DNA Sequencing

Definition

DNA sequencing is a method used to determine the precise order of the four nucleotide bases – adenine, guanine, cytosine and thymine - that make up a strand of DNA. These bases provide the underlying genetic basis (the genotype) for telling a cell what to do, where to go and what kind of cell to become (the phenotype). Nucleotides are not the only determinants of phenotypes, but are essential to their formation. Each individual and organism has a specific nucleotide base sequence.

The two scientists in the photograph are reading the genetic code for a DNA sample on a highlighted light board. Such analysis is usually done by a computer. Credit: National Cancer Institute.

Importance

DNA sequencing played a pivotal role in mapping out the human genome, completed in 2003, and is an essential tool for many basic and applied research applications today. It has for example provided an important tool for determining the thousands of nucleotide variations associated with specific genetic diseases, like Huntington's, which may help to better understand these diseases and advance treatment.

DNA sequencing also underpins pharmacogenomics. This is a relatively new field which is leading the way to more personalised medicine. Pharmacogenomics looks at how a person's individual genome variations affect their response to a drug. Such data is being used to determine which drug gives the best outcome in particular patients. Over 140 drugs approved by the FDA now include pharmacogenomic information in their labelling. Such labelling is not only important in terms of matching patients to their most appropriate drug, but also for working out what their drug dose should be and their level of risk in terms of adverse events. Individual genetic profiling is already being used routinely to prescribe therapies for patients with HIV, breast cancer, lymphoblastic leukaemia and colon cancer and in the future will be used to tailor treatments for cardiovascular disease, cancer, asthma, Alzheimer's disease and depression. Drug developers are also using pharmacogenomic data to design drugs which can be targeted at subgroups of patients with specific genetic profiles.

Discovery

Although scientists established DNA had a double helix structure in 1953, it was to be many more years before they could analyse DNA fragments. In part this reflected the fact that small DNA molecules contain several thousands of nucleotides and it was difficult to obtain large quantities of homogeneous DNA. Scientists also lacked the means to degrade DNA which they needed for sequence analysis.

A new chapter opened up in the 1960s with the emergence of techniques to sequence ribonucleic acid (RNA)s. Ray Wu, a Chinese American biologist based at Cornell University, published one of the first methods for sequencing DNA in 1970. Using highly labelled deoxynucleotides (single units of DNA) and DNA polymerase he found a way to sequence the terminal region of a DNA molecule. Critically, Wu's approach broke the DNA sequence down into several different components for analysis, thereby circumventing the need for large quantities of homogeneous DNA. Subsequently, in 1971, Wu demonstrated his method could sequence the ends of DNA in lambda phage, and two years later that it had the capacity to determine the sequence of any DNA.

Over the course of the 1970s Wu's method was modified by Fred Sanger at the Laboratory of Molecular Biology in Cambridge, UK. In 1975 Sanger, together with Alan Coulson, published what became known as the 'Plus and Minus' technique. This enabled the sequencing of up to 80 nucleotides in one go. Three years later, in 1977, Sanger and his colleagues announced another technique called the 'Sanger method' or 'dideoxy sequencing'. This made it possible to sequence much longer stretches of DNA very rapidly. Their approach appeared alongside the reporting of another technique by Allan Maxam and Walter Gilbert at Harvard University.

While the Maxam-Gilbert method initially proved the most popular, it soon fell out of favour because it necessitated the use of hazardous chemicals and radioisotopes. Added to this, the method it was difficult to scale-up and could not be used in standard molecular biology kits because of its technical complexity. By contrast, the Sanger method gained popularity because it was easier to use and more reliable. It was also amenable to automation, paving the way to the first generation of automated DNA sequencers. The first automated DNA sequencer was devised in 1986 by Leroy Hood and colleagues at the California Institute of Technology together with a team including Lloyd Smith and Michael and Tim Hunkapiller. These machines used capillary electrophoresis rather than gel electrophoresis using slabs.

Several new DNA sequencing methods and machines have been developed since the 1990s. These were built following the introduction of microfluidic separation devices which improved sample injection and speeded up separation times. Such innovations improved both the efficiency and accuracy of sequencing, allowing for high-throughput sequencing, and radically lowered the cost. Between 2001 and 2011 the cost of sequencing a genome shrank from $100 million to $10,000.

Application

DNA sequencing provides the means to know how nucleotide bases are arranged in a piece of DNA. Several methods have been developed for this process. These have four key steps. In the first instance DNA is removed from the cell. This can be done either mechanically or chemically. The second phase involves breaking up the DNA and inserting its pieces into vectors, cells that indefinitely self-replicate, for cloning. In the third phase the DNA clones are placed with a dye-labelled primer (a short stretch of DNA that promotes replication) into a thermal cycler, a machine which automatically raises and lowers the temperature to catalyse replication. The final phase consists of electrophoresis, whereby the DNA segments are placed in a gel and subjected to an electrical current which moves them. Originally the gel was placed on a slab, but today it is inserted into a very thin glass tube known as a capillary. When subjected to an electrical current the smaller nucleotides in the DNA move faster than the larger ones. Electrophoresis thus helps sort out the DNA fragments by their size. The different nucleotide bases in the DNA fragments are identified by their dyes which are activated when they pass through a laser beam. All the information is fed into a computer and the DNA sequence displayed on a screen for analysis.

The method developed by Sanger was pivotal to the international Human Genome Project. Costing over US$3 billion and taking 13 years to complete, this project provided the first complete Human DNA sequence in 2003. Data from the project provided the first means to map out the genetic mutations that underlie specific genetic diseases. It also opened up a path to more personalised medicine, enabling scientists to examine the extent to which a patient's response to a drug is determined by their genetic profile. The genetic profile of a patient's tumour, for example, can now be used to work out what is the most effective treatment for an individual. It is also hoped that in the future that knowing the sequence of a person’s genome will help work out a person's predisposition to certain diseases, such as heart disease, cancer and type II diabetes, which could pave the way to better preventative care.

Data from the the Human Genome Project has also helped fuel the development of gene therapy, a type of treatment designed to replace defective genes in certain genetic disorders. In addition, it has provided a means to design drugs that can target specific genes that cause disease.

Beyond medicine, DNA sequencing is now used for genetic testing for paternity and other family relationships. It also helps identify crime suspects and victims involved in catastrophes. The technique is also vital to detecting bacteria and other organisms that may pollute air, water, soil and food. In addition the method is important to the study of the evolution of different population groups and their migratory patterns as well as determining pedigree for seed or livestock.

