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Sequence the Human Genome

Posted in BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, BioTechnology - Venture Creation, Cancer - General, Cancer Informatics, Cerebrovascular and Neurodegenerative Diseases, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Clinical & Translational, Clinical Diagnostics, Clinical Genomics, Computational Biology/Systems and Bioinformatics, Curation, Disease Biology, FDA, Genome Biology, Genomic Testing: Methodology for Diagnosis, Human aging, tagged Craig Venter, human genome, IPad on November 11, 2015| Leave a Comment »

Sequence the Human Genome

Curator: Larry H Bernstein, MD, FCAP

 

 

Geneticist Craig Venter helped sequence the human genome. Now he wants yours.

By CARL ZIMMER   NOVEMBER 5, 2015   http://www.statnews.com/2015/11/05/geneticist-craig-venter-helped-sequence-the-human-genome-now-he-wants-yours/

If you enter Health Nucleus, a new facility in San Diego cofounded by J. Craig Venter, one of the world’s best-known living scientists, you will get a telling glimpse into the state of medical science in 2015.

Your entire genome will be sequenced with extraordinary resolution and accuracy. Your body will be scanned in fine, three-dimensional detail. Thousands of compounds in your blood will be measured. Even the microbes that live inside you will be surveyed. You will get a custom-made iPad app to navigate data about yourself. Also, your wallet will be at least $25,000 lighter.

Venter, who came to the world’s attention in the 1990s when he led a campaign to produce the first draft of a human genome, launched Health Nucleus last month as part of his new company, Human Longevity. He has made clear that his aim is just as lofty as it was when he and his team sequenced the human genome or built a flu vaccine from a genetic sequence delivered to them over the Internet.

“We’re trying to show the value of actual scientific data that can change people’s lives,” Venter told STAT in some of his most extensive remarks yet about the project. “Our goal is to interpret everything in the genome that we can.”

Still, the initiative is drawing deep suspicion among some doctors who question whether Venter’s existing tests can tell patients anything meaningful at all. In interviews, they said they see Health Nucleus as the latest venture that could lead consumers to believe that more testing means improved health. That notion, they say, could drive customers to get procedures they don’t need, which might even be harmful.

“I think there is absolutely no evidence that any of those tests have any benefit for healthy people,” Dr. Rita Redberg, a cardiologist at the University of California at San Diego and the editor-in-chief of JAMA Internal Medicine, said when asked about Venter’s new project.

Venter has a black belt in media savvy — he can make the details of molecular biology alluring for viewers of 60 Minutes and TED talks alike — but off screen he has earned a reputation even from his critics for serious scientific achievements. His non-profit J. Craig Venter Institute, which he founded in 1992, now has a staff of 300. Scientists at the institute have explored everything from the ocean’s biodiversity to the Ebola virus.

Last year, at age 67, Venter cofounded Human Longevity, a company based in San Diego with branches in Mountain View, Calif., and Singapore that is building the largest human genome-sequencing operation on Earth, equipped with massive computing resources to analyze the data being generated. The firm’s database now contains highly accurate genome sequences from 20,000 people; another 3,000 genomes are being added each month.

Franz Och, the former head of Google Translate and an expert on machine learning, is leading a team that’s teaching computers to recognize patterns in the company’s databases that scientists themselves may not be able to see. To demonstrate the power of this approach, Human Longevity researchers are using machine learning to discover how genetic variations shape the human face.

“We can determine a good resemblance of your photograph straight from your genetic code,” said Venter.

Venter and his colleagues will be publishing the results of that study soon — most likely generating another round of headlines. But headlines don’t pay the bills, and at a company that’s got $70 million in funding from private investors, bills matter. The company is now exploring a number of avenues for generating income from its database. It has partnered with Discovery, an insurance company in England and South Africa, to read the DNA of their clients. For $250 apiece, it will sequence the protein-coding regions of the genome, known as exomes, and offer an interpretation of the data.

Health Nucleus could become yet another source of income for Human Longevity. The San Diego facility can handle eight to 12 people a day. There are plans to open more sites both in the United States and abroad. “You can do the math,” Venter said.

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CRACKING THE CODE OF HUMAN LIFE: Milestones along the Way – Part IIA

Posted in Biological Networks, Gene Regulation and Evolution, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, International Global Work in Pharmaceutical, Interviews with Scientific Leaders, Medical and Population Genetics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Scientist: Career considerations, Technology Transfer: Biotech and Pharmaceutical, tagged Cdk2, Cold Spring Harbor Laboratory Press, Craig Venter, cullin ubiquitin ligase family, cyclin E, DNA, DNA damage, ENCODE, F-Box, Fbw7, Gene Regulation, genetics, genomics, Hox gene, Human, human genome, Human Genome Project, National Human Genome Research Institute, Notch propteins, Posttranslational modification, regulatory DNA, ribonucleotide reductase, RNA, RNRs, Science Translational Medicine, shRNA, signal transduction pathways, SNPs, SOS, STAT3, transcription factors on February 12, 2013| 5 Comments »

CRACKING THE CODE OF HUMAN LIFE: Milestones along the Way – Part IIA

Curator: Larry H Bernstein, MD, FCAP

• 

 

Introduction and purpose

This material goes beyond the Initiation Phase of Molecular Biology, Part I.

http://pharmaceuticalintelligence.com/2013/02/08/the-initiation-and-growth-of-molecular-biology-and-genomics/
Part II reviews the Human Genome Project and the decade beyond.

In a three part series:
Part IIA.  CRACKING THE CODE OF HUMAN LIFE: Milestones along the Way
Part IIB.  CRACKING THE CODE OF HUMAN LIFE: The Birth of BioInformatics & Computational Genomics
Part IIC.  CRACKING THE CODE OF HUMAN LIFE: Recent Advances in Genomic Analysis and Disease

Part III will conclude with Ubiquitin, it’s Role in Signaling and Regulatory Control.
Part I reviewed the huge expansion of the biological research enterprise after the Second World War. It concentrated on the

• discovery of cellular structures,
• metabolic function, and
• creation of a new science of Molecular Biology.
•  

Part II follows the race to delineation of the Human Genome, discovery methods and fundamental genomic patterns that are ancient in both animal and plant speciation. But it explores both the complexity and the systems view of the architecture that underlies and understanding of the genome.

These articles review a web-like connectivity between inter-connected scientific discoveries, as significant findings have led to novel hypotheses and many expectations over the last 75 years. This largely post WWII revolution has driven our understanding of biological and medical processes at an exponential pace owing to successive discoveries of

• chemical structure,
• the basic building blocks of DNA  and proteins,
• nucleotide and protein-protein interactions,
• protein folding, allostericity,
• genomic structure,
• DNA replication,
• nuclear polyribosome interaction, and
• metabolic control.

In addition, the emergence of methods for

• copying,
• removal,
• insertion,
• improvements in structural analysis
• developments in applied mathematics that have transformed the research framework.

Part IIA:

CRACKING THE CODE OF HUMAN LIFE:

Milestones along the Way

A NOVA interview with Francis Collins (NHGRI) (FC), J. Craig Venter (CELERA)(JCV), and Eric Lander (EL).
RK: For the past ten years, scientists all over the world have been painstakingly trying to read the tiny instructions buried inside our DNA. And now, finally, the “Human Genome” has been decoded.
EL: The genome is a storybook that’s been edited for a couple billion years.
The following will address the odd similarity of genes between man and yeast

EL: In the nucleus of your cell the DNA molecule resides that is about 10 angstroms wide curled up, but the amount of curling is limited by the negative charges that repel one another, but there are folds upon folds. If the DNA is stretched the length of the DNA would be thousands of feet.
EL: We have known for 2000 years that your kids look a lot like you. Well it’s because you must pass them instructions that give them the eyes, the hair color, and the nose shape they have. RK: Cracking the code of those minuscule differences in DNA that influence health and illness is what the Human Genome Project is all about. Since 1990, scientists all over the world have been involved in the effort to read all three billion As, Ts, Gs, and Cs of human DNA.  It took 10 years to find the one genetic mistake that causes cystic fibrosis. Another 10 years to find the gene for Huntington’s disease. Fifteen years to find one of the genes that increase the risk for breast cancer. One letter at a time, painfully slowly…     And then came the revolution. In the last ten years the entire process has been computerized. The computations can do a thousand every second and that has made all the difference. EL: This is basically a parts list with a lot of parts. If you take an airplane, a Boeing 777, I think it has like 100,000 parts. If I gave you a parts list for the Boeing 777 in one sense you’d know 100,000 components, screws and wires and rudders and things like that.  But you wouldn’t know how to put it together, or why it flies. We now have a parts list, and that’s not enough to understand why it flies.

