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The History and Techniques of DNA Sequencing

written by: GiangNguyen • edited by: Anurag Ghosh • updated: 6/16/2009

One of the key requirements for developing personalized medicine is a fast and accurate DNA sequencing technology. Learn about the history of DNA sequencing here.

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    What is DNA sequencing?

    DNA sequencing is the process of determining the order of nucleotides in DNA. DNA sequencing is often talked about in the context of the Human Genome Project, in which, the human genome was successfully sequenced in 2001, providing scientists an incredible amount of data. The technology of DNA sequencing has evolved rapidly in the past 15 years. You now can pay companies to obtain your personal genome sequencing. This allows you to access your disease risk and to analyze and compare your genetic traits.

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    How does DNA sequencing work?

    DNA molecules consist of repeating nucleotides, which are the the bases of DNA. Nucleotides consist of adenine (A), thymine (T), guanine (G), and cytosine (C). DNA molecules are double-stranded, with two complimentary DNA strands forming a double helix. DNA sequencing aims to determine the exact order of the bases, A, T, C and G in a DNA fragment.

    The basic principle of DNA sequencing is simple and consists of two main steps. In the first step, labeled nucleotides are inserted into copies of a DNA fragment. In the second step, the DNA sequence is derived from the locations of the labeled nucleotides. The first step involves a technique called DNA amplification. First, the original double-stranded DNA is heated and separated into two single DNA strands. Then, these single strands are used as a template for making complementary copies. We then end up with a large number of fragments of different lengths. The second step involves separating the DNA fragments according to their lengths. This is often done by electrophoresis in a polyacrylamide gel. The base at the end of each fragment is identified, allowing reconstruction of the DNA sequence.

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    History of DNA Sequencing

    Prior to 1970s, no progress had been made toward the sequencing of DNA. In the mid 1970s, the technology of DNA sequencing was revolutionized by Sanger, who later on won his second Nobel Prize in chemistry for this invention. The complete DNA sequence of a viral genome was reported by Sanger in 1977. However, Sanger's technique of DNA sequencing was still very slow.

    By the begining of 1990s, only a handful of groups were able sequence DNA up to 100,000 bases at extremely high costs. The start of the Human Genome Project had inspired scientists and engineers to come up with automation techniques that not only speed up the process of DNA squencing but also to substantially lower its cost. DNA sequencing is now done routinely all round the world. There are now many laboratories that can sequence 100 million bases or more every year. In addition to the human genome, DNA sequencing is also used to obtain genomes of many organisms, including mice, rats, fruit flies, worms, yeast, fungi, microbes, plants, mosquitos, bacteria and viruses.



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