Genomics

Genomics: timeline of key events

Hamilton O Smith is an American microbiologist who helped isolate and characterised the first restriction enzyme from he 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+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+0000The technique was developed by Mary Weiss and Howard Green. Their method involved fusing a mouse cell that was unable to make the enzyme thymidine kinase with a human cell that could make the enzyme. They then let the cells multiply in a nutrient solution that was deadly to any cells that lacked the enzyme. This killed off all the cells except one clump of identical cells (clone) that produced the enzyme. These cells they found contained the same identical clone. Weiss and Green's technique provided a crucial step towards human gene mapping. Their work was published in 'Human-mouse hybrid cell lines containing partial complements of human chromosomes and functioning human genes', PNAS USA 58/3 (1967): 1104-11. 1967-09-01T00:00:00+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+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+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+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+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 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+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+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+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 device called MiniOn, was developed by Oxford Nanopore Technologies. The company first announced the device to the Advances in Genome Biology and Technology (AGBT) conference in Florida in Feburary 2012. The device measures the change in current resulting from DNA strands interacting with a charged protein nanopore. These measurements are used to determine the nucleotide sequence of the DNA.2014-01-01T00:00:00+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+0000A team of scientists from the UK, USA and Canada showed the device to be useful in tracing infectious diseases like Ebola and the Zika virus in Africa and the US. The device, called the MiniOn sequencer, was developed by Nick Loman and his doctoral student Josh Quick at the University of Birmingham. The device works by passing long strands of DNA through a tiny hole (the eponymous nanopore). Each of strand transmits a unique electrical signal as it passes through the pore, making it possible sequence the 4 bases of the DNA. The method allows for ultra long sequences of DNA to be worked out, 8,000 times longer than a typical sequencing read. It also makes it possible to sequence previously uncharacterised regions of the genome. Details of the research carried out with device were published in M Jain et a, 'Nanopore sequencing and assembly of a human genome with ultra-long reads', Nature Biotechnology, 36 (2018), 338-45.2018-01-29T00:00:00+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+0000
Date Event People Places
23 Aug 1931Hamilton O Smith was born in New York City, USASmithJohns Hopkins University, Celera
14 Oct 1946J Craig Venter was born in Salt Lake City, UtahVenterSalt Lake City, Utah
September 1967Chromosome with a specific gene isolated from hybrid cells produced from fused mouse and human cellsWeiss, GreenNew York University
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 
1 Feb 1990First pitch for US Human Genome Project 
1 Oct 1990Human Genome Project formally launched 
21 Dec 1990BRCA1 gene linked with inherited predisposition to cancerKingUniversity of California Berkley
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
May 1998Commercial Human Genome Project launchedVenterCelera Genomics
17 Jul 1998Genome map published for Treponema pallidum, bacteria that causes syphilisFraser, Norris, Weinstock, White, SuttonInstitute for Genomic Research, University of Texas Health Centre
11 Dec 1998Publication of complete genome sequence of the first multicellular organism, the nematode worm Caenorhabditis elegansSanger Institute, Washington University
1999First human chromosome sequence published 
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 
April 2003The sequence of the first human genome was published 
23 Dec 2004FDA approved first DNA microarray diagnostic device Roche
2014Palm-sized DNA sequencer using nanopore technology made publicly available 
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 2018Handheld device using nanotechnology 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
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

23 Aug 1931

Hamilton O Smith was born in New York City, USA

14 Oct 1946

J Craig Venter was born in Salt Lake City, Utah

Sep 1967

Chromosome with a specific gene isolated from hybrid cells produced from fused mouse and human cells

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

Apr 1988

First pitch for US Human Genome Project

1 Oct 1990

Human Genome Project formally launched

21 Dec 1990

BRCA1 gene linked with inherited predisposition to cancer

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

May 1998

Commercial Human Genome Project launched

17 Jul 1998

Genome map published for Treponema pallidum, bacteria that causes syphilis

11 Dec 1998

Publication of complete genome sequence of the first multicellular organism, the nematode worm Caenorhabditis elegans

1999

First human chromosome sequence published

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

Apr 2003

The sequence of the first human genome was published

23 Dec 2004

FDA approved first DNA microarray diagnostic device

2014

Palm-sized DNA sequencer using nanopore technology made publicly available

15 Nov 2017

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

29 Jan 2018

Handheld device using nanotechnology shown to be promising tool for sequencing human genome

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