DNA Sequencing: timeline of key events

The first to determine the DNA sequence of insulin, Sanger proved proteins have a defined chemical composition. He was also pivotal to the development of the dideoxy chain-termination method for sequencing DNA molecules, known as the Sanger method. This provided a breakthrough in the sequencing of long stretches of DNA in terms of speed and accuracy and laid the foundation for the Human Genome Project. 1918-08-13T00:00:00+0000Ray Wu pioneered the first primer-extension method for DNA sequencing which laid the foundation for the Human Genome Project. He was also instrumental in the application of genetic engineering to agricultural plants to improve their output and resistance to pests, salt and drought. 1928-08-14T00:00:00+0000Werner Arber is a geneticist and microbiologist. He shared the 1978 Nobel Prize in 1978 for helping to discover restriction enzymes and showing their application in molecular genetics. It was based on some work he carried out in the 1960s. Arber indicated in 1965 that restriction enzymes could be used as a tool for cleaving DNA. The enzymes are now an important tool for genetic engineering. 1929-06-03T00:00:00+0000Griffin was a leading expert on viruses that cause cancer. She was the first woman appointed to Royal Postgraduate Medical School, Hammersmith Hospital. In 1980 she completed the sequence of the poliovirus, the longest piece of eukaryotic DNA to be sequenced at that time. She devoted her life to understanding the Epstein-Barr virus, the cause of Burkitt's Lymphoma, a deadly form of cancer. The virus is also now thought to cause multiple sclerosis. 1930-01-23T00:00:00+0000Hamilton O Smith is an American microbiologist who helped isolate and characterised the first restriction enzyme from the bacteria Haemophilus influenzae. This he achieved with Kent Wilcox in 1970. They showed that the enzyme degrades foreign phage DNA but not the host's DNA. Now known as HindIII, the restriction enzyme went on to become a major tool for cutting and pasting of specific DNA fragments for the generation of recombinant DNA. Smith was awarded the Nobel Prize for Physiology or Medicine in 1978 for his part in the discovery of the enzyme. In 1995 he and a team at the Institute for Genomic Research completed the DNA sequence of Haemophilus influenzae. It was the first bacterial genome to be deciphered. Later on he helped in the genomic sequencing efforts for the fruit fly and humans at Celera Genomics. 1931-08-23T00:00:00+00001932-01-01T00:00:00+0000Gilbert is a molecular biologist. He was involved in some of the early efforts to pioneer techniques for determining base sequences in nucleic acids, known known as DNA sequencing, for which he shared the Nobel Prize for Chemistry in 1980. He was the first scientist to propose the existence of intron and exons. In 1986 Gilbert became a proponent of the theory that the first forms of life evolved out of replicating RNA molecules. The same year he began campaigning to set up the Human Genome Project. He was also a co-founder and the first Chief Executive Officer of Biogen, a biotechnology company originally set up to commercialise genetic engineering.1932-03-21T00:00:00+0000Studies a combination of chemistry, physics, maths and physiology and specialises in biochemistry in his final year.1936-01-01T00:00:00+0000Initially supervised by Bill Pirie, and then by Albert Neuberger, in the Department of Biochemistry. Thesis: 'On the metabolism of the amino acid lysine in the animal body'. 1940-01-01T00:00:00+0000Sulston was a biologist who played a central role in sequencing the genome of the Caenorhabditis elegans, a transparent nematode (roundworm). It was the first animal to have its genome sequenced. Based on his work with the nematode, Sulston helped set up the project to sequence the human genome which he did as director of the Sanger Centre. The first draft of the human genome sequence was completed in 2000. In 2002 he shared the Nobel Prize for identifying how genes regulate the life cycle of cells through apoptosis. 1942-03-27T00:00:00+0000Sanger undertakes the research as part of team working with Albert Chibnall in Department of Biochemistry. His work is initially supported by a Beit Memorial Fellowship from 1944 and then by Medical Research Council from 1951. 1944-01-01T00:00:00+0000Venter is a biochemist and geneticist who was involved in the setting up of Celera Genomics, The Institute for Genomic Research and J Craig Institute which helped sequence the first human genome. In 2010 Venter worked with a team to create the first form of synthetic life. This involved synthesising a long molecule of DNA that contained an entire bacerum genome and then inserting this into another cell. 1946-10-14T00:00:00+0000Noted by Salvador Luria and his graduate student Mary Human while conducting experiments into the break-up of DNA in phage-infected bateria.1952-01-01T00:00:00+0000Sanger's insulin results establish for the first time that proteins are chemical entities with a defined sequence. The technique Sanger develops for sequencing insulin later becomes known as the degradation or DNP method. It provides the basis for his later development of sequencing tecdhniques for nucleic acids, including RNA and DNA.1955-01-01T00:00:00+0000Ingram shows that the difference between sickle-cell and normal haemoglobulin lies in just one amino acid. 1957-01-01T00:00:00+0000Prize awarded to Sanger 'for his work on the structure of proteins, especially that of insulin'.1958-01-01T00:00:00+0000Non-profit institution founded by Robert S Ledley to explore the use of computers in biomedical research. It is eventually located at Georgetown University Medical Center in Washington, D.C.1960-01-01T00:00:00+00001960-01-01T00:00:00+0000Sanger now has close contact with protein crystallographers, molecular geneticists and protein chemists1962-01-01T00:00:00+0000Werner Arber, Swiss microbiologist and geneticist, and his doctoral student Daisy Dussoix proposed that bacteria produce restriction and modification enzymes to counter invading viruses. They published their findings in 'Host specificity of DNA produced by Escherichia coli I and II', Journal Molecular Biology, 5 (1962), 18–36 and 37-49.1962-01-23T00:00:00+0000Robert Holley and colleagues sequence Escherichia coli alanine transfer RNA, laying the foundation for DNA sequencing. 1965-01-01T00:00:00+0000The book contained all protein sequences known to-date. It was the result of a collective effort led by Margaret Dayhoff to co-ordinate the ever-growing amount of information about protein sequences and their biochemical function. It provided the model for GenBank and many other molecular databases. 1965-01-01T00:00:00+0000900 page monograph provides the first introduction to the application of digital computing in biology and medicine. 1965-01-01T00:00:00+0000Tested on ribosomal RNA1965-01-01T00:00:00+0000The prediction was published in W. Arber, 'Host-controlled modification of bacteriophage', Annual Review Microbiology, 19 (1965), 365-78. it was based on some research he carried out in the early 1960s with his doctoral student, Daisy Dussoix. They found that bacteria protect themselves against invading viruses by producing two types of enzymes. One cut up the DNA of the virus and the other restricted its growth. Arber believed these two enzymes could provide an important tool for cutting and pasting DNA, the method now used in genetic engineering. 1965-10-01T00:00:00+0000The sequencer was developed by Pehr Victor Edman with Geoffrey Begg1967-01-01T00:00:00+0000Ray Wu and A.D. Kaiser report on the partial sequence of bacteriophage lambda DNA in the Journal of Molecular Biology, 35/3 (1968), 523-37. 1968-01-01T00:00:00+0000Kjell Kleppe, a Norwegian scientist working in H. Gobind Khorana's Institute for Enzyme Research at University of Wisconsin publishes papers describing the principles of PCR.1969-01-01T00:00:00+0000Called Thermus aquaticus (Taq) this enzyme becomes a standard source of enzymes because it can withstand higher temperatures than those from E Coli. Taq is later important in the PCR technique. 1969-01-01T00:00:00+0000The finding was published in Hamilton O Smith, Kent W Wilcox, 'A restriction enzyme from Hemophilus influenzae. I. Purification and general properties',Journal of Molecular Biology, 51/2 (1970), 379-91. Restriction enzymes are now workhorses of molecular biology. They are essential in the development of recombinant DNA and were pivotal to the foundation of the biotechnology industry. 1970-07-01T00:00:00+0000K. Kleppe, E Ohtsuka, R Kleppe, I Molineux, HG Khorana, "Studies on polynucleotides *1, *2XCVI. Repair replication of short synthetic DNA's as catalyzed by DNA polymerases", Journal of Molecular Biology, 56/2 (1971), 341-61. The method provides an artificial system of primers and templates that allows DNA polymerase to copy segments of the gene being synthesised. 1971-01-01T00:00:00+0000The 12 base sequence of bacteriophage lambda DNA is published by Ray Wu and Ellen Taylor in the Journal of Molecular Biology, 57 (1971) 0, 491-511. 