The Human Genome (Photo credit: dullhunk)

A Quest For Clarity

Tracy Vence is a senior editor of Genome Technology
Tracy Vence @GenomeTechMag
Projects supported by the US National Institutes of Health will have produced 68,000 total human genomes — around 18,000 of those whole human genomes — through the end of this year, National Human Genome Research Institute estimates indicate. And in his book, The Creative Destruction of Medicine, the Scripps Research Institute’s Eric Topol projects that 1 million human genomes will have been sequenced by 2013 and 5 million by 2014.
Daniel MacArthur, a group leader in Massachusetts General Hospital’s Analytic and Translational Genetics Unit estimates that “From a capacity perspective … millions of genomes are not that far off. If you look at the rate that we’re scaling, we can certainly achieve that.”    The prospect of so many genomes has brought clinical interpretation into focus. But there is an important distinction to be made between the interpretation of an apparently healthy person’s genome and that of an individual who is already affected by a disease.
In an April Science Translational Medicine paper, Johns Hopkins University School of Medicine‘s Nicholas Roberts and his colleagues reported that personal genome sequences for healthy monozygotic twin pairs are not predictive of significant risk for 24 different diseases in those individuals. The researchers concluded that whole-genome sequencing was not likely to be clinically useful. Ambiguities have clouded even the most targeted interpretation efforts.

• Technological challenges,
• meager sample sizes,
• a need for increased,
• fail-safe automation and most important
• a lack of community-wide standards for the task.

have hampered researchers’ attempts to reliably interpret the clinical significance of genomic variation.

How signals from the cell surface affect transcription of genes in the nucleus.

 

James Darnell, Jr., MD, Astor Professor, Rockefeller
After graduation from Washington University School of Medicine he worked with Francois Jacob at the Pasteur Institute in Paris and served as Vice President for Academic Affairs at Rockefeller in 1990-91. He is the coauthor with S.E. Luria of General Virology and the founding author with Harvey Lodish and David Baltimore of Molecular Cell Biology, now in its sixth edition. His book RNA, Life’s Indispensable Molecule was published in July 2011 by Cold Spring Harbor Laboratory Press. A member of the National Academy of Sciences since 1973, recipient of  numerous awards, including the 2003 National Medal of Science, the 2002 Albert Lasker Award.
Using interferon as a model cytokine, the Darnell group discovered that cell transcription was quickly changed by binding of cytokines to the cell surface. The bound interferon led to the tyrosine phosphorylation of latent cytoplasmic proteins now called STATs (signal transducers and activators of transcription) that dimerize by

• reciprocal phosphotyrosine-SH2 interchange.
• accumulate in the nucleus,
• bind DNA and drive transcription.

This pathway has proved to be of wide importance with seven STATs now known in mammals that take part in a wide variety of developmental and homeostatic events in all multicellular animals. Crystallographic analysis defined functional domains in the STATs, and current attention is focused on two areas:

• how the STATs complete their cycle of  activation and inactivation, which requires regulated tyrosine dephosphorylation; and how
• persistent activation of STAT3 that occurs in a high proportion of many human cancers contributes to blocking apoptosis in cancer cells.

Current efforts are devoted to inhibiting STAT3 with modified peptides that can enter cells.

Cell cycle regulation and the cellular response to genotoxic stress

Stephen J Elledge, PhD, Gregor Mendel Professor of Genetics and Medicine, Investigator, Howard Hughes Medical Institute, Harvard Medical School
As a postdoctoral fellow at Stanford working on eukaryotic homologous recombination, he serendipitously found a family of genes known as ribonucleotide reductases. He subsequently showed that

• these genes are activated by DNA damage and
• could serve as tools to help scientists dissect the signaling pathways
• through which cells sense and respond to DNA damage and replication stress.

At Baylor College of Medicine he made a second major breakthrough with the discovery of the cyclin-dependent kinase 2 gene (Cdk2), which

• controls the G1-to-S cell cycle transition,
• an entry checkpoint for the cell proliferation cycle and
• a critical regulatory step in tumorigenesis.

From there, using a novel “two-hybrid” cloning method he developed, Elledge and Wade Harper, PhD, proceeded to

• isolate several members of the Cdk2-inhibitory family.

Their discoveries included the p21 and p57 genes, mutations in the latter (responsible for Beckwith-Wiedemann syndrome), characterized by somatic overgrowth and increased cancer risk. Elledge is also recognized for his work in understanding

• proteome remodeling through ubiquitin-mediated proteolysis.
• they identified F-box proteins that regulate protein degradation in the cell by

1. binding to specific target protein sequences and then
2. marking them with ubiquitin for destruction by the cell’s proteasome machinery.

This breakthrough resulted in

• the elucidation of the cullin ubiquitin ligase family,
• which controls regulated protein stability in eukaryotes.

  

Elledge’s recent research has focused on the cellular mechanisms underlying DNA damage detection and cancer using genetic technologies. In collaboration with Cold Spring Harbor Laboratory researcher Gregory Hannon, PhD, Elledge has generated complete human and mouse short hairpin RNA (shRNA) libraries for genome-wide loss-of-function studies. Their efforts have led to

• the identification of a number of tumor suppressor proteins
• genes upon which cancer cells uniquely depend for survival.

This work led to the development of the “non-oncogene addiction” concept. This is noted as follows:

• proteome remodeling through ubiquitin-mediated proteolysis
• F-box proteins regulate protein degradation in the cell by binding to specific target protein sequences
• and then marking them with ubiquitin for destruction by the cell’s proteasome machinery
• elucidation of the cullin ubiquitin ligase family, which controls regulated protein stability in eukaryotes

Playing the dual roles of inventor and investigator, Elledge developed original techniques to define

• what drives the cell cycle and
• how cells respond to DNA damage.

By using these tools, he and his colleagues have identified multiple genes involved in cell-cycle regulation.

Elledge’s work has earned him many awards, including a 2001 Paul Marks Prize for Cancer Research and a 2003 election to the National Academy of Sciences. In his Inaugural Article (1), published in this issue of PNAS, Elledge and his colleagues describe the function of Fbw7, a protein involved in controlling cell proliferation (see below). Elledge studied the error-prone DNA repair mechanism in E-Coli (Escherichia coli) called SOS mutagenesis for his PhD thesis at MIT. His work identified  and described

• the regulation of a group of enzymes now known as error-prone polymerases,
• the first members of which were the umuCD genes in E. coli.

It was then that he developed a new cloning tool. Elledge invented a technique that allowed him to approach future cloning problems of this type with great rapidity. With the new technique, “you could make large libraries in lambda that behave like plasmids. We called them `phasmid’ vectors, like plasmid and phage together”. The phasmid cloning method was an early cornerstone for molecular biology research.

Elledge began working on homologous recombination in postdoctoral fellowship at Stanford University, an important niche in the field of eukaryotic genetics. Working with the yeast genome, Elledge searched for rec A, a gene that allows DNA to recombine homologously. Although he never located rec A, he discovered a family of genes known as ribonucleotide reductases (RNRs), which are involved in DNA production. Rec A and RNRs share the same last 4 amino acids, which caused an antibody crossreaction in one of Elledge’s experiments. Initially disappointed with the false positives in his hunt for rec A, Elledge was later delighted with his luck. He found that

• RNRs are turned  on by DNA damage, and
• these genes are regulated by the cell cycle.

Prior to leaving Stanford, Elledge attended a talk at the University of California, San Francisco, by Paul Nurse, a leader in cell-cycle research who would later win the 2001 Nobel Prize in medicine. Nurse described his success in isolating the homolog of a key human cell-cycle kinase gene, Cdc2, by using a mutant strain of yeast (8). Although Nurse’s methods were primitive, Elledge was struck by the message he carried: that

• cell-cycle regulation was functionally conserved, and
• many human genes could be isolated by looking for complimentary genes in yeast.

Elledge then took advantage of his past successes in building phasmid vectors to build a versatile human cDNA library that could be expressed in yeast. After setting up a laboratory at Baylor, he introduced this library into yeast, screening for complimentary cell-cycle genes.  He quickly identified the same Cdc2 gene isolated by Nurse. However, Elledge also discovered a related gene known as Cdk2. Elledge subsequently found that

• Cdk2 controlled the G1 to S cell-cycle transition, a step that often goes awry in cancer. These results were published in the EMBO Journal in 1991.

He then continued to use

• RNRs to perform genetic screens to
• identify genes involved in sensing and responding to DNA damage.

He subsequently worked out the

• signal transduction pathways in both yeast and humans that recognize damaged DNA and replication problems.

These “checkpoint” pathways are central to the

• prevention of genomic instability and a key to understanding tumorigenesis.

This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected on April 29, 2003.

Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein.

Tetzlaff MT, Yu W, Li M, Zhang P, Finegold M, Mahon K , Harper JW, Schwartz RJ, and SJ Elledge. PNAS 2004; 101(10): 3338-3345. cgi doi 10.1073.  pnas.0307875101

The mammalian F-box protein Fbw7 and its Caenorhabditis elegans counterpart Sel-10 have been implicated in

• the ubiquitin-mediated turnover of cyclin E
• as well as the Notch Lin-12 family of transcriptional activators. Both unregulated

1. Notch and cyclin E
2. promote tumorigenesis, and
3. inactivate mutations in human

Fbw7 studies suggest that it may be a tumor suppressor. To generate an in vivo system to assess the consequences of such unregulated signaling, we generated mice deficient for Fbw7.  Fbw7-null mice die around 10.5 days post coitus because of a combination of deficiencies in hematopoietic and vascular development and heart chamber mutations. The absence of Fbw7 results in elevated levels of cyclin E, concurrent with inappropriate DNA replication in placental giant trophoblast cells. Moreover, the levels of both Notch 1 and Notch 4 intracellular domains were elevated, leading to stimulation of downstream transcriptional pathways involving Hes1, Herp1, and Herp2. These data suggest essential functions for Fbw7 in controlling cyclin E and Notch signaling pathways in the mouse.

