Frederick sanger dna sequencing

Frederick Sanger received two Nobel prizes (in the same category), for his work on protein sequencing and DNA sequencing.

Frederick Sanger (1918-2013)

Frederick Sanger was born in Rendcombe, England. His father was a medical doctor and it was expected that Fred would also enter the medical field. As Sanger grew up, he became very interested in nature and science and when he went to Cambridge University, he made the decision not to study medicine. He felt that a career in science would give him a better chance to become a problem solver.

Sanger was a conscientious objector during the war because of his Quaker upbringing. After his B.A. in 1939, he stayed at Cambridge to do a Ph.D. with Albert Neuberger, on amino acid metabolism. After his Ph.D. in 1943, Sanger started working for A. C. Chibnall, on identifying the free amino groups in insulin. In the course of identifying the amino groups, Sanger figured out ways to order the amino acids. He was the first person to obtain a protein sequence. By doing so, Sanger proved that proteins were ordered molecules and by analogy, the genes and DNA that make these proteins should have an order or sequence as well. Sanger won his first Nobel Prize for Chemistry in 1958 for his work on the structure of protein.

By 1951, Sanger was on the staff of the Medical Research Council at Cambridge University. In 1962, he moved with the Medical Research Council to the Laboratory of Molecular Biology in Cambridge where Francis Crick, John Kendrew, Aaron Klug and others were all working on a DNA-related problem. Solving the problem of DNA sequencing became a natural extension of his work in protein sequencing. Sanger initially investigated ways to sequence RNA because it was smaller. Eventually, this led to techniques that were applicable to DNA and finally to the dideoxy method most commonly used in sequencing reactions today. Sanger won a second Nobel Prize for Chemis

Method of DNA sequencing developed in 1977

Sanger sequencing is a method of DNA sequencing that involves electrophoresis and is based on the random incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitroDNA replication. After first being developed by Frederick Sanger and colleagues in 1977, it became the most widely used sequencing method for approximately 40 years. An automated instrument using slab gel electrophoresis and fluorescent labels was first commercialized by Applied Biosystems in March 1987. Later, automated slab gels were replaced with automated capillary array electrophoresis. More recently, higher volume Sanger sequencing has been replaced by next generation sequencing methods, especially for large-scale, automated genome analyses. However, the Sanger method remains in wide use for smaller-scale projects and for validation of deep sequencing results. It still has the advantage over short-read sequencing technologies (like Illumina) in that it can produce DNA sequence reads of > 500 nucleotides and maintains a very low error rate with accuracies around 99.99%. Sanger sequencing is still actively being used in efforts for public health initiatives such as sequencing the spike protein from SARS-CoV-2 as well as for the surveillance of norovirus outbreaks through the Center for Disease Control and Prevention's (CDC) CaliciNet surveillance network.

Method

The classical chain-termination method requires a single-stranded DNA template, a DNA primer, a DNA polymerase, normal deoxynucleotide triphosphates (dNTPs), and modified di-deoxynucleotide triphosphates (ddNTPs), the latter of which terminate DNA strand elongation. These chain-terminating nucleotides lack a 3'-OH group required for the formation of a phosphodiester bond between two nucleotides, causing DNA polymerase to cease extension of DNA when a modified ddNTP is inco

"A journey of exploration through unknown territory without a clear objective" † Collated and written by Dr Lara Marks

DNA sequencing is one of the most important tools in medicine today. Used to determine the precise order of the four building blocks that make up a piece of DNA, the method is most well known for its role in mapping out the first human genome, completed in 2003. Beyond sequencing the human genome, DNA sequencing lies at the heart of many other medical applications, ranging from the diagnosis of diseases like cancer to monitoring the mutation of bacteria and their resistance to drugs like antibiotics. It is also critical in tailoring medical treatment according to each person's genetic profile, known as personalised medicine.

Yet, despite its importance, relatively few people outside the scientific community know how DNA sequencing came into the world or how it came to be adopted for medical purposes. The development of DNA sequencing began in the 1940s when a British biochemist, Fred Sanger, took up the quest started by scientists in the late nineteenth century to work out the composition of proteins, molecules fundamental to every biological process in the body. Sanger was to become one of a small handful of scientists ever to be awarded a Nobel Prize twice (the others being Marie Curie, John Bardeen and Linus Pauling). The first, in 1958, was for determining the structure of insulin, which demonstrated for the first time that proteins were real chemicals with a defined sequence; the second, in 1980, was for his pioneering sequencing method for DNA, which laid the basis for the genomic revolution.

Despite his achievements, Sanger's life has received relatively little popular attention and his achievements have largely been overshadowed by that of James Watson and Francis Crick's work on the double-helix of DNA, which has attracted much public interest. In part this can be attributed to Sanger's quiet and mod