1971-05-01T00:00:00+0000The power of restriction enzymes to cut DNA was demonstrated by Kathleen Danna, a graduate student, with Daniel Nathans, her doctoral supervisor, at Johns Hopkins University. They published the technique in 'Specific cleavage of simian virus 40 DNA by restriction endonuclease of Hemophilus influenzae', PNAS USA, 68/12 (1971), 2913-17.1971-12-01T00:00:00+0000This is achieved by Walter Gilbert and Allan Maxam at Harvard University using a method known as wandering-spot analysis.1973-01-01T00:00:00+0000The method enables 80 nucleotides to be sequenced in one go. Represents radical new approach which allows direct visual scanning of a sequence. 1975-01-01T00:00:00+0000This is found to contain 5,385 nucleotides. It is the first DNA based organism to have its complete genome sequenced. Sanger and his team use the plus and minus technique to determine the sequence. 1977-01-01T00:00:00+0000Duncan McCallum, a business computer programmer in Cambridge wrote the first computer programme for DNA sequencing. It was used by Sanger's sequencing group at the MRC Laboratory of Molecular Biology. 1977-01-01T00:00:00+0000Two separate teams, one led by Fred Sanger at the MRC Laboratory of Molecular Biology, Cambridge, UK, and one composed of Allan Maxam, and Walter Gilbert at Harvard University publish two different methods for sequencing DNA. The first, known as the Sanger Method, or dideoxy sequencing, involves the breaking down and then building up of DNA sequences. The second, the Maxam-Gilbert method, involves the partial chemical modification of nucleotides in DNA. 1977-02-01T00:00:00+0000The prize was jointly awarded to Werner Arber, Daniel Nathans and Hamilton O Smith. Arber was the first to discover the enzymes; Smitth demonstrated their capacity to cut DNA at specific sites and Nathans showed how they could be used to construct genetic maps. With their ability to cut DNA into defined fragments restriction enzymes paved the way to the development of genetic engineering. 1978-10-01T00:00:00+0000Prize shared with Walter Gilbert. Awarded on the basis of their 'contributions concerning the determination of base sequences in nucleic acids.' 1980-01-01T00:00:00+0000The aim is to establish a centralised sequence computerised database tha is available free of charge. 1980-01-01T00:00:00+0000Conducted by a team led by Beverly Griffin, the project's completion was a major achievement. It was one of the largest tracts of eukaryotic DNA sequenced up to this time. The work was published in E Soeda, JR Arrand, N Smolar, JE Walsh, BE Griffin, ‘Coding potential and regulatory signals of the polyoma virus genome’, Nature, 283 (1980) 445-53.1980-01-01T00:00:00+0000The database was started by Margaret Dayhoff at the NBRF in the mid 1960s and comprised over 200,000 residues. Within a month of its operation more than 100 scientists had requested access to the database. The database was funded with contributions from m Genex, Merck, Eli Lilly, DuPont, Hoffman–La Roche, and Upjohn, and computer time donated by Pfizer Medical Systems.1980-09-15T00:00:00+0000In this method genomic DNA is randomly fragmented and cloned to produce a random library in E Coli. The clones are then sequenced at random and the results assembled by computer which compares all of the sequence reads and aligns the matching sequences to produce the complete genome sequence. 1982-01-01T00:00:00+0000Funding secured for the setting up of GenBank, to be located at Los Alamos National Laboratory. It was to serve as a repository for newly determined sequences, as a tool for sequencers assembling genomes and for bioinformatic researchers. 1982-06-01T00:00:00+00001983-01-01T00:00:00+0000Kary Mullis, an American biochemist based at Cetus, proposed an alternative method to Sanger's DNA sequencing method to analyse Sickle cell Anaemia mutation which laid the foundation for the development of the PCR technique. 1983-05-01T00:00:00+0000Mullis reports on his production of olgionucleotides and some results from his experiments with PCR to Cetus Corporation's annual meeting but few show any interest. 1984-06-01T00:00:00+0000The first genetic fingerprint was discovered by accident by Alec Jeffrey when conducting experiments to look at how genetic variations evolved. 1984-09-10T00:00:00+0000The application establishes polymerase chain reaction (PCR) as a method for amplifying DNA in vitro. PCR uses heat and enzymes to make unlimited copies of genes and gene fragments. The application is broad and is based on analysis of Sickle Cell Anaemia mutation via PCR and Oligomer restriction. 1985-03-01T00:00:00+0000This was developed by the British geneticist Alec Jeffreys. He developed the technique as part of his efforts to trace genes through family lineages. It was based on his discovery that each individual had unique numbers of repeated DNA fragments, called restriction fragment length polymorphisms, in their cells. The principle was described in A J Jeffreys, V Wilson, S L Thein, 'Hypervariable 'minisatellite' regions in human DNA', Nature, 314 (1985), 67-73. 1985-03-07T00:00:00+0000Undertaken to prove maternity of a 15 year old boy threatened with deportation to Ghana by the UK Home Office because of doubts over the identity of his mother, an immigrant based in the UK. The test proved the boy was related to his mother. Without the test the mother and son would not have been able to remain together in the same country. 1985-05-17T00:00:00+0000The PCR technique enabled the amplification of small fragments of DNA on a large scale. It was published in RK Saiki et al, 'Enzymatic Amplification of beta-globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia', Science, 230 (1985), 1350-54.1985-12-20T00:00:00+0000Leroy Hood and colleagues at the California Institute of Technology together with a team including Lloyd Smith and Michael and Tim Hunkapiller, develop the first automated DNA sequencing machine. The machine is commercialised by Applied Biosystems. 1986-01-01T00:00:00+0000Biologists gathered at Cold Spring Harbor Laboratory laid out the first plans for mapping and sequencing the human genome. Among those attending were Walter Gilbert, James Watson and Paul Berg. Many scientists were highly sceptical that such a project was feasible because of the large size of the genome and the time and costs involved. Up to this point scientists had only managed to sequence some viral DNAs which had 100,000 DNA base pairs. The human genome was 10,000 bigger in size. 1986-04-30T00:00:00+0000Funding secured for precursor of the Human Genome Project. US$10.7 million provided by Department of Energery and US$17.2 million by National Institutes of Health.1988-01-01T00:00:00+0000This method, called FASTA, is published by William R Pearson and David J Lipman in Proc Natl Acad Sci USA, 85/8 (April 1988), 2444-8. This is now a common tool for bioinformatics. It allos for the comparison and aligning of sequences. 1988-04-01T00:00:00+00001989-05-25T00:00:00+0000Joint working group of the US Department of Energy and the National Institututes of Health present plan Understanding Our Genetic Inheritance: The US Human Genome Project.1990-02-01T00:00:00+0000An international scientific collaboration, the project was initiated by the US Department of Energy. Its aim was to determine the sequence of chemical base pairs which make up DNA, and to identify and map approximately 20,000 to 25,000 genes of the human genome. 1990-10-01T00:00:00+0000The was determined by a team led by Marie-Claire King who conducted a genetic analysis of 23 extended families, a total of 329 relatives. J Hall, M Lee, B Newman, J Morrow, L Anderson, B Huey, M King, 'Linkage of early-onset familial breast cancer to chromosome 17q21', Science, 250/4988 (1990): 1684–89. 1990-12-01T00:00:00+0000A team at the at the University of Washington, led by Mary-Claire King, demonstrated that a single gene on chromosome 17, later known as the BRCA1 gene, induced many breast and ovarian cancers. This was a major breakthrough as prior to this most scientists were sceptical of the role played between genetics and complex human disease. The team published their findings in JM Hall, et al, 'Linkage of early-onset familial breast cancer to chromosome 17q21', Science, 250/4988 (1990), 1684-89. 1990-12-21T00:00:00+00001992-01-01T00:00:00+0000H Bayley, MW Krishnasastry, BJ Walker, JJ Kasianowicz (1992) 'Assembly of a-hemolysin: A proteinaceous pore with potential applications in materials synthesis', MRS Symposium Proceedings, 292, 243-52.1992-01-01T00:00:00+0000M. Frommer, L.E. McDonald, D.S. Millar, C.M. Collis, F. Watt, G.W. Grigg, P.L. Molloy, C.L. Paul, 'A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands', PNAS, 89/5 (1992), 1827-31.1992-03-01T00:00:00+0000David Deamer tested out the pore with John Kasianowicz1992-12-01T00:00:00+0000The application (patent number 5,795,782 ) was a joint one from Harvard University and the University of California. It incorporated two different techniques proposed by David Deamer and Georges Church. 