are placed onto a slide with a covering of primers attached. In a process called amplification, the DNA bends over and search for a complementary primer on the surface. A complementary strand of DNA is then made from the primer on the surface. The replication process is repeated after the strands are split apart.
This creates a dense cluster of DNA on each channel of the slide. A type of strand is then discarded, after which primers, polymerase, and nucleotides are added to the mix. As the bases are getting incorporated a laser is utilized to activate the fluorescence, allowing the colors to be read. A computer is used to monitor each clusters, analyzing each color as a new base is added. It then works out the sequence from the many clusters.
Illumina is a fast and cheap way to read short DNA fragments It can read one gigabase, which is about 1/3 of the human genome in just half a day, for just $0.001 per 1000 bases.
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(197) Illumina DNA Sequencer
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SOLiD sequencing, developed by Life Technologies, uses "color-space". These "color-space" binds fluorescent primers to the DNA, two nucleotides at a time. This "di-nucleotide" pair will have a color that will correlates with a double of any nucleotide. It is very important that the first nucleotide be known, otherwise a mistake will mean that the entire read is wrong.
Part of Life Technologies, Ion Torrent Systems Inc. uses Ion Semiconductor Sequencing in order to simply sequence DNA. Usually in nature, when a strand of DNA incorporates a nucleotide (using a polymerase), a hydrogen ion is released as a byproduct. Ion Torrent Systems Inc. uses a high-density array of micro-machined wells, which perform this biochemical process in each well. Each well has a different DNA template with an ion-sensitive layer under the well. Beneath the ion-sensitive layer is a proprietary Ion sensor.
When a base is incorporated into a DNA template, a hydrogen ion is released. The charge of the ion will change the pH of the solution, which is detected by the ion sensor. This sensor is one of the world's smallest slid-state pH meter. It will then call and recognizes the base.
Because the sensor directly translates chemical information to digital data without the use of light, cameras, or scanners; each nucleotide is recorded in seconds.
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(202) Raw Photo Recording of Nucleotides
tSMS, or True Single Molecule Sequencing simultaneously sequences large numbers of single DNA strands by using a form of sequencing-by-synthesis in which bases are labeled and added to the nucleic acid templates captured on a flow cell.
Billions of single molecules of sample DNA are captured within two flow cells. These captured strands are templates for the sequencing process. First polymerase and one fluorescently labeled nucleotide (C, G, A or T) are added. The polymerase incorporates the fluorescent nucleotides into newly formed complementary strands on all the templates. After a "wash step", all the free nucleotides are removed.The incorporated nucleotides are imaged and their positions are recorded.
The fluorescent group is efficiently removed, leaving behind incorporated nucleotides. The process will continue through each three bases.
This results in complementary stands greater than 25 bases in length created on billions of templates.
SMRT sequencing enables the observation of DNA synthesis while it is occurring in real time. This is possible through to three innovations: the SMRT Cell, Phospholinked nucleotides, and the PacBio RS.
The bases are labeled with different fluorescent dyes which each have a distinct emission spectrum. Nucleotides held by the polymerase and the enzyme responsible for replicating DNA emits an extended signal which is used to identify the base.
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