Science as an Adventure

Ubiquitins

Prof. Avram Hershko – Science as an Adventure
Prof. Avram Hershko shared the 2004 Nobel Prize in Chemistry with Aaron Ciechanover and Irwin Rose for “for the discovery of ubiquitin-mediated protein degradation.”

http://www.youtube.com/watch?v=lGJvsmG3mhw&feature=player_detailpage&list=EC8814C902ACB98559

Gene Switches

Nipam Patel is a professor in the Departments of Molecular and Cell Biology and Integrative Biology at UC Berkeley and runs a research laboratory that studies the role, during embryonic development, of homeotic genes (the genetic switches described in this feature). “Ghost in Your Genes” focuses on epigenetic “switches” that turn genes “on” or “off.” But not all switches are epigenetic; some are genetic. That is, other genes within the chromosome turn genes on or off. In an animal’s embryonic stage, these gene switches play a predominant role in laying out the animal’s basic body plan and perform other early functions;

• the epigenome begins to take over during the later stages of embryogenesis.

Beginning as a fertilized single egg that egg becomes many different kinds of cells.  Altogether, multicellular organisms like humans have thousands of differentiated cells. Each is optimized for use in the brain, the liver, the skin, and so on. Remarkably, the DNA inside all these cells is exactly the same. What makes the cells differ from one another is that different genes in that DNA are either turned on or off in each type of cell.

Take a typical cell, such as a red blood cell. Each gene within that cell has a coding region that encodes the information used to make a particular protein. (Hemoglobin shuttles oxygen to the tissues and carbon dioxide back out to the lungs—or gills, if you’re a fish.) But another region of the gene, called “regulatory DNA,” determines whether and when the gene will be expressed, or turned on, in a particular kind of cell. This precise transcribing of genes is handled by proteins known as transcription factors, which bind to the regulatory DNA, thereby generating instructions for the coding region.

One important class of transcription factors is encoded by the so called homeotic, or Hox, genes. Found in all animals, Hox genes act to “regionalize” the body along the embryo’s anterior-to-posterior (head-to-tail) axis. In a fruit fly, for example, Hox genes lay out the various main body segments—the head, thorax, and abdomen. Amazingly, all animals, from fruit flies to mice to people, rely on the same basic Hox-gene complex. Using different-colored antibody stains, we can see exactly where and to what degree Hox genes are expressed. Each Hox gene is expressed in a specific region along the anterior-to-posterior axis of the embryo.

A fly’s body has three main divisions: head, thorax, and abdomen. We’ll focus on the thorax, which itself has three main segments. In a normal adult fly, the second thoracic segment features a pair of wings, while the third thoracic segment has a pair of small, balloon-shaped structures called halteres. A modified second wing, the haltere serves as a flight stabilizer. In order for the pair of wings and the pair of halteres (as well as all other parts of the fly) to develop properly, the fly’s suite of

• Hox genes must be expressed in a precise way and at precise times.

During development, the fly’s two wings grow from a structure in the larva known as the wing imaginal disk. (An imago is an insect in its final, adult state.) The haltere grows from the larval haltere imaginal disk. Remember the Ubx Hox gene? Using staining again, we can detect the gene product of Ubx. This reveals that

• the Ubx gene is naturally “off” in the wing disk—
• and is “on” in the haltere disk.
• Now you’ll see what happens when the Ubx gene—just one of a large number of Hox genes—is turned off in the haltere disk. What if a genetic mutation caused the Ubx gene to be turned off, during the larval stage, in the third thoracic segment, the segment that normally produces the haltere? Instead of a pair of halteres, the fly has a second set of wings. With the switch of that single Hox gene, Ubx, from on to off, the third thoracic segment becomes an additional second thoracic segment and the pair of halteres became a second pair of wings. This illustrates the remarkable ability of transcription factors like Ubx to control patterning as well as cell type during development.

ENCODE

A. Data Suggests “Gene” Redefinition

As part of a huge collaborative effort called ENCODE (Encyclopedia of DNA Elements), a research team led by Cold Spring Harbor Laboratory (CSHL) Professor Thomas Gingeras, PhD, publishes a genome-wide analysis of RNA messages, called transcripts, produced within human cells.
Their analysis—one component of a massive release of research results by ENCODE teams from 32 institutes in 5 countries, with 30 papers appearing in 3 different high-level scientific journals—shows that three-quarters of the genome is capable of being transcribed.  This indicates that nearly all of our genome is dynamic and active.  It stands in marked contrast to consensus views prior to ENCODE’s comprehensive research efforts, which suggested that

• only the small protein-encoding fraction of the genome was transcribed.

The vast amount of data generated with advanced technologies by Gingeras’ group and others in the ENCODE project changes the prevailing understanding of what defines a gene. The current outstanding question concerns

• the nature and range of those functions.  It is thought that these
• “non-coding” RNA transcripts act something like components of a giant, complex switchboard, controlling a network of  many events in the cell by

1. regulating the processes of
2. replication,
3. transcription
4. and translation

– that is, the copying of DNA and the making of proteins is based on information carried by messenger RNAs.  With the understanding that so much of our DNA can be transcribed into RNA comes the realization that there is much less space between what we previously thought of as genes, Gingeras points out.

The full ENCODE Consortium data sets can be freely accessed through

• the ENCODE project portal as well as at the University of California at Santa Cruz genome browser,
• the National Center for Biotechnology Information, and
• the European Bioinformatics Institute.

Topic threads that run through several different papers can be explored via the ENCODE microsite page at http://Nature.com/encode.    Date: September 5, 2012   Source: Cold Spring Harbor Laboratory

1000 Genomes Project Team Reports on Variation Patterns

(from Phase I Data) October 31, 2012 GenomeWeb

In a study appearing online today in Nature, members of the 1000 Genomes Project Consortium presented an integrated haplotype map representing the genomic variation present in more than 1,000 individuals from 14 human populations.  Using data on 1,092 individuals tested by

• low-coverage whole-genome sequencing,
• deep exome sequencing, and/or
• dense genotyping,

the team looked at the nature and extent of the rare and common variation present in the genomes of individuals within these populations. In addition to population-specific differences in common variant profiles, for example, the researchers found distinct rare variant patterns within populations from different parts of the world — information that is expected to be important in interpreting future disease studies. They also encountered a surprising number of the variants that are expected to impact gene function, such as

• non-synonymous changes,
• loss-of-function variants, and, in some cases,
• potentially damaging mutations.

ENCODE was designed to pick up where the Human Genome Project left off.
Although that massive effort revealed the blue­print of human biology, it quickly became clear that the instruction manual for reading the blueprint was sketchy at best. Researchers could identify in its 3 billion letters many of the regions that code for proteins, but they make up little more than 1% of the genome, contained in around 20,000 genes. ENCODE, which started in 2003, is a massive data-collection effort designed to catalogue the

• ‘functional’ DNA sequences,
• learn when and in which cells they are active and
• trace their effects on how the genome is

1. packaged,
2. regulated and
3. read.

After an initial pilot phase, ENCODE scientists started applying their methods to the entire genome in 2007. That phase came to a close with the publication of 30 papers, in Nature, Genome Research and Genome Biology. The consortium has assigned some sort of function to roughly 80% of the genome, including

• more than 70,000 ‘promoter’ regions — the sites, just upstream of genes, where proteins bind to control gene expression —
• and nearly 400,000 ‘enhancer’ regions that regulate expression of  distant genes (see page 57)1. But the job is far from done.

Junk DNA? What Junk DNA?

New data reveals that at least 80% of the human genome encodes elements that have some sort of biological function. [© Gernot Krautberger – Fotolia.com] Far from containing vast amounts of junk DNA between its protein-coding genes, at least 80% of the human genome encodes elements that have some sort of biological function, according to newly released data from the Encyclopedia of DNA Elements (Encode) project, a five-year initiative that aims to delineate all functional elements within human DNA. The massive international project, data from which are published in 30 different papers in Nature, Genome Research, Genome Biology, the Journal of Biological Chemistry, Science, and Cell, has identified four million gene switches, effectively

• regulatory regions in the genome where
• proteins interact with the DNA to control gene expression.

Overall, the Encode data define regulatory switches that are scattered all over the three billion nucleotides of the genome. In fact, the data suggests,

• the regions that lie between gene-coding sequences contain a wealth of previously unrecognized functional elements,Including
• nonprotein-coding RNA transcribed sequences,
• transcription factor binding sites,
• chromatin structural elements, and
• DNA methylation sites.

The combined results suggest that 95% of the genome lies within 8 kb of a DNA-protein interaction, and 99% lies within 1.7 kb of at least one of the biochemical events, the researchers say. Importantly, given the complex three-dimensional nature of DNA, it’s also apparent that

• a regulatory element for one gene may be located quite some ‘linear’ distance from the gene itself.

“The information processing and the intelligence of the genome reside in the regulatory elements,” explains Jim Kent, director of the University of California, Santa Cruz Genome Browser project and head of the Encode Data Coordination Center. “With this project, we probably went from understanding less than 5% to now around 75% of them.”
The ENCODE results also identified SNPs within regulatory regions that are associated with a range of diseases, providing new insights into the roles that

• noncoding DNA plays in disease development.