1995-03-17T00:00:00+0000A team of scientists led by Craig Venter at The Institute of Genomics Research published the first complete sequence of the 1.8 Mbp genome of Haemophilus influenzae, a type of bacteria that can cause ear and respiratory infections, as well as meningitis in children. R D Fleischmann, et al, 'Whole-Genome Random Sequencing and Assembly of Haemophilus influenzae Rd', Science, 269/5223 (1995), 496–512.1995-07-28T00:00:00+00001996-01-01T00:00:00+0000Mostafa Ronaghi and Pal Nyren at the Royal Institute of Technology in Stockholm develop pyrosequencing which allows for shotgun sequencing without cloning in E coli or any host cell. The marchinery and reagents involved in the method was first commercialised by Pyrosequencing AB.1996-01-01T00:00:00+0000JJ Kasianowicz, E Brandin, D, Branton, D Deamer (Nov 1996) 'Characterization of individual polynucleotide molecules using a membrane channel', Proceedings of National Academy of Science U.S., 93, 13770-73.1996-11-01T00:00:00+0000Celera Corporation launches a parallel effort to sequence the human genome to the Human Genome Project. Celera's entry into the field pose policy concerns about open access to gene sequencing data and accelerates the sequencing process in the Human Genome Project. 1998-05-01T00:00:00+0000The genome sequence of Mycobacterium tuberculosis consists of approximately 4,400,000-base-pairs. The sequence was published in ST Cole et al 'Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence', Nature, 393 (1998), 537-44. By sequencing the genome of the bacteria scientists hoped to improve knowledge about its biology and to improve therapeutics against tuberculosis, a disease that continues to be a serious challenge in global health.1998-06-11T00:00:00+0000The work was undertaken by scientists at the University of Texas Health Centre in Houston and the Institute for Genomic Research in Rockville, MD. The genome is made up of 1.1 million base pairs of DNA. The work was published in CM Fraser et al, 'Complete genome sequence of Treponema pallidum, the syphilis spirochete', Science, 281/5375 (1998), 375-88.1998-07-17T00:00:00+00001998-08-18T00:00:00+0000The genome of the worm was found to have more than 19,000 genes. The sequence was found to follow those of viruses, several bacteria and a yeast. The project was initiated with the development of a clone-based physical map which was important for undertaking the molecular analysis of genes. The results were published by the C elegans Sequencing Consortium in Science, 282/5396 (1998), 2012-8. 1998-12-11T00:00:00+0000Sequence of the first human chromosome (22) is published. 1999-01-01T00:00:00+0000M Akeson, D Branton, JJ Kasianowicz, E Brandin, DW Deamer (1999) 'Microsecond Time-Scale Discrimination Among Polycytidylic Acid, Polyadenylic Acid, and Polyuridylic Acid as Homopolymers or as Segments Within Single RNA Molecules', Biophysical Journal, 77/6, 3227-33. 1999-12-01T00:00:00+00002000-01-01T00:00:00+0000U.S. President Bill Clinton and the British Prime Minister Tony Blair announced the completion of a rough draft of the human genome. The human genome is now know to have more than 3 billion DNA base pairs. Overall the Human Genome Project took 13 years to complete and cost approximate 50 billion dollars. Findings from the work have allowed researchers to begin to understand the function of genes and proteins and their relationship with disease. 2000-06-26T00:00:00+0000The work was undertaken by an international team of scientists from Europe, the US and Japan. They sequenced the DNA of Arabidopsis thaliana, a flowering weed in the mustard family. The sequenced genome contains 25,498 genes encoding proteins from 11,000 families. The project took 4 years to complete. 2000-12-14T00:00:00+0000A consortium including scientists from Celera Genomics and 13 other organisations published the first consensus sequence of human genome. It was shown to have a 2.91 billion base pair sequence. The project took advantage of the DNA sequencing technique pioneered by Fred Sanger. 2001-02-16T00:00:00+0000The paper included an image showing capture of hairpin of DNA by alpha-haemolysin pore in real-time. W Vercoutere, S Winters-Hilt, H Olsen, DW Deamer, D, Haussler, M, Akeson M (2001) 'Rapid discrimination among individual DNA molecules at single nucleotide resolution using a nanopore instrument', Nature Biotechnology, 19, 248-50.2001-03-01T00:00:00+0000S Howorka, S, Cheley, H Bayley (July 2001) 'Sequence-specific detection of individual DNA strands using engineered nanopores', Nature, 19, 636-392001-07-01T00:00:00+00002002-01-01T00:00:00+0000The virologists Jeronimo Cello, Aniko Paul, and Eckard Wimmer of the State University of New York, Stony Brook reported constructing an almost perfect replica of the polio virus from published sequences of the virus, and its reverse transcription into viral RNA. Their work was first announced online in 'Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template', Nature, (12 July 2002), doi:10.1038/news020708-17. 2002-07-12T00:00:00+0000The genomic sequence was completed for Plasmodium falciparum, the malaria parasite, which carries some 5,300 genes (Celera Genomics) and for malaria Anopheles gambiae, the mosquito's principal vector (TIGR and Sanger Centre). 2002-10-03T00:00:00+0000The Human Genome Project was completed, two years ahead of schedule and at a cost of US$2.7 billion. Most of the government-sponsored sequencing was performed in universities and research centres from the United States, the United Kingdom, Japan, France, Germany. 2003-04-14T00:00:00+0000A microarray chip has a collection of microscopic DNA spots which are attached to a surface. Used to measure the expression of large numbers of genes simultaneously or to genotype multiple regions of a genome, microarray chips are now used for a wide number of clinical applications. The first microarray approved by the FDA was Roche's AmpliChip Cytochrome P450 Genotyping Test. This is designed to find the specific gene types of a patient to work out how they will metabolise certain medicines so as to guide what treatment and dose should be prescribed. 2004-12-23T00:00:00+0000The vision of the company was to develop nanopore sequencing for the highly sensitive detection and sequencing of important molecules.2005-01-01T00:00:00+00002005-12-01T00:00:00+0000Y Astler, O Braha, H Bayley, H (2006) 'Toward Single Molecule DNA Sequencing: Direct identification of ribonucleoside and deoxyribonucleoside 5', Journal American Chemistry Society, 128, 1705-10.2006-01-12T00:00:00+0000 Germ-line cell experiments remain off-limit. Sequence of the last chromosome in the Human Genome Project is published in Nature.2006-05-01T00:00:00+00002006-06-01T00:00:00+0000Launched by the National Institutes of Health, the HMP aimed to generate resources that would enable the comprehensive characterisation of the human microbiome and analysis of its role in human health and disease. Overall the project characterised microbiota from 300 healthy individuals from 5 different sites: nasal passages, oral cavity, skin, gastrointestinal tract, and urogenital tract. 16S rRNA sequencing and metagenomic whole genome shotgun were performed to characterise the complexity of microbial communities at each body site.2007-01-01T00:00:00+00002007-05-01T00:00:00+0000The project was funded by the European Commission to study the link between the genes of the human gut microbiota and human health. It focused on two disorders of increasing importance in Europe - inflammatory bowel disease and obesity. 2008-01-01T00:00:00+0000Ray Wu pioneered the first primer-extension method for DNA sequencing which laid the foundation for the Human Genome Project. He was also instrumental in the application of genetic engineering to agricultural plants to improve their output and resistance to pests, salt and drought. 2008-02-10T00:00:00+00002011-01-01T00:00:00+00002011-03-01T00:00:00+0000The device was announced to successfully decode 48,000-base genome of the Phi X 174 phage at a meeting held by Advances in Genome Biology and Technology in Florida. 2012-02-15T00:00:00+0000Sharon Peacock and Julian Parkhill together with other researchers from the University of Cambridge and the Wellcome Trust Sanger Institute used whole genome sequencing to trace the spread of an outbreak of meticillin resistant Staphylococcus aureus (MRSA) in Rosie Hospital's special care baby unit. Prospective sequencing then led them to screen staff and identify the potential source of infection. The researchers reported that the cost of DNA sequencing for the infection was half of the 10,000 pounds spent by the hospital to combat the outbreak of MRSA.2012-06-01T00:00:00+0000Undertaken at the University of California's Rady Children's Hospital in San Diego, the study involves the sequencing of all the genes of individuals in 118 families with a neurodevelopment problem. 2012-12-01T00:00:00+0000The first to determine the DNA sequence of insulin, Sanger proved proteins have a defined chemical composition. He was also pivotal to the development of the dideoxy chain-termination method for sequencing DNA molecules, known as the Sanger method. This provided a breakthrough in the sequencing of long stretches of DNA in terms of speed and accuracy and laid the foundation for the Human Genome Project.2013-11-19T00:00:00+0000The idea was for researchers to test out the MinION so that the company could improve its capability. 2014-04-01T00:00:00+00002014-06-11T00:00:00+00002015-04-01T00:00:00+00002016-06-01T00:00:00+0000Griffin was a leading expert on viruses that cause cancer. She was the first woman appointed to Royal Postgraduate Medical School, Hammersmith Hospital. In 1980 she completed the sequence of the poliovirus, the longest piece of eukaryotic DNA to be sequenced at that time. She devoted her life to understanding the Epstein-Barr virus, the cause of Burkitt's Lymphoma, a deadly form of cancer. 