DNA sequence from craft to cornerstone
Genomes are the genetic instructions to build an organism: a genome is constructed from genetic letters called DNA bases, and it is the order, or sequence, of those bases that is important for the information in the genome.
At the founding of the Sanger Institute, DNA sequencing was still a cottage industry. Today, thanks to the efforts of the Sanger Institute and other similar institutions, DNA sequence information is no more than a tool, a resource, a part of the fabric of biology that each researcher can rightly assume will be available.
From reading to interpreting
The journey, from hard-won, iconic human genome sequence to an assumed part of the biomedical toolkit, marked the first dozen years of the Sanger Institute's work. Along the way, the Sanger Institute was part of collaborations to sequence the first genome of a model organism (yeast), the first of an animal (nematode worm), and the first human. All were made rapidly and freely available as a mechanism to encourage research by others and to act as a disincentive to the patenting of genes.
Collaborations and consortia
International Human Genome Sequencing Consortium (IHGSC)
The Sanger Institute's leading role in the International Human Genome Sequencing Consortium set us on a path of global large scale collaboration in our science. The Consortium included scientists from 20 institutions around the world and formed the public effort to complete a human genome sequence: this aim was fulfilled in 2003 with the completion of the draft human genome sequence.
International Cancer Genome Consortium (ICGC)
The International Cancer Genome Consortium (ICGC) has been organized to launch and coordinate a large number of research projects that have the common aim of elucidating comprehensively the genomic changes present in many forms of cancers that contribute to the burden of disease in people throughout the world.
HapMap
The International HapMap Project is a partnership of scientists and funding agencies from Canada, China, Japan, Nigeria, the United Kingdom and the United States to develop a public resource that will help researchers find genes associated with human disease and response to pharmaceuticals
Wellcome Trust Case Control Consortium (WTCCC)
The Wellcome Trust Case-Control Consortium (WTCCC) is a group of 50 research groups across the UK which was established in 2005. The WTCCC aims were to exploit progress in understanding of patterns of human genome sequence variation along with advances in high-throughput genotyping technologies, and to explore the utility, design and analyses of genome-wide association (GWA) studies.
1000 Genomes Project
The 1000 Genomes Project is an international research consortium formed to create the most detailed and medically useful picture to date of human genetic variation. The project involves sequencing the genomes of approximately 1200 people from around the world.
The Ensembl Genome Browser
The Ensembl project, jointly run by the Sanger Institute and the European Bioinformatics Institute, produces genome databases for vertebrates and other eukaryotic species, and makes this information freely available online.
MalariaGEN
The international MalariaGEN consortium, founded in 2005, is a key part of our effort to combat the effects of the malaria parasite. The consortium is a data-sharing community of researchers across the globe, including countries directly affected by malaria, which seeks to discover mechanisms of protective immunity to malaria.
Facts and figures
Genome sequences
| Organism | Year completed | Sanger Institute contribution |
|---|---|---|
| Draft Mouse | 2002 | 25% |
| Yeast | 1997 | 66% |
| Caenorhabditis elegans (nematode worm) | 1998 | 50% |
| Mycobacterium tuberculosis (TB) | 1998 | 100% |
| Salmonella Typhi (typhoid) | 2001 | 100% |
| Plasmodium falciperum (malaria parasite) | 2002 | 40% |
| Human | 2003 | 28% |
| MRSA | 2004 | 100% |
| Clostridium difficile | 2006 | 100% |
| Chlamydia trachomatis | 2008 | 100% |
But it is in the understanding of genetic messages that the Sanger Institute seeks to make its greatest contribution. The Sanger Institute has been involved in some of the most exciting discoveries in biomedicine, and its research is among the most highly regarded in the world.