“As much as nine out of 10 times, disease-linked genetic variants are not in protein-coding regions,” comments Mike Pazin, Encode program director at the National Human Genome Research Institute.  “Far from being junk DNA, this regulatory DNA clearly makes important contributions to human disease.”

Other Related Articles on this Open Access Online Scientific Journal, include the following: 

 

Big Data in Genomic Medicine LHB

http://pharmaceuticalintelligence.com/2012/12/17/big-data-in-genomic-medicine/

BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair S Saha
http://pharmaceuticalintelligence.com/2012/12/04/brca1-a-tumour-suppressor-in-breast-and-ovarian-cancer-functions-in-transcription-ubiquitination-and-dna-repair/

Computational Genomics Center: New Unification of Computational Technologies at Stanford A Lev-Ari
http://pharmaceuticalintelligence.com/2012/12/03/computational-genomics-center-new-unification-of-computational-technologies-at-stanford/

Personalized medicine gearing up to tackle cancer ritu saxena
http://pharmaceuticalintelligence.com/2013/01/07/personalized-medicine-gearing-up-to-tackle-cancer/

Differentiation Therapy – Epigenetics Tackles Solid Tumors sj Williams
http://pharmaceuticalintelligence.com/2013/01/03/differentiation-therapy-epigenetics-tackles-solid-tumors/

Mechanism involved in Breast Cancer Cell Growth: Function in Early Detection & Treatment A Lev-Ari
http://pharmaceuticalintelligence.com/2013/01/17/mechanism-involved-in-breast-cancer-cell-growth-function-in-early-detection-treatment/

The Molecular pathology of Breast Cancer Progression tilde barliya`
http://pharmaceuticalintelligence.com/2013/01/10/the-molecular-pathology-of-breast-cancer-progression/

Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1 (pharmaceuticalintelligence.com) A Lev-Ari

http://pharmaceuticalintelligence.com/2013/01/13/paradigm-shift-in-human-genomics-predictive-biomarkers-and-personalized-medicine-part-1/

LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2 A Lev-Ari
http://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer-personalized-treatment-part-2/

Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3 A Lev-Ari
http://pharmaceuticalintelligence.com/2013/01/13/personalized-medicine-an-institute-profile-coriell-institute-for-medical-research-part-3/

Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders @ http://pharmaceuticalintelligence.com ALA
http://pharmaceuticalintelligence.com/2013/01/13/7000/Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders/

GSK for Personalized Medicine using Cancer Drugs needs Alacris systems biology model to determine the in silico effect of the inhibitor in its “virtual clinical trial” A Lev-Ari
http://pharmaceuticalintelligence.com/2012/11/14/gsk-for-personalized-medicine-using-cancer-drugs-needs-alacris-systems-biology-model-to-determine-the-in-silico-effect-of-the-inhibitor-in-its-virtual-clinical-trial/

Recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes in serous endometrial tumors S Saha
http://pharmaceuticalintelligence.com/2012/11/19/recurrent-somatic-mutations-in-chromatin-remodeling-and-ubiquitin-ligase-complex-genes-in-serous-endometrial-tumors/

Personalized medicine-based cure for cancer might not be far away ritu saxena
http://pharmaceuticalintelligence.com/2012/11/20/personalized-medicine-based-cure-for-cancer-might-not-be-far-away/

Human Variome Project: encyclopedic catalog of sequence variants indexed to the human genome sequence A Lev-Ari
http://pharmaceuticalintelligence.com/2012/11/24/human-variome-project-encyclopedic-catalog-of-sequence-variants-indexed-to-the-human-genome-sequence/

Prostate Cancer Cells: Histone Deacetylase Inhibitors Induce Epithelial-to-Mesenchymal Transition sjwilliams
http://pharmaceuticalintelligence.com/2012/11/30/histone-deacetylase-inhibitors-induce-epithelial-to-mesenchymal-transition-in-prostate-cancer-cells/

Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics A Lev-Ari
http://pharmaceuticalintelligence.com/2013/01/10/inspiration-from-dr-maureen-cronins-achievements-in-applying-genomic-sequencing-to-cancer-diagnostics/

The “Cancer establishments” examined by James Watson, co-discoverer of DNA w/Crick, 4/1953 A Lev-Ari
http://pharmaceuticalintelligence.com/2013/01/09/the-cancer-establishments-examined-by-james-watson-co-discover-of-dna-wcrick-41953/

Directions for genomics in personalized medicine lhb
http://pharmaceuticalintelligence.com/2013/01/27/directions-for-genomics-in-personalized-medicine/

How mobile elements in “Junk” DNA promote cancer. Part 1: Transposon-mediated tumorigenesis. SJwilliams
http://pharmaceuticalintelligence.com/2012/10/31/how-mobile-elements-in-junk-dna-prote-cancer-part1-transposon-mediated-tumorigenesis/

Mitochondria: More than just the “powerhouse of the cell” eritu saxena
http://pharmaceuticalintelligence.com/2012/07/09/mitochondria-more-than-just-the-powerhouse-of-the-cell/

Mitochondrial fission and fusion: potential therapeutic targets? Ritu saxena
http://pharmaceuticalintelligence.com/2012/10/31/mitochondrial-fission-and-fusion-potential-therapeutic-target/

Mitochondrial mutation analysis might be “1-step” away ritu saxena
http://pharmaceuticalintelligence.com/2012/08/14/mitochondrial-mutation-analysis-might-be-1-step-away/

mRNA interference with cancer expression lhb
http://pharmaceuticalintelligence.com/2012/10/26/mrna-interference-with-cancer-expression/

Expanding the Genetic Alphabet and linking the genome to the metabolome LHB
http://pharmaceuticalintelligence.com/2012/09/24/expanding-the-genetic-alphabet-and-linking-the-genome-to-the-metabolome/

Breast Cancer, drug resistance, and biopharmaceutical targets lhb
http://pharmaceuticalintelligence.com/2012/09/18/breast-cancer-drug-resistance-and-biopharmaceutical-targets/

Breast Cancer: Genomic profiling to predict Survival: Combination of Histopathology and Gene Expression Analysis A Lev-Ari
http://pharmaceuticalintelligence.com/2012/12/24/breast-cancer-genomic-profiling-to-predict-survival-combination-of-histopathology-and-gene-expression-analysis/

Gastric Cancer: Whole-genome reconstruction and mutational signatures A Lev-Ari
http://pharmaceuticalintelligence.com/2012/12/24/gastric-cancer-whole-genome-reconstruction-and-mutational-signatures-2/

Ubiquinin-Proteosome pathway, autophagy, the mitochondrion, proteolysis and cell apoptosis lhb
http://pharmaceuticalintelligence.com/2012/10/30/ubiquinin-proteosome-pathway-autophagy-the-mitochondrion-proteolysis-and-cell-apoptosis/

Genomic Analysis: FLUIDIGM Technology in the Life Science and Agricultural Biotechnology A Lev-Ari
http://pharmaceuticalintelligence.com/2012/08/22/genomic-analysis-fluidigm-technology-in-the-life-science-and-agricultural-biotechnology/

Reveals from ENCODE project will invite high synergistic collaborations to discover specific targets A. Sarkar

http://pharmaceuticalintelligence.com/2012/09/30/reveals-from-encode-project-will-lead-to-confusion-or-specific-target/

ENCODE: the key to unlocking the secrets of complex genetic diseases R. Saxena

http://pharmaceuticalintelligence.com/2012/09/26/encode-the-key-to-unlocking-the-secrets-of-complex-genetic-diseases/

Impact of evolutionary selection on functional regions: The imprint of evolutionary selection on ENCODE regulatory elements is manifested between species and within human populations s Saha

http://pharmaceuticalintelligence.com/2012/09/20/impact-of-evolutionary-selection-on-functional-regions-the-imprint-of-evolutionary-selection-on-encode-regulatory-elements-is-manifested-between-species-and-within-human-populations/

ENCODE Findings as Consortium A Lev-Ari

http://pharmaceuticalintelligence.com/2012/09/10/encode-findings-as-consortium/

Genomics Orientations for Personalized Medicine SJH, ALA, LHB

http://pharmaceuticalintelligence.com/biomed-e-books/genomics-orientations-for-personalized-medicine/

2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

http://pharmaceuticalintelligence.com/2013/02/11/2013-genomics-the-era-beyond-the-sequencing-human-genome-francis-collins-craig-venter-eric-lander-et-al/

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2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

Posted in Biological Networks, Gene Regulation and Evolution, Cardiovascular Pharmacogenomics, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Genome Biology, Genomic Testing: Methodology for Diagnosis, Interviews with Scientific Leaders, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Proteomics, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Scientist: Career considerations, Technology Transfer: Biotech and Pharmaceutical, tagged Craig Venter, DNA Sequencing, Francis Collins, genetics, Genomic, human genome, Human Genome Project on February 11, 2013| 14 Comments »

2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

Curator: Aviva Lev-Ari, PhD, RN

• 

 

One decade following the completion of the  Sequencing of the Human Genome — the field of Genomics, the discipline that has emerged as a result of project completion has FOUR concentrations:

COMPARATIVE GENOMICS

Genomes of Other Organisms: DNA Barcoding and Metagenomics

 

Interpreting Shared Characteristics: The Platypus Genome

 

Microarray-based Comparative Genomic Hybridization (aCGH)