2016-06-13T00:00:00+0000The test detects circulating tumour DNA. It was investigated using blood samples from 161 patients with stage 2 and 3 melanoma who had received surgery. Results showed that skin cancer was much more likely to return within a year of surgery in patients with faults in either BRAF or NRAS genes. R J Lee et al, 'Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma', Annals of Oncology, mdx717, https://doi.org/10.1093/annonc/mdx7172017-11-03T00:00:00+0000Discovery made as a result of study of 177 members of the Old Order of Amish community in Indiana. S. Khan, et al, 'A null mutation in SERPINE1 protects against biological aging in humans', Science Advances, 3/11 (2017), DOI: 10.1126/sciadv.aao16172017-11-15T00:00:00+0000M Jain et al, 'Nanopore sequencing and assembly of a human genome with ultra-long reads', Nature Biotechnology, 36 (2018), 338-45. 2018-01-29T00:00:00+0000Sulston was a biologist who played a central role in sequencing the genome of the Caenorhabditis elegans, a transparent nematode (roundworm). It was the first animal to have its genome sequenced. Based on his work with the nematode Sulston helped set up the project to sequence the human genome which he did as director of the Sanger Centre. The first draft of the human genome sequence was completed in 2000. Sulston shared the Nobel Prize in 2002 for identifying how genes regulate the life cycle of cells through apoptosis. 2018-03-09T00:00:00+0000The test analyses a group of 21 genes found in breast cancer and works out what the risk is of cancer recurring. A trial supported by the National Cancer Institute with 10,273 patients with the most common forms of breast cancer, showed that the test was highly accurate in determining which women would benefit most from chemotherapy after an operation to remove the cancer and who could be safely spared such treatment. The trial was led by Joseph A Sparano at the Albert Einstein Cancer Center, New York. Results from the trial, presented to the American Society of Clinical Oncology in California in Chicago, were described by doctors as 'practice changing'. The test, called Oncotype DX, was developed by Genomic Health, a Californian diagnostics company. The trial's results were published in JA Sparano, et al, 'Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer', New England Journal of Medicine, 379 (July 12 2018), 111-21. 2018-07-12T00:00:00+0000The project, led by Genomics England in partnership with the NHS, sequenced the DNA of both cancer patients and those with rare disorders. Overall 15,000 cancer patients had their DNA analysed, half of whom went on to take part in a clinical trial or receive targeted treatment. One in four participants with rare diseases who had their genomes sequenced received a diagnosis for the first time, thereby paving the way to getting effective treatment. All the sequencing was carried out by the Wellcome Sanger Institute, near Cambridge, in laboratories run by Illumina, a Californian biotechnology company. 2018-12-05T00:00:00+00002019-01-01T00:00:00+00002019-03-01T00:00:00+0000Known as 'whole exome sequencing', the test makes it possible to scan for around 20,000 human genes in just 27 hours rather than 10 days as was the case previously. The test was developed by South West Genomic Laboratory Hub and enable quick diagnoses of approximately 5,000 rare conditions like cystic fibrosis. 2019-10-01T00:00:00+00002019-12-01T00:00:00+00002020-01-01T00:00:00+00002020-06-10T00:00:00+0000
Date Event People Places
13 Aug 1918Frederick Sanger, twice Nobel Prize winner, bornSangerLaboratory of Molecular Biology
14 Aug 1928Ray Wu was born in Beijing, ChinaWuCornell University
3 Jun 1929Werner Arber was born in Granichen, SwitzerlandArberUniversity of Geneva
23 Jan 1930Beverly Griffin was born in Delhi, Louisiana, USAGriffinImperial College
23 Aug 1931Hamilton O Smith was born in New York City, USASmithJohns Hopkins University, Celera
1932Sanger attends Bryanston School, Dorset, as boarderSanger 
21 Mar 1932Walter Gilbert was born in Boston MA, USAGilbertHarvard University, Biogen
1936 - 1940Sanger takes degree in Natural Sciences at Cambridge UniversitySangerCambridge University
1940 - 1943Sanger studies for a doctorate at Cambridge UniversitySangerCambridge University
27 Mar 1942John E Sulston born in Cambridge, UKSulstonLaboratory of Molecular Biology
1944Sanger starts working on amino acid composition of insulinSangerCambridge University
14 Oct 1946J Craig Venter was born in Salt Lake City, UtahVenterSalt Lake City, Utah
1952First observation of the modification of viruses by bacteriaLuria, HumanUniversity of Illinois
1955Sanger completes the full sequence of amino acids in insulinSangerCambridge University
1957Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing techniqueIngram, SangerCambridge University
1958Sanger awarded his first Nobel Prize in ChemistrySangerCambridge University
1960National Biomedical Research Foundation establishedLedleyGeorgetown University
1960Sanger begins to devise ways to sequence nucleic acids, starting with RNASangerCambridge University
1962Sanger moves to the newly created Laboratory of Molecular Biology in CambridgeSangerLaboratory of Molecular Biololgy
23 Jan 1962Idea of restriction and modification enzymes bornArber, DussoixUniversity of Geneva
1965Transfer RNA is the first nucleic acid molecule to be sequencedHolleyCornell University
1965First comprehensive protein sequence and structure computer data published as 'Atlas of Protein Sequence and Structure'Dayhoff, Ledley, EckNational Biomedical Research Foundation, Georgetown University
1965Ledley publishes Uses of Computers in Biology and MedicineLedleyNational Biomedical Research Foundation
1965Sanger and colleagues publish two-dimension partition sequencing methodSanger, Brownlee, BarrellLaboratory of Molecular Biology
1 Oct 1965Werner Arber predicted restriction enzymes could be used as a labortory tool to cleave DNAArberUniversity of Geneva
1967First automatic protein sequencer developedEdman, BeggSt Vincent's School of Medical Research
1968The first partial sequence of a viral DNA is reportedWu, KaiserCornell University, Stanford University Medical School
1969First principles for PCR publishedKhorana, KleppeUniversity of Wisconsin-Madison
1969New species of bacterium is isolated from hot spring in Yellowstone National Park by Thomas BrockBrockCase Western Reserve University
July 1970First restriction enzyme isolated and characterisedSmith, WilcoxJohns Hopkins University
1971Process called repair replication for synthesising short DNA duplexes and single-stranded DNA by polymerases is publishedKhorana, KleppeMIT
May 1971Complete sequence of bacteriophage lambda DNA reportedWu, TaylorCornell University
December 1971First experiments published demonstrating the use of restriction enzymes to cut DNADanna, NathansJohns Hopkins University
1973The sequencing of 24 basepairs is reportedGilbert, MaxamHarvard University
1975Sanger and Coulson publish their plus minus method for DNA sequencingSanger, CoulsonLaboratory of Molecular Biology
1977Complete sequence of bacteriophage phi X174 DNA determinedSangerLaboratory of Molecular Biology
1977First computer programme written to help with the compilation and analysis of DNA sequence dataMcCallumLaboratory of Molecular Biology
February 1977Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNASanger, Maxam, GilbertHarvard University, Laboratory of Molecular Biology
October 1978Nobel Prize given in recognition of discovery of restriction enzymes and their application to the problems of molecular geneticsArber, Nathans, SmithJohns Hopkins University, University of Geneva
1980Sanger awarded his second Nobel Prize in ChemistrySanger, GilbertHarvard University, Laboratory of Molecular Biology
January 1980European Molecular Biology Laboratory convenes meeting on Computing and DNA SequencesEMBL
1980Polyoma virus DNA sequencedGriffin, Soeda, Arrand, WalshImperial Cancer Research Fund Laboratories
15 Sep 1980Largest nucleic acid sequence database in the world made available free over telephone networkDayhoffNational Biomedical Research Foundation, Georgetown University
1982Whole genome sequencing method is introduced for DNA sequencing 
June 1982NIH agrees to provide US$3.2 million over 5 years to establish and maintain a nucleic sequence database 
1983Sanger retiresSangerLaboratory of Molecular Biology
1983Polymerase chain reaction (PCR) starts to be developed as a technique to amplify DNAMullisCetus Corporation
June 1984Results from PCR experiments start being reportedMullisCetus Corporation
10 Sep 1984First genetic fingerprint revealedJeffreysUniversity of Leicester
March 1985Mullis and Cetus Corporation filed patent for the PCR techniqueMullisCetus Corporation
7 Mar 1985DNA fingerprinting principle laid out JeffreysUniversity of Leicester
17 May 19851st legal case resolved using DNA fingerprintingJeffreysUniversity of Leicester
20 Dec 1985The Polymerase Chain Reaction (PCR) technique was publishedMullisCetus Corporation
1986First machine developed for automating DNA sequencingHood, Smith, HunkapillerCalifornia Institute of Technology, Applied Biosystems