Cited papers
| Authors | Title | Year | Journal | Citations total | Citations p.a. | |
|---|---|---|---|---|---|---|
| 1 | IHGSC | Human Genome Draft | 2001 | Nature | 7244 | 905 |
| 2 | WTCCC | Case Control first results | 2007 | Nature | 859 | 429 |
| 3 | HapMap Consortium | Human Genome HapMap | 2005 | Nature | 1603 | 401 |
| 4 | MGSC | Mouse Genome Draft | 2002 | Nature | 2277 | 325 |
| 5 | Wooster, R. et al | Identification of BRCA2 | 2004 | Nature | 1500 | 300 |
| 6 | Bateman A. et al | The Pfam protein families database | 2004 | Nucleic Acids Research | 1383 | 277 |
| 7 | Bateman A. et al | The pfam protein families database | 2002 | Nucleic Acids Research | 1357 | 194 |
| 8 | Gardner, M.J. et al | Genome sequence of the human malaria parasite Plasmodium falciperum | 2002 | Nature | 1236 | 177 |
| 9 | Kamath R.S. et al | Systematic functional analysis of the Caenorhabditis elegans genome using RNAi | 2003 | Nature | 960 | 160 |
| 10 | Goffeau, A. et al | Life with 6000 genes | 1996 | Science | 1503 | 116 |
| 11 | Wilson, R. et al | 2.2 Mb contiguous nucleotide sequence from chromosome III of C. elegans | 1994 | Nature | 1226 | 82 |
Discoveries
| Discovery | Year |
|---|---|
| A study uncovers six new gene regions associated with increased body mass, five of these are found in the brain. | 2008 |
| New research has defined a mutation in the mouse genome that closely mimics progressive hearing loss in humans. | 2008 |
| Research reveals and catalogues the genomic imbalances in almost 800 cancer cell lines. | 2008 |
| Research suggests that it is not size alone that gives more brain power, but that, during evolution, increasingly sophisticated molecular processing of nerve impulses allowed development of animals with more complex behaviours. | 2008 |
| A study implicates 350 gene regions in cancer development in the mouse. | 2008 |
| A mutated gene was discovered as the key behind families with epilepsy and mental retardation specific to women. The discovery shows that although men can carry the 'bad' gene, only women who carry it are affected. | 2008 |
| Novel method to reveal drug targets: Interactions between proteins studied on a global scale. | 2008 |
| Two genes implicated in the disease ankylosing spondylitis, a common disease primarily causing back pain and progressive stiffness. | 2007 |
| Research from the Wellcome Trust Case Control Consortium played a major part in identifying the clearest genetic link yet to obesity and three new genes linked to type 2 diabetes. | 2007 |
| Mouse microRNA knockout uncovers potential roles in human immune system. | 2007 |
| Researchers provide new insights into autism and learning disability. | 2007 |
| Largest genome study of cancer types shows that the number of mutated genes that drive development of cancer is greater than previously thought. | 2007 |
| For the first time, researchers systematically mapped gene interactions in an animal and identify global properties of genetic interactions to identify common modifiers of human disease genes. | 2006 |
| A genetically modified worm to help screen for drugs. | 2006 |
| Research suggests that losing gene activity can be good for your health: the caspase-12 gene appears to be detrimental to human response to bacterial infection. | 2006 |
| We uncover proteins in synapses that are important in schizophrenia, bipolar disease, mental retardation. | 2006 |
| As part of the HapMap Project, we begin to identify methods to detect regulatory regions of DNA. | 2005 |
| ERBB2 mutation, which controls cell proliferation, is identified as playing a role in 4% of lung cancers. | 2004 |
| BRAF gene is discovered to be implicated in 70% of melanomas. | 2002 |
| BRAC2 breast cancer gene is identified. | 1995 |
DNA in context, in health
Today, the Sanger Institute uses genomic information to understand the role of genes in health and disease: it aims to understand the medical implication of genomics on a scale and with an impact similar to that made by genome sequencing. To understand the biological consequences of genetic variation requires a holistic examination of many biological processes across different systems. Human disease, including heart disease, cancer and diabetes, can result from a complex of interactions of mutations encoded in many genes. At the Sanger Institute, we work on many levels, from looking at genetic patterns in tens of thousands of people, to using mouse models to investigate the effects of individual mutations in individual genes on the organism. Research at these different resolutions will help to develop a more comprehensive understanding of gene function in health and disease and should prove to be the foundation for improvements in patient care.
As part of the Sanger Institute's drive to make real and lasting benefits to global health burdens, we have several teams of researchers dedicated to tackling diseases affecting primarily the developing world. We will complete 10,000 pathogen genomes by the year 2011. In the past, we have been involved in projects to sequence malaria, leishmaniasis, schistosomiasis, sleeping sickness and tuberculosis, all diseases that are massive burden on the developing world. As part of global networks, researchers at the Sanger Institute as well as in the front-line in countries affected, have the opportunity to make steps toward the global eradication of malaria and typhoid.
The postgenomic era opens the door for looking at the impact of genetics of human health. The Sanger Institute will make a contribution in biomedicine and understanding gene function to equal and perhaps eclipse its work in decoding the human and other genomes. Clinical benefits will be a direct result of the kind of research strategy we choose to adopt now.