 

Pufferfish and Ancestral Genomes

 

Simple Viral and Bacterial Genomes

GENOME SEQUENCING AND ANNOTATION

Basic Local Alignment Search Tool (BLAST)

 

Complex Genomes: Shotgun Sequencing

 

DNA Sequencing Technologies

 

DNA Sequencing Technologies Key to the Human Genome Project

 

Genomic Data Resources: Challenges and Promises

 

Sequencing Human Genome: the Contributions of Francis Collins and Craig Venter

FUNCTIONAL GENOMICS

Microarray-based Comparative Genomic Hybridization (aCGH)

 

Ontologies: Scientific Data Sharing Made Easy

 

The Proteome: Discovering the Structure and Function of Proteins

 

Transcriptome: Connecting the Genome to Gene Function

 

TRANSLATIONAL GENOMICS

 

Behavioral Genomics

 

Comparative Methylation Hybridization

 

DNA Fingerprinting Using Amplified Fragment Length Polymorphisms (AFLP)

 

Epigenomics: The New Tool in Studying Complex Diseases

 

Pharmacogenomics and Personalized Medicine

 

Sustainable Bioenergy: Genomics and Biofuels Development

SOURCE:

http://www.nature.com/scitable/topicpage/sequencing-human-genome-the-contributions-of-francis-686

Sequencing Human Genome: the Contributions of Francis Collins and Craig Venter

 

 

By: Jill Adams, Ph.D. (Freelance science writer in Albany, NY) © 2008 Nature Education

 

 

Citation: Adams, J. (2008) Sequencing human genome: the contributions of Francis Collins and Craig Venter. Nature Education 1(1)

 

How did it become possible to sequence the 3 billion base pairs in the human genome? More than a quarter of a century’s worth of work from hundreds of scientists made such projects possible.

 

 

 

 

 

 

Figure 1: Nirenberg’s original notes on the genetic code.

Pieces from Nirenberg’s notebook reveal his notes from the time when his experiments elucidated the genetic code.

Copyright National Human Genome Research Institute.

Before the middle of the twentieth century, the gene was an abstract concept thought to physically resemble a “bead on a string,” and within the scientific community, it was accepted that each gene was associated with a single protein, enzyme, or metabolic disorder. However, this began to change during the 1950s with the birth of modern molecular genetics. In 1952, Alfred Hershey and Martha Chase proved that DNA was themolecule of heredity, and shortly thereafter, Watson, Crick, Franklin, and Wilkins solved the three-dimensional structure ofDNA. By 1959, Jerome Lejeune had demonstrated that Down syndrome was linked to chromosomal abnormalities (Lejeune et al., 1959). Next, the 1961 discovery of mRNA (Jacob & Monod, 1964) and the 1966 cracking of the genetic code (Figure 1; Nirenberg et al., 1966) made it possible to predict proteinsequences based on DNA sequence alone. Nonetheless, although it was well established by this time that DNA was the heredity material and that each nucleus must contain the complete DNA required to instruct the chemical processes of anorganism, the details of reading individual gene sequences, let alone whole genomes, were out of the technical grasp of scientists.

A large part of the reason for this inability to read genesequences was the fact that there were simply very few sequences available to read; furthermore, the tools required to identify, isolate, and manipulate desired stretches of DNA were just evolving. Then, during the late 1960s and early 1970s, the combined work of several groups of researchers culminated in the isolation of proteins from prokaryotes using DNA cut at specific sites and spliced with DNA from other species(Meselson & Yuan, 1968; Jackson et al., 1972; Cohen et al., 1973). With these tools in place, the recombinant DNA age was about to allow scientists to start cloning genes en masse for the first time. Indeed, with the advent of Maxam-Gilbert DNAsequencing in the mid-1970s (Maxam & Gilbert, 1977), it actually became possible to read the entire sequence of a clonedgene, perhaps 1,000 to 30,000 base pairs long, with relative ease.

 

 

Collins and Other Researchers Master Gene Mapping

 

Thanks to these advances, mapping of important disease genes was all the rage by the 1980s, and Francis Collins was one of the masters of this process. Collins made a name for himself by discovering the location of three important disease genes—those responsible for cystic fibrosis, Duchenne muscular dystrophy, and Huntington’s disease. The accomplishments were a result of both cutting-edge cloning techniques like chromosome jumping (Collins et al., 1987; Richards et al., 1988) and plain perseverance. Collins wasn’t the only researcher actively “gene hunting” at this time, however; hundreds of other investigators were also racing to publish detailed descriptions of every new disease gene found.

During the 1980s, the importance of genes was obvious, but determining their location on chromosomes or their sequence of DNA nucleotides was laborious. Early studies of the genome were technically challenging and slow. Reagents were expensive, and the conditions for performing many reactions were temperamental. It therefore took several years to sequence single genes, and most genes were only partially cloned and described. Scientists had already reached the milestone of fully sequencing their first genome—that of the FX174 bacteriophage, whose 5,375 nucleotides had been determined in 1977 (Sanger et al., 1977b)—but this endeavor proved much easier than sequencing the genomes of more complex life forms. Indeed, the prospect of sequencing the 1 million base pairs of the E. coli genome or the 3 billion nucleotides of the humangenome seemed close to impossible. For example, an article published in the New York Times in 1987 noted that only 500 human genes had been sequenced (Kanigel, 1987). At the time, that was thought to be about 1% of the total, and given the pace of discovery, it was believed that complete sequencing of the human genome would take at least 100 years.

In addition to questions about the technical challenges and costs associated with sequencing large genomes, a number of concerns about the scientific basis of these endeavors were also raised. Why spend the time, money, and resources to sequence the whole genome when only a small percentage of it was actually genes? With the huge scale of these projects, there was a logic to prioritizing certain tasks over others—specifically, the target sequencing of coding sequences (genes). Thus, instead of sequencing the raw genome, many researchers sought to study cDNA collections; these are DNA strands that are generated by collecting mRNA from a tissue, then converting it back to complementary DNA. Because cDNA starts as a message in a cell, it represents an actively expressed gene. Moreover, because cells behave differently in different tissues and at different developmental stages, specialized cDNA libraries are valuable tools for assessing what specific genes are at work in a cell at any given time. Scientists could therefore use these libraries to prioritize their sequencing in order to focus on coding sequences first.

At the same time, researchers were also working to identify many more polymorphic genetic markers to use as tools in genemapping. Polymorphisms are the individual DNA base changes that make each of us unique at the level of DNA. The number of known human polymorphisms and microsatellite repeats increased to more than 2,000 by 1992—or 1 per every 2.5 million bases or so (Weissenbach et al., 1992). As researchers characterized more and more polymorphic markers, their chances ofmapping a gene of interest to its chromosomal location increased dramatically.

 

 

Venter Combines Approaches to Make Sequencing Faster and Less Expensive

 

 

 

Figure 2: Growth in nucleotide sequences submitted to GenBank between 1982 and 2005.

The note from each release of GenBank reveal the total number of nucleotides submitted to the database. This graph uses one data point from each year to show the exponential growth rate of nucleotide sequences in this international database. Data from whole genome sequencing is not included in these figures, but expressed sequence tag data and data from sequencing centers is included.

Copyright 2008 Nature Education.

Thus, by the late 1980s, multiple approaches for sequencingDNA were in use, but costs and time constraints were still a limiting factor to research. However, this all began to change with the work of National Institutes of Health (NIH) scientist J. Craig Venter. For several years, Venter had been using automated DNA sequencers to sequence portions of chromosomes associated with Huntington’s disease and myotonic dystrophy (Adams et al., 1991, 1992). Next, Venter tapped collections of cDNA molecules made from brain tissues. Then, in a 1991 paper, he described how he harnessed the power of his high-tech equipment to sequence more than 600 expressed sequence tags (ESTs) from a brain cDNA collection, identifying about half of them as genes, far more than anyone else had ever reported in a single paper to date. Not only did Venter’s paper make an impact, but so did his claims that in his laboratory alone, he could sequence as many as 10,000 ESTs a year at the low cost of $0.12/base. The next year, in a second paper, Venter published the sequences of more than 2,000 genes, although some were incomplete. This brought the total to 2,500 genes sequenced in one laboratory, which was as many as had been sequenced in the entire world to that point (Figure 2).

Many scientists spoke out in criticism of Venter’s brash approach. They noted that by sequencing ESTs, Venter was missing promoter sequences and other sites on DNA that were important for the regulation of gene expression. Furthermore, many critics argued that a focus on cheap volume was no substitute for careful, painstaking science. However, Venter’s speed also spurred other groups—namely, the NIH effort led by James Watson—to step up their efforts to finish the Human Genome Project sooner.

In 1992, Venter left the NIH and, with the help of a venture capitalist, started a nonprofit research institute at which he quickly set up 30 automated sequencers. Venter’s aim in doing so was to complete the sequencing of the human genomefaster than the government-backed (“public”) effort. This competition would later culminate in the simultaneous publication of the draft human genome sequence by both public and private efforts, ahead of schedule and below budget.

The events that occurred from the discovery of DNA’s structure and role as a heredity molecule up through Venter’s high-throughput EST experiments roughly delimit what is now known as the pregenomic era of molecular biology. The molecular tools and methods developed during this era were essential to reaching the milestone of sequencing the entire humangenome.