30 Apr 1986Plans for sequencing human genome first laid outGilbert, Watson, Berg 
1988US Congress funds genome sequencing 
April 1988Development of first rapid search computer programme to identify genes in a new sequencePearson, Lipman 
25 May 1989David Deamer draws the first sketch to use a biological pore to sequence DNA 
1 Feb 1990First pitch for US Human Genome Project 
1 Oct 1990Human Genome Project formally launched 
December 1990BRCA1, a single gene on chromosome 17, shown to be responsible for many breast and ovarian cancersKing, Lee, Newman, Morrow, Anderson, HueyUniversity of California Berkeley
21 Dec 1990BRCA1 gene linked with inherited predisposition to cancerKingUniversity of California Berkley
1992GenBank is integrated into the NIH National Center for Biotechnology Information 
1992Genetically engineered alpha-haemolysin pore shown to have potential as a biosensorBayley, Krishnasastry, Walker, KasianowiczWorcester Foundation for Experimental Biology, National Institute of Standards and Technology
1 Mar 1992Method devised to isolate methylated cytosine residues in individual DNA strands providing avenue to undertake DNA methylation genomic sequencing 
December 1992First experiments show potential of alpha-haemolysin pore for nanopore sequencingDeamer, KasianowiczNational Institute of Standards and Technology
17 Mar 1995First patent filed for nanopore sequencingChurch, Deamer, Branton, Balderelli, KasianowiczHarvard University, University of California, National Institute of Standards and Technology
28 Jul 1995First complete genome sequence published for a self-replicating free-living organismVenter, Fleischmann, Adams, White, Clayton, Kirkness, Bult, Tomb, Dougherty, MerrickThe Institute for Genomic Research, Johns Hopkins
1996Complete genome sequence of the first eukaryotic organism, the yeast S. cerevisiae, is published  
1996Pyrosequencing is introduced for DNA sequencingRonaghi, NyrenRoyal Institute of Technology
November 1996First paper published highlighting the potential of nanopore sequencingBranton, Brandin, Deamer, KasianowiczHarvard University, University of California Santa Cruz, National Institute of Science and Technology
May 1998Commercial Human Genome Project launchedVenterCelera Genomics
11 Jun 1998Complete genome sequence of bacteria that causes tuberculosis published Cole, Brosch, Parkhill, Garnier, Churcher, Harris, GordonWellcome Trust Sanger Institute, National Institutes of Health, Technical University of Denmark
17 Jul 1998Genome map published for Treponema pallidum, bacteria that causes syphilisFraser, Norris, Weinstock, White, SuttonInstitute for Genomic Research, University of Texas Health Centre
18 Aug 1998First patent granted for nanopore sequencing (US patent 5,795,782 ) Church, Deamer, Branton, Balderelli, KasianowiczHarvard University, University of California, National Institute of Standards and Technology
11 Dec 1998Publication of complete genome sequence of the nematode worm Caenorhabditis elegansSanger Institute, Washington University
1999First human chromosome sequence published 
December 1999Term 'nanopore' used for first time in a publicationAkeson, Branton, Kasianowicz, Brandin, Deamer Harvard University, University of California Santa Cruz, National Institute of Science and Technology
2000Complete sequences of the genomes of the fruit fly Drosophila and the first plant, Arabidopsis, are published 
26 Jun 2000Human genome draft sequence announced 
14 Dec 2000First complete plant genome sequenced 
February 2001First consensus sequence of human genome publishedSanger, Arber, WuLaboratory of Molecular Biology, Celera, Sanger Institute
March 2001Paper published demonstrating possibility of using ion channel to identify individual DNA hairpin moleculesVercoutere, Winters-Hilt, Deamer, Haussler, AkesonUniversity of California Santa Cruz
1 Jul 2001Individual DNA strands, up to 30 nucleotides in length, identified using an engineered nanoporeHoworka, Cheley, BayleyTexas A&M University
2002Complete genome sequence of the first mammalian model organism, the mouse, is published  
12 Jul 2002Polio: First ever virus synthesised from chemicals aloneCello, Paul, WimmerStony Brook University
3 Oct 2002Genomic sequence of the principal malaria parasite and vector completedCelera Genomics, TIGR, Sanger Centre
April 2003The sequence of the first human genome was published 
23 Dec 2004FDA approved first DNA microarray diagnostic device Roche
2005Oxford Nanopore Technology formally registered as a companyBayley, Sabnghera, WillcocksOxford University
December 2005Oxford Nanopore Technology secured two rounds of seed funding from IP Group PlcOxford Nanopore Technology
12 Jan 2006First time four bases of DNA shown to be easily identified using engineered alpha-haemoplysin pore with a molecular adaptorAstler, Braha, BayleyOxford University
May 2006Last human chromosome is sequenced 
June 2006Oxford Nanopore Technology raises £7.7 million from various sources allowing it to expand its teamOxford Nanopore Technology
2007 - 2016Human Microbiome Project (HMP) carried out
May 2007Oxford Nanopore Technology decides to focus its resources on developing nanopore sequencing for DNA sequencingOxford Nanopore Technology
2008 - 2012METAgenomics of the Human Intestinal Tract (MetaHIT) project carried out
10 Feb 2008Ray Wu died in Ithaca, USAWuCornell University
January 2011DNA sequencing proves useful to documenting the rapid evolution of Streptococcus pneumococci in response to the application of vaccinesWellcome Trust Sanger Institute
March 2011Hand-held DNA sequencer (MinION) successfully used to sequence first piece of DNAClive BrownOxford Nanopore Technology
15 Feb 2012 - 18 Feb 2012MinION presented in public for first time Clive BrownOxford Nanopore Technology
June 2012DNA sequencing helps identify the source of an MRSA outbreak in a neornatal intensive care unitPeacock, ParkhillCambridge University, Wellcome Trust Sanger Institute
December 2012DNA sequencing utilised for identifying neurological disease conditions different from those given in the original diagnosisUniversity of California San Diego
19 Nov 2013Fred Sanger, the inventor of DNA sequencing, died at the age of 95SangerCambridge
April 2014Oxford Nanopore Technology released its palm-sized DNA sequencer to researchers through its MinION Access ProgrammeOxford Nanopore Technology
11 Jun 2014Nick Loman successfully used MinION to sequence the genome of the bacterium Pseudomonas aeruginosaLomanUniversity of Birmingham
April 2015 - Oct 2015MinION successfully used to sequence 142 Ebola virus samples in Guinea to help combat outbreak of the diseaseLoman, QuickUniversity of Birmingham
1 Jun 2016Mobile laboratory equipped MinIONS used to sequence and prevent spread of Zika virus in Brazil Quick, de Jesus, Faria, Loman, Goodfellow, RamabutInstituto Evandro Chagas, FIOCRUZ Bahia, ARTIC Network, Oxford Nanopore Technology
13 Jun 2016Beverly Griffin diedGriffinImperial College
3 Nov 2017Research showed simple blood test can identify patients at most risk of skin cancer returningLee, Gremel, Marshall, Myers, Fisher, Dunn, Dhomen, Corrie, Middleton, Lorigan, MaraisUniversity of Manchester
15 Nov 2017Rare mutation of gene called Serpine 1 discovered to protect against biological ageing processKhan, Shah, Klyachko, Baldridge, Eren, Place, Aviv, Puterman, Lloyd-Jones, Heiman, Miyata, Gupta, Shapiro, VaughanNorthwestern University, University of British Columbia, New Jersey Medical School, Tohoku University,
29 Jan 2018MinION shown to be promising tool for sequencing human genomeLoman, Quick, Jain, Koren, Miga, Rand, Sasani, Tyson, Beggs, Dilthey, Fiddes, Malla, Marriot, Nieto, O'Grady, Olsen, Pedersen, Rhie, Richardson, Quinlan, Snutch, Tee, Paten, Philippy, Simpson, LooseUniversity of Birmingham, University of Nottingham, University of Utah, University of British Columbia, University of East Anglia, Ontario Institute for Cancer Research, University of California Santa Cruz, National Human Genome Research Institute
9 Mar 2018John E Sulson diedSulstonLaboratory of Molecular Biology, Sanger Institute
12 Jul 2018Genetic test shown to accurately predict which women benefit from chemotherapySparanoGenomic Health
5 Dec 2018Genomics England completed sequencing 100,000 whole genomesCaulfieldSanger Institute, Illumina
January 2019High throughput nanopore sequencing device (PromethION 48) launched to support population genomics for human sequencing or plant genomicsOxford Nanopore Technology
March 2019ClearLabs launches Food Safety testing using nanopore sequencingOxford Nanopore Technology, ClearLabs
October 2019NHS introduced new fast-track DNA test to scan for rare diseases in babies and childrenSouth West Genomic Laboratory Hub
December 2019Oxford Nanopore Technology's sequencing technology chosen for a population genome genomics programme for the first time (Abu Dhabi Genome Programme)Oxford Nanopore Technology
January 2020Nanopore sequencers begin to be used with ARCTIC protocol to decode the SARS-Cov2 to help combat COVID-19 pandemicLomanOxford Nanopore Technology, ARTIC Network
10 Jun 2020Oxford Nanopore Technology launched its first IVD regulated diagnostic, a highly accurate COVID-19 test called LamPOREOxford Nanopore Technology