 

 

References and Recommended Reading

---

Adams, M. D., et al. Complementary DNA sequencing: “Expressed sequence tags” and the Human Genome Project. Science252, 1651–1656 (1991)

———. Sequence identification of 2,375 human brain genes. Nature 355, 632–634 (1992) doi:10.1038/355632a0 (link to article)

Cohen, S. N., et al. Construction of biologically functional bacterial plasmids in vitro. Proceedings of the National Academy of Sciences 70, 3240–3244 (1973)

Collins, F. S., et al. Construction of a general human chromosome jumping library, with application to cystic fibrosis. Science235, 1046–1049 (1987)

Dulbecco, R. A turning point in cancer research: Sequencing the human genome. Science 231, 1055–1056 (1986) doi:10.1126/science.3945817

Jackson, D. A., et al. Biochemical method for inserting new genetic information into DNA of simian virus 40: Circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proceedings of the National Academy of Sciences 69, 2904–2909 (1972)

Jacob, F., & Monod, J. Biochemical and genetic mechanisms of regulation in the bacterial cell. Bulletin de Societe Chimique de France 46, 1499–1532 (1964)

Kanigel, R. The genome project. New York Times, 13 December (1987)

Lejeune, J., et al. Mongolism: A chromosomal disease (trisomy). Bulletin de l’Academie Nationale de Medecine 143, 256–265 (1959)

Maxam, A., & Gilbert, W. A new method of sequencing DNA. Proceedings of the National Academy of Sciences 74, 560–564 (1977)

Meselson, M., & Yuan, R. DNA restriction enzyme from E. coli. Nature 217, 1110–1114 (1968)

Nirenberg, M. W., et al. The RNA code and protein synthesis. Cold Spring Harbor Symposia on Quantitative Biology 31, 11–24 (1966)

Richards, J. E., et al. Chromosome jumping from D4S10 (G8) toward the Huntington disease gene. Proceedings of the National Academy of Sciences 5, 6437–6441 (1988)

Sanger, F., et al. Nucleotide sequence of bacteriophage phi X174 DNA. Nature 265, 687–695 (1977a) (link to article)

Sanger, F., et al. DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences 74, 5463–5467 (1977b)

Weissenbach, J., et al. A second-generation linkage map of the human genome. Nature 359, 794–801 (1992) doi:10.1038/359794a0 (link to article)

Davies, K. Cracking the Genome: Inside the Race to Unlock Human DNA (New York, Free Press, 2001)

SOURCE:

http://www.nature.com/scitable/topicpage/sequencing-human-genome-the-contributions-of-francis-686

Contributors to Genomics recognized by Dan David Prize Awards

http://www.dandavidprize.org/

ERIC LANDER

Laureates 2012 – 2012 Future – Genome Research

Founding Director, Broad Institute Harvard and MIT and director of its Genome Biology Program, Cambridge, MA, USA

Prof. Eric Lander has been a major intellectual force in genomics research. Building on his background in mathematics, he placed genomics on a firm quantitative foundation.

With David Botstein and Phil Green he developed algorithms to allow effective use of polymorphism data for genetic mapping and published the first genetic linkage map of the human genome. As the human genome project got underway, he demonstrated an unusual ability to innovate in the organization of high-throughput methods first in creating genetic maps of the mouse and rat genomes and later as a major contributor to the Human Genome Project.

Lander was a powerful and respected voice in the planning and execution of the genome project. The Center he led contributed much of the data, he pioneered many of the analyses of genome sequence data, and he led in the writing of the landmark publication describing the Human Genome Project first as a draft sequence in Nature, 2001 and later as a full sequence in Nature, 2004. This has become the standard human reference sequence.

Lander has also been at the forefront of applying the genome sequence to the study of human disease, generating the first deep SNP catalogs, applying them to understand the haploid structure of the genome and more recently, championing the use of common variation to the study of complex traits. He has led efforts to understand the functional elements of the human genome, generating genome sequence from multiple other mammals to delineate the conserved elements and to define noncoding RNAs and characterize chromatin states.

Among Prof. Lander’s awards are:  Honorary Degree, Columbia University; Honorary Doctorate, Lund University, Sweden; Honorary Doctorate, University of Massachusetts at Lowell; Gairdner  Foundation International Award, Canada; Max Delbruck Medal, Berlin; Honorary Doctorate, Mount Sinai School of Medicine, New York; Honorary Doctorate, Tel Aviv Universtiy; Millennium Lecturer, The White House; Member of the American Academy of Arts and Sciences; Member of the American Academy of Achievement; and Member of the U.S. National Academy of Sciences.

Beyond his immediate scientific contributions, Eric Lander has attracted talented investigators to the field and fostered their careers. He has also served the community, most recently as co-Chair of the President’s Council of Advisors on Science and Technology.

SOURCE:

http://www.dandavidprize.org/laureates/laureates-2012/130-2012-future/344-eric-lander.html

Eric S. Lander, Ph.D.
By Karen Hopkin

In many ways, Eric Lander’s career has taken as many twists and turns as there are in the helical strands of DNA that he now spends his time trying to decode. Before turning his attention to the human genome, Lander worked as a mathematician, an economist, and even a newspaper reporter, amassing an impressive array of awards and achievements along the way. If the equation that describes Lander’s life story has a common denominator, it would have to be his pursuit of intellectual challenge.

It all began with math. From the start, he was captivated by the power and beauty of numbers. “Math is so elegant. Ideas dovetail perfectly with other ideas to form beautiful intellectual edifices,” he says. What’s more, these mathematical constructions can be used to describe and understand the world around us—making mathematics, to Lander’s mind, the purest product of human thought and “the highest form of crystallized abstraction.”

Lander was a master of mathematics. He placed second in a national math test and h ad the highest grades in his class at Stuyvesant High, one of New York City’s top schools for students who show a talent in math or science. His paper on quasi-perfect numbers—which the 17-year-old Lander proved exist only in theory—won him the Westinghouse Prize. His work at Princeton, where he received his undergraduate degree in mathematics, earned him a Rhodes scholarship at Oxford University. There, Lander completed his graduate degree in pure mathematics. He was well on his way to living his life as a chalk-stained mathematician, but he realized something was missing. “I loved pure mathematics,” says Lander. “But I didn’t want to make it a life.”

“Mathematics is kind of monastic,” he notes. “It’s a very lonely and individual pursuit. And I’m not a very good monk. I like doing things with people.”

This connection with people set into motion the series of happy accidents that would eventually draw Lander into a biology lab. When Lander returned from Oxford, a Princeton professor sent Lander’s résumé to a statistician at Harvard’s School of Public Health, who passed it along to someone at the Business School. Lander was offered a job at Harvard—teaching economics. “I knew no economics whatsoever,” he admits. “But I figured you can learn that stuff.”

Lander was a quick study and a decent teacher, but economics did not provide him with the intellectual stimulation he needed. Fortunately, his little brother did. Arthur Lander, a neuroscientist by training, sent his sibling some papers about mathematical neurobiology. Lander realized that he couldn’t fully understand the research until he learned a bit more about neurobiology. And he couldn’t handle the neurobiology without studying some cell biology, which he couldn’t grasp until he tackled molecular biology. So Lander opted to audit a biology course at Harvard and spent his evenings cloning fruit fly genes in the lab. “I essentially picked up biology on the street corner,” he says with a smile. Of course, in Cambridge—home of Harvard and the Massachusetts Institute of Technology—people who hang out on street corners are just as likely to be discussing biology as anything else.

After a lecture one night, Lander ran into David Botstein, a geneticist at MIT who had developed methods for scanning the genome to find an individual gene that may play a role in disease. He was hoping next to develop a means to untangle the genetics behind more complex human disorders that are thought to arise from subtle disturbances in dozens or hundreds of genes—cancer, diabetes, schizophrenia, even obesity.

The two got to arguing (as good New Yorkers will) about how statistics could be used to search for the genes involved in complex human diseases. Soon, they had the outline of a solution. Lander secured a position as a fellow at the Whitehead Institute for Biomedical Research, where he set to work on the problem. The appointment was a bit unusual—Lander was still a professor at the Harvard Business School—but he made enough progress to receive a MacArthur fellowship for his efforts.

Now a geneticist, Lander joined MIT as a tenured faculty member and a year later he launched the Whitehead Institute/MIT Center for Genome Research, becoming director of one of the first genome sequencing centers in the world. “It was a chaotic career path,” notes Lander. “But everything worked out okay.”

As head of the center, Lander helped build a series of maps that show the basic layout of the human and mouse genomes. In addition to providing the scaffolding needed to assemble the full human genome sequence, completed last year, these maps have proved useful for pinpointing the location of genes involved in disease. For Lander, that’s what his efforts are all about. “Disease is my motivation,” he says. “All the information about one’s risk for disease is hiding in the genome. The goal is to tease out that information.

“A cell already knows what it will be, what it will do,” he adds. “So it’s just a matter of persuading the cell to tell us what it knows.” Lander knows how to be persuasive. Already he and his colleagues at the Whitehead Institute have teased out genes involved in diabetes and gained knowledge that will help scientists diagnose and treat cancers. Whitehead researchers have produced approximately one-third of the human genome sequence. But prying the secrets from the human genome is work that is really just beginning.

The first problem: The human genome is big. Imagine someone dumping 1,000 volumes of the Encyclopaedia Britannica in your living room, says Lander. “How would you tackle all that information? Would you read all the spines first? Or would you start at ‘aardvark’ and go from there?”

But size isn’t the only obstacle. The human genome is also written in code. Scientists are still learning how to decipher the information encrypted in the 3 billion letters that provide the instructions for assembling and operating a human being. The human genome may represent a “book of life,” but it is not yet an open book.

“Looking at the genome is not like looking down at Earth from space and seeing all the clouds and oceans,” says Lander. “You have to think of the questions you want to ask. And then you have to figure out how to ask them.

“That’s my main job,” says Lander. “Thinking about the questions.”

Asking these questions often requires new techniques. And for someone who loves data, who wants answers, the waiting can be the hardest part. “Most days are spent just getting things ready,” says Lander. “So you have to be reasonably good at delayed gratification.” For example, before Lander and his team could build a map of the human genome, they spent months developing new biochemical procedures, new robotics, and new analytical software. “Once everything was in place, making the map was fun.”

Biology may involve a lot of grunt work—certainly more than mathematics does—but Lander doesn’t seem to mind. “The highs, when they come, are better than anything you could imagine.

“Getting to pursue new ideas and new directions, always thinking about new things—it’s intoxicating, it’s addicting,” he says. “I could never give it up.”

SOURCE:

http://www.hhmi.org/biointeractive/genomics/lander.html

J. CRAIG VENTER

Laureates 2012 – 2012 Future – Genome Research

Founder, Chairman, and President of the J. Craig Venter Institute, Rockville, MD and La Jolla, CA, USA and CEO of Synthetic Genomics Inc., La Jolla, CA, USA.

Dr. J. Craig Venter has made numerous contributions to genomics—from ESTs and the first genome of a living species, to the human genome and environmental genomics, to the most recent accomplishments of constructing the first synthetic bacterial cell.

Venter’s initial efforts focused on identifying human genes through random cDNA sequencing (through the use of expressed sequence tags or ESTs) which identified fragments of about half the human genes in his 1995 publication.

Venter led the group that produced the first full sequence of a bacterium, H. influenza, using their whole genome shotgun approach. Five years later, Venter co-founded a company, Celera Genomics, to extend the whole genome shotgun method with newly developed algorithms and instrumentation to sequence the drosophila, human, mouse, rat and mosquito genomes. His group published a draft human sequence simultaneously with the publicly-funded Human Genome Project in 2001.

Venter went on to apply high-throughput sequencing to ocean microbial populations and the human gut, contributing greatly to the rapidly expanding field of metagenomics. More recently, Venter has focused much of his group’s efforts on synthetic genomics, first synthesizing the phix-174 viral genome and transplanting the genome of M. mycoides into a cell of a related species. In 2010 he and the team combined those two technologies, using synthetic oligo-nucleotides to recreate a 1.1 million base pair bacterial genome, and placed it in a new host, thereby constructing the largest synthetically made genome and the first synthetic bacterial cell.

Dr. Venter has received numerous awards and honors including: The 2008 National Medal of Science; Washington, DC, Member, National Academy of Sciences, Washington, DC; Member of the American Society of Microbiology; Honorary Doctor of Science – Syracuse University; the Benjamin Rush Medal – College of William and Mary, VA; Honorary Doctor of Science – Mount Sinai School of Medicine, New York; Scientist of the Year – ARCS Foundation, San Diego; Doctor of Science Honoris Causa – University of Melbourne; Doctorat Honoris Causa – University of Montreal; Doctor of Science Honoris Causa – Imperial College, London; Scripps Institute of Oceanography Nierenberg Prize, La Jolla, CA; Honorary Doctor of Science, Chung Yuan University, Taipei; Presidential Distinguished Scientific Award; World Health Award, Presented by Mikhail Gorbachev, World Awards, Vienna, Austria; University College London Prize in Clinical Science – London, England; Honorary Doctor of Technology, Royal Institute of Technology, Stockholm, Sweden; Medal of the Presidency, Italian Republic, Rimini, Italy; Prince of Asturias Award for Technical and Scientific Research; Fellow, American Academy of Arts and Sciences, Washington, DC; and the Exceptional Service Award for Exploring Genomes.

 SOURCE:

http://www.dandavidprize.org/laureates/laureates-2012/130-2012-future/343-craig-venter.html

DAVID BOTSTEIN

Laureates 2012 – 2012 Future – Genome Research

Anthony B. Evnin Professor of Genomics; Director, Lewis-Sigler Institute for Integrative Genomics; Director, Certificate Program in Quantitative and Computational Biology, Princeton University, Princeton, NJ, USA

Prof. David Botstein has been the intellectual leader of genomics since its inception. He created modern human genetics, championed the Human Genome Project, devised microarrays to exploit genome information for the global assessment of gene expression and has fostered systems biology. He has mentored numerous young scientists in the field, first at MIT, later at Stanford and most recently at Princeton.

Botstein’s 1980 paper “Construction of a Genetic Linkage Map in Man Using Restriction Fragment Length Polymorphisms” was the first to explicitly argue that it would be possible to build a sufficiently dense map of markers through the human genome to permit the mapping of disease genes in families by monitoring the transmission of those markers and disease status through the families. The vision outlined in this paper provided not only the clearest early motivation for the initiation of the human genome project, but its clarity and beauty drew many scientists into the field of genomics.

Following these seminal contributions he has been an intellectual participant in many of the most important key developments in genomics, the most prominent examples of which are: a) the development along with Pat Brown of methods to measure and statistically analyze gene expression profiles and apply these methods to the identification of subtypes of cancer. It would be impossible to overstate the impact of this work both in terms of basic biological research and the direction of thinking about molecular taxonomies of disease;  b) articulation of the need to organize genes into biological groupings to permit systematic pathway analyses, and the initiation of generic systems to do so.   Interestingly, these last areas are clear antecedents of what is now coming to be known as systems biology and which David Botstein is again one of the key intellectual figures.
Among Prof. Botstein’s awards and honors are: Member of the US National Academy of Sciences, the Eli Lilly and Company Award in Microbiology, the Genetics Society of America Medal, the Allen Award of the American Society of Human Genetics, and the Gruber Prize in Genetics.

 

 SOURCE:

 

http://www.dandavidprize.org/laureates/laureates-2012/130-2012-future/342-david-botstein.html

 

MARCUS FELDMAN –

Laureates 2011 – 2011 Past – Evolution

Professor, Department of Biology, Stanford University, Stanford, CA, USA

Prof. Feldman has produced conceptual results of broad interest in the domain of animal and plant evolution. His work has led to highly focused insights of cultural significance such as the out-of-Africa model of human evolution, as well as cultural preferences in different civilizations. His work not only explores basic scientific topics, but investigates the societal consequences of the conclusions he draws in terms of models of evolution.

Prof. Feldman originated the quantitative theory of genetic modifiers of recombination, mutation, and dispersal. His work was the first to show that the pattern of interactions among genes determined whether sex would evolve.

With Cavalli-Sforza, he originated the quantitative theory of cultural evolution. The application of this theory to the culture of son preference in China, and his work on the significance of male/female birth ratio in that country, seems likely to have very important social management consequences, leading to attempts by the Chinese authorities to reduce this preference.

Prof. Feldman demonstrated that today’s world wide pattern of genomic variation is largely due to the sequence of human migrations over the 60,000 years since modern humans left Africa. His finding that about 10 percent of genomic variation is between continents has inspired much of the subsequent discussion on the meaning of race.

Prof. Feldman and collaborators originated “niche construction,” a generalization of evolutionary theory that stresses the feedbacks between organismic evolution and environmental dynamics, demonstrating via his model that phenotypes have a much more active role in evolution than previously thought. This has profoundly influenced subsequent work in evolutionary ecology.

Feldman’s findings have triggered the development of new scientific fields in both the humanities and life sciences. He sheds light on many key issues of evolution, including hominid evolution and the evolution of culture. Feldman has done much demographic work on trends important to humanity’s future.

Among Marcus Feldman’s honors are Elected Fellow, American Association for the Advancement of Science; Elected Member, American Academy of Arts and Sciences; Doctor Pholosophiae Honoris Causa, Hebrew University Jerusalem; Doctor Philosophiae Honoris Causa, Tel Aviv University; member of the editorial boards of various scientific journals; and a member of various international committees and foundations.

SOURCE:

http://www.dandavidprize.org/laureates/laureates-2011/121-2011-evolution/312-marcus-feldman.html

GARY RUVKUN

Laureates 2011 – 2011 Future – Ageing-Facing the Challenge

Professor of Genetics, Department of Molecular Biology, Massachusetts General Hospital, Harvard University

Gary Ruvkun has made a major contribution to the future of human health with the discovery of conserved hormonal signaling pathways with universal influence on animal aging. He is a key figure in defining the genetic basis for human health during aging with his discovery of a core set of hormonal signals and signaling pathways that regulate aging and lifespan in animal models, that are likely to act in humans as well.

In a series of reports starting in the early 1990s Ruvkun defined an insulin signaling pathway that regulates aging in the C. elegans worm and showed that the essential elements of this pathway are conserved in mice and humans. He discovered that like mammals, C. elegans uses an insulin-like signaling pathway to control its metabolism and longevity, suggesting that insulin-like regulation of longevity and metabolism is ancient and universal.