13 Aug 1918

Frederick Sanger, twice Nobel Prize winner, born

14 Aug 1928

Ray Wu was born in Beijing, China

3 Jun 1929

Werner Arber was born in Granichen, Switzerland

23 Jan 1930

Beverly Griffin was born in Delhi, Louisiana, USA

23 Aug 1931

Hamilton O Smith was born in New York City, USA

1932

Sanger attends Bryanston School, Dorset, as boarder

21 Mar 1932

Walter Gilbert was born in Boston MA, USA

1936 - 1940

Sanger takes degree in Natural Sciences at Cambridge University

1940 - 1943

Sanger studies for a doctorate at Cambridge University

27 Mar 1942

John E Sulston born in Cambridge, UK

1944

Sanger starts working on amino acid composition of insulin

14 Oct 1946

J Craig Venter was born in Salt Lake City, Utah

1952

First observation of the modification of viruses by bacteria

1955

Sanger completes the full sequence of amino acids in insulin

1957

Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing technique

1958

Sanger awarded his first Nobel Prize in Chemistry

1960

National Biomedical Research Foundation established

1960

Sanger begins to devise ways to sequence nucleic acids, starting with RNA

1962

Sanger moves to the newly created Laboratory of Molecular Biology in Cambridge

23 Jan 1962

Idea of restriction and modification enzymes born

1965

Transfer RNA is the first nucleic acid molecule to be sequenced

1965

First comprehensive protein sequence and structure computer data published as 'Atlas of Protein Sequence and Structure'

1965

Ledley publishes Uses of Computers in Biology and Medicine

1965

Sanger and colleagues publish two-dimension partition sequencing method

1 Oct 1965

Werner Arber predicted restriction enzymes could be used as a labortory tool to cleave DNA

1967

First automatic protein sequencer developed

1968

The first partial sequence of a viral DNA is reported

1969

First principles for PCR published

1969

New species of bacterium is isolated from hot spring in Yellowstone National Park by Thomas Brock