The Ruvkun lab discovered the molecular identity of the many genes in the pathway, including the daf-2insulin receptor, the many insulins that act upstream of the daf-2 receptor, the signal transduction components downstream of the insulin receptor such as age-1, daf-18, pdk-1, akt-1, and akt-2, and the downstream transcription factors daf-16 and daf-3, to reveal the signaling pathway from hormone to membrane receptor to the gene expression changes in the nucleus that regulate metabolism and longevity. Their finding by that the DAF-16/FoxO transcription factor is coupled to insulin signaling via conserved interactions with the kinases AKT and PDK also points to these transcriptional cascades as key in metabolic responses to insulin. This finding has been important for understanding the defects in diabetes as well as for aging research, since the mammalian orthologs of daf-16, the FoxO transcription factors, are regulated by insulin and are emerging now as key outputs of insulin signaling.

Recent insulin signaling mutant analyses in mouse and humans have validated the generality of these discoveries to other animals. Not surprisingly, an insulin-like pathway is now a major theme in animal aging regulation, with many reports of insulin-like regulation of lifespan in Drosophila, mouse, and even human beginning to emerge.

This work had an enormous impact on aging research relevant to longevity and later-life health. These findings catalyzed developments across biogerontology by defining hormone interventions with direct relevance to clinical practice and drug development.

Ruvkun is now using RNAi screens and comparative genomics to reveal the downstream genes regulated by insulin signaling. He discovered a connection between longevity and small RNA pathways, with the production of specific small RNA factors induced in long lived mutant animals.

Among Gary Ruvkun’s awards are: Benjamin Franklin Medal, Franklin Institute; Albert Lasker Award for Basic Medical Research; member of the American Academy of Arts and Sciences; and member of the National Academy of Sciences.

SOURCE:

http://www.dandavidprize.org/laureates/laureates-2011/123-2011-ageing-facing-the-challenge/313-gary-ruvkun.html

ROBERT LANGER

Laureates 2005 – 2005 Future – Materials Science – Tissue Engineering

Robert Langer is the Kenneth L. Germeshausen Professor of Chemical and Biomedical Engineering at the Massachusetts Institute of Technology, USA.

Prof. Langer has pioneered the field of biomaterials and tissue engineering. He has contributed to the development of biocompatible polymers for drug delivery and synthetic polymers to form specific tissue structures creating the field of tissue engineering. His work has allowed the controlled release of macromolecules using biocompatible polymers.

Prof. Langer is also responsible for the creation of numerous novel biomaterials, such as shape memory polymers and materials with switchable surfaces, aerosols and microchips. His work has led to the development of synthetic polymers to deliver cells to form specific tissue structures.

He has been a prolific contributor to this new field of materials science. He has mentored numerous students and post docs who have themselves become leaders in the field.

In 2002 he was awarded the Charles Stark Draper Prize of the NAE. He has won numerous other awards and is one of the few people who have been elected to all three US National Academies (Science, Engineering and Medicine).

SOURCE:

http://www.dandavidprize.org/laureates/laureates-2005/66-2005-future-materials-science/103-prof-robert-langer.html

ROBERT H. WATERSTON

Laureates 2002 – 2002 Future – Life Sciences

Prof. Robert H. Waterston (born 1943 in Michigan, USA) obtained a bachelor’s degree in engineering from Princeton University in 1965 and received both a medical degree and a doctorate in pathology from the University of Chicago in 1972. After a postdoctoral fellowship at the Medical Research Council Laboratory of Molecular Biology in Cambridge, England, Prof. Waterston joined the Washington University faculty in 1976. He is James S. McDonnel Professor of Genetics, head of the Department of Genetics, and director of the School of Medicine’s Genome Sequencing Center, which he founded in 1993. The center was a principal member of the International Human Genome Sequencing Consortium, the public effort to complete the working draft.

He was a recipient of an American Heart Association Established Investigator Award from 1980 to 1985, and held a John Simon Guggenheim Fellowship from 1985 to 1986. He has served as a member of several NIH study sections and as chairman of the NIH’s Molecular Cytology Study Section. He currently serves on the NIH Advisory Council.

Prof. Waterston is a member of Sigma Xi, Alpha Omega Alpha, the Genetics Society and the American Society of Cell Biology. He has published more than 70 peer-reviewed scientific articles.

“It’s powerful information, and the potential benefits are enormous,” Prof. Waterston says. “We all have a responsibility to educate ourselves about the issues. To realize its great promise, scientific information of this sort must be available in an unrestricted form to citizens and scientists everywhere.” 

“For the next hundred years, scientists will use these foundations to make increasingly detailed discoveries about how human beings and other organisms work,” says geneticist Robert H. Waterston of the advances in genetics research. “As a result, more and more will be understood about all aspects of human health, behavior, and disease – and ultimately about therapy and prevention.”

 

 SOURCES:

http://www.dandavidprize.org/laureates/laureates-2002/75-2002-future-life-sciences/121-prof-robert-h-waterston.html

 

JOHN SULSTON

Laureates 2002 – 2002 Future – Life Sciences

subsequently received the Nobel Prize for Medicine in 2002.

Sir John Sulston graduated from Cambridge University in 1963. After completing his Ph.D. on the chemical synthesis of DNA, he moved to the USA to study prebiotic chemistry (the origins of life on Earth). In 1969, Sir John joined Sydney Brenner’s group at the Medical Research Council Laboratory of Molecular Biology in Cambridge where he studied the biology and genetics of the nematode worm, Caenorhabditis elegans. He and his team collaborated with Bob Waterston at Washington University in the USA to sequence the genome of this model organism. In 1992, Sir Sulston was appointed the first Director of the Sanger Centre in Cambridgeshire, which is behind the UK’s contribution to the international Human Genome Project. He stepped down as Director in September 2000.

Sir John Sulston is co-author with Georgina Ferry of The Common Thread: A Story of Science, Politics, Ethics and the Human Genome, to be published by Bantam Press in February 2002. The book tells the story of the sequencing of the human genome from the point of view of one of its leading figures, and discusses what the achievement means for future medical treatments and our understanding of ourselves. In light of the recent ‘gene rush’ by companies to stake claims to parts of the genome, the authors argue that the information it contains should be freely available for the benefit of all, and not carved up for private profit. “The human genome will be the foundation of biology for decades, centuries or millennia to come”.

 

 SOURCE:

http://www.dandavidprize.org/laureates/laureates-2002/75-2002-future-life-sciences/120-prof-john-sulston.html

 

SYDNEY BRENNER

Laureates 2002 – 2002 Future – Life Sciences

subsequently received the Nobel Prize for Medicine in 2002.

Prof. Sydney Brenner’s sustained contributions during the course of a scientific career spanning 40 years are exceptional both in their novelty and in their impact on biology.

During 1957 – 1973, he provided fundamental insights into the genetic code. In 1957, he produced a theoretical paper that presented a formal demonstration of the impossibility of all overlapping codes, insisting that further efforts in deciphering the genetic code be restricted to non-overlapping codes. In 1961 he, together with Francis Crick and others, published evidence for the triphet nature of the genetic code deduced from the frame-shift mutagenesis experiments, which remain a tour de force. He published, together with Fran?ois Jacob and Matthew Meselson, their discovery of messenger RNA, a finding that provided fundamental insights into translation of the genetic code. In 1964 and succeeding years, Prof. Brenner and others published a demonstration of the colinearity of a gene and deciphered nonsense codons by genetics. During the mid-1960s Prof. Brenner, together with Fran?ois Jacob and Fran?ois Cuzin, established the fundamental principles underlying the regulation of DNA replication in E coli. From 1974 to 1990, Prof. Brenner and his colleagues introduced the eukaryotic model C. elegans and demonstrated its utility for studying development. He developed the genetic methodology for dissecting the organism’s developmental program, especially of the nervous system. His students have proved the wisdom of his choice by extending the model to aging and apoptosis. Now that the genome sequence of C. elegans is complete, the usefulness of this system is greatly enhanced. During the 1980s and 1990s, Prof. Brenner made great political and scientific contributions to the establishment of recombinant NDA technology in general and to the human genome project in particular. Among other things, he introduced the study of the putter fish, one of the very few vertebrate organisms to have very little “junk” DNA.

Prof. Sydney Brenner was born in South Africa on 13 January 1927 and studied medicine and science at the University of Witwatersrand, Johannesburg . He went on to Oxford, working in the Physical Chemistry Laboratory, and and receiveed a degree of D.Phil. in 1952. After a brief return to South Africa, he joined the MRC Unit in the Cavendish Laboratory at Cambridge in 1956. He worked here and in its successor, the MRC Laboratory of Molecular Biology at Cambridge, where he was Director from 1979 to 1987. In 1987 he became Director of the MRC Unit of Molecular Genetics, retiring in 1992 from the MRC. He is now Director of the Molecular Sciences Institute, a private research institute in Berkeley, California.

Last year, aged 74, Prof. Brenner accepted an offer to become a research professor at the Salk Institute for Biological Studies. He said: “I don’t want to retire to play golf. Science is one’s hobby and one’s work and one’s pleasure.”

 

 SOURCES:

http://www.dandavidprize.org/laureates/laureates-2002/75-2002-future-life-sciences/119-prof-sydney-brenner.html

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