Jul 1970

First restriction enzyme isolated and characterised

1971

Process called repair replication for synthesising short DNA duplexes and single-stranded DNA by polymerases is published

May 1971

Complete sequence of bacteriophage lambda DNA reported

Dec 1971

First experiments published demonstrating the use of restriction enzymes to cut DNA

1973

The sequencing of 24 basepairs is reported

1975

Sanger and Coulson publish their plus minus method for DNA sequencing

1977

Complete sequence of bacteriophage phi X174 DNA determined

1977

First computer programme written to help with the compilation and analysis of DNA sequence data

Feb 1977

Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNA

Oct 1978

Nobel Prize given in recognition of discovery of restriction enzymes and their application to the problems of molecular genetics

1980

Sanger awarded his second Nobel Prize in Chemistry

Jan 1980

European Molecular Biology Laboratory convenes meeting on Computing and DNA Sequences

1980

Polyoma virus DNA sequenced

15 Sep 1980

Largest nucleic acid sequence database in the world made available free over telephone network

1982

Whole genome sequencing method is introduced for DNA sequencing

Jun 1982

NIH agrees to provide US$3.2 million over 5 years to establish and maintain a nucleic sequence database

1983

Sanger retires

1983

Polymerase chain reaction (PCR) starts to be developed as a technique to amplify DNA

Jun 1984

Results from PCR experiments start being reported

10 Sep 1984

First genetic fingerprint revealed

Mar 1985

Mullis and Cetus Corporation filed patent for the PCR technique

7 Mar 1985

DNA fingerprinting principle laid out

17 May 1985

1st legal case resolved using DNA fingerprinting

20 Dec 1985

The Polymerase Chain Reaction (PCR) technique was published

1986

First machine developed for automating DNA sequencing

1986

Plans for sequencing human genome first laid out

1988

US Congress funds genome sequencing

Apr 1988

Development of first rapid search computer programme to identify genes in a new sequence

25 May 1989

David Deamer draws the first sketch to use a biological pore to sequence DNA

25 May 1989

First pitch for US Human Genome Project

1 Oct 1990

Human Genome Project formally launched

Dec 1990

BRCA1, a single gene on chromosome 17, shown to be responsible for many breast and ovarian cancers

21 Dec 1990

BRCA1 gene linked with inherited predisposition to cancer

1992

GenBank is integrated into the NIH National Center for Biotechnology Information

1992

Genetically engineered alpha-haemolysin pore shown to have potential as a biosensor

1 Mar 1992

Method devised to isolate methylated cytosine residues in individual DNA strands providing avenue to undertake DNA methylation genomic sequencing

Dec 1992

First experiments show potential of alpha-haemolysin pore for nanopore sequencing

17 Mar 1995

First patent filed for nanopore sequencing

28 Jul 1995

First complete genome sequence published for a self-replicating free-living organism

1996

Complete genome sequence of the first eukaryotic organism, the yeast S. cerevisiae, is published

1996

Pyrosequencing is introduced for DNA sequencing

Nov 1996

First paper published highlighting the potential of nanopore sequencing

May 1998

Commercial Human Genome Project launched

11 Jun 1998

Complete genome sequence of bacteria that causes tuberculosis published

17 Jul 1998

Genome map published for Treponema pallidum, bacteria that causes syphilis

18 Aug 1998

First patent granted for nanopore sequencing (US patent 5,795,782 )

11 Dec 1998

Publication of complete genome sequence of the nematode worm Caenorhabditis elegans

1999

First human chromosome sequence published

Dec 1999

Term 'nanopore' used for first time in a publication

2000

Complete sequences of the genomes of the fruit fly Drosophila and the first plant, Arabidopsis, are published

26 Jun 2000

Human genome draft sequence announced

14 Dec 2000

First complete plant genome sequenced

Feb 2001

First consensus sequence of human genome published

Mar 2001

Paper published demonstrating possibility of using ion channel to identify individual DNA hairpin molecules

1 Jul 2001

Individual DNA strands, up to 30 nucleotides in length, identified using an engineered nanopore

2002

Complete genome sequence of the first mammalian model organism, the mouse, is published

12 Jul 2002

Polio: First ever virus synthesised from chemicals alone

3 Oct 2002

Genomic sequence of the principal malaria parasite and vector completed

Apr 2003

The sequence of the first human genome was published

23 Dec 2004

FDA approved first DNA microarray diagnostic device

2005

Oxford Nanopore Technology formally registered as a company

Dec 2005

Oxford Nanopore Technology secured two rounds of seed funding from IP Group Plc

12 Jan 2006

First time four bases of DNA shown to be easily identified using engineered alpha-haemoplysin pore with a molecular adaptor

May 2006

Last human chromosome is sequenced

Jun 2006

Oxford Nanopore Technology raises £7.7 million from various sources allowing it to expand its team

2007 - 2016

Human Microbiome Project (HMP) carried out

May 2007

Oxford Nanopore Technology decides to focus its resources on developing nanopore sequencing for DNA sequencing

2008 - 2012

METAgenomics of the Human Intestinal Tract (MetaHIT) project carried out

10 Feb 2008

Ray Wu died in Ithaca, USA

Jan 2011

DNA sequencing proves useful to documenting the rapid evolution of Streptococcus pneumococci in response to the application of vaccines

Mar 2011

Hand-held DNA sequencer (MinION) successfully used to sequence first piece of DNA

15 Feb 2012 - 18 Feb 2012

MinION presented in public for first time

Jun 2012

DNA sequencing helps identify the source of an MRSA outbreak in a neornatal intensive care unit

Dec 2012

DNA sequencing utilised for identifying neurological disease conditions different from those given in the original diagnosis

19 Nov 2013

Fred Sanger, the inventor of DNA sequencing, died at the age of 95

Apr 2014

Oxford Nanopore Technology released its palm-sized DNA sequencer to researchers through its MinION Access Programme

11 Jun 2014

Nick Loman successfully used MinION to sequence the genome of the bacterium Pseudomonas aeruginosa

Apr 2015 - Oct 2015

MinION successfully used to sequence 142 Ebola virus samples in Guinea to help combat outbreak of the disease

1 Jun 2016

Mobile laboratory equipped MinIONS used to sequence and prevent spread of Zika virus in Brazil

13 Jun 2016

Beverly Griffin died

3 Nov 2017

Research showed simple blood test can identify patients at most risk of skin cancer returning

15 Nov 2017

Rare mutation of gene called Serpine 1 discovered to protect against biological ageing process

29 Jan 2018

MinION shown to be promising tool for sequencing human genome

9 Mar 2018

John E Sulson died

12 Jul 2018

Genetic test shown to accurately predict which women benefit from chemotherapy

5 Dec 2018

Genomics England completed sequencing 100,000 whole genomes

Jan 2019

High throughput nanopore sequencing device (PromethION 48) launched to support population genomics for human sequencing or plant genomics

Mar 2019

ClearLabs launches Food Safety testing using nanopore sequencing

Oct 2019

NHS introduced new fast-track DNA test to scan for rare diseases in babies and children

Dec 2019

Oxford Nanopore Technology's sequencing technology chosen for a population genome genomics programme for the first time (Abu Dhabi Genome Programme)

Jan 2020

Nanopore sequencers begin to be used with ARCTIC protocol to decode the SARS-Cov2 to help combat COVID-19 pandemic

10 Jun 2020

Oxford Nanopore Technology launched its first IVD regulated diagnostic, a highly accurate COVID-19 test called LamPORE

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