DNA Sequencing and the Human Genome Project hIstory oTechnology ° Analysis
DNA Sequencing and the Human Genome Project •History •Technology •Analysis
History Timeline 1953 James watson and francis Crick discover the double helical structure of DNA( Nature 1972 Paul berg and co-workers create the first recombinant DNA molecule (PNAS 1977 Allan Maxam and Walter Gilbert(pictured) at Harvard University and Frederick Sanger at the U.K. Medical Research Council (MRC) independently develop methods for sequencing DNA(PNA February: PNAS, December)
History • Timeline – 1953 James Watson and Francis Crick discover the double helical structure of DNA ( Nature ). – 1972 Paul Berg and co-workers create the first recombinant DNA molecule ( PNAS ). – 1977 Allan Maxam and Walter Gilbert (pictured) at Harvard University and Frederick Sanger at the U.K. Medical Research Council (MRC) independently develop methods for sequencing DNA ( PNAS , February; PNAS , December)
History(cont'd) 1980 David Botstein of the Massachusetts Institute of Technology, Ronald Davis of Stanford University, and Mark Skolnick and Ray White of the University of Utah propose a method to map the entire human genome based on RFLPs(American ournal of Human Genetics 1984 Charles Cantor and David Schwartz of Columbia Univers ity develop pulsed field electrophoresis MRC SCientists decipher the complete DNA sequence of the Epstein-Barr virus, 170 kb 1985 Kary Mullis and colleagues at Cetus Corp. develop PCR, a technique to replicate vast amounts of dNa 1986 Sydney Brenner, DOE, Renato Dulbecco, CSH Symposium all publicly advocate a human genome project. Not everyone convinced!
History (cont’d) – 1980 David Botstein of the Massachusetts Institute of Technology, Ronald Davis of Stanford University, and Mark Skolnick and Ray White of the University of Utah propose a method to map the entire human genome based on RFLPs (American Journal of Human Genetics ). – 1984 Charles Cantor and David Schwartz of Columbia University develop pulsed field electrophoresis MRC scientists decipher the complete DNA sequence of the Epstein-Barr virus, 170 kb – 1985 Kary Mullis and colleagues at Cetus Corp. develop PCR , a technique to replicate vast amounts of DNA – 1986 Sydney Brenner, DOE, Renato Dulbecco, CSH Symposium all publicly advocate a human genome project. Not everyone convinced!
History(cont'd) 1986 Leroy Hood and Lloyd Smith of the California Institute of Technology and colleagues announce the first automated DNA Sequencing machine 1987 An advisory panel suggests that DOE should spend $l billion on mapping and sequencing the human genome over the next 7 years and that DOE should lead the U.S. effort. DOE's Human Genome Initiative begins David Burke, Maynard Olson, and George Carle of Washington University in St. Louis develop YACs(left) for cloning, increasing DuPont scientists develop a system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides(Marv Caruthers in Biochem, one of the patent holders) Applied Biosystems Inc, puts the first automated se based on Hoods technology on the market
History (cont’d) – 1986 Leroy Hood and Lloyd Smith of the California Institute of Technology and colleagues announce the first automated DNA sequencing machine – 1987 An advisory panel suggests that DOE should spend $1 billion on mapping and sequencing the human genome over the next 7 yearsand that DOE should lead the U.S. effort. DOE's Human Genome Initiative begins. David Burke ,Maynard Olson , and George Carle of Washington University in St. Louis develop YACs (left) for cloning, increasing insert size 10-fold DuPont scientists develop a system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides (Marv Caruthers, in Biochem, one of the patent holders) Applied Biosystems Inc. puts the first automated sequencing machine, based on Hood's technology, on the market
History(cont'd) 1988 NIH establishes the Office of Human Genome Research and snags Watson (pictured) as its head. Watson declares that 3%o of the genome budget should be devoted to studies of social and ethical issues -1989 Olson, Hood, Botstein, and Cantor outline a new mapping strategy, using STS DOE and Nih start a joint committee on the ethical, legal, and social implications of the HGP NIH office is elevated to the National Center for Human Genome research (NCHGR), with grant-awarding authority
History (cont’d) – 1988 NIH establishes the Office of Human Genome Research and snags Watson (pictured) as its head. Watson declares that 3% of the genome budget should be devoted to studies of social and ethical issues. – 1989 Olson ,Hood ,Botstein , and Cantor outline a new mapping strategy, using STSs. DOE and NIH start a joint committee on the ethical, legal, and social implications of the HGP. NIH office is elevated to the National Center for Human Genome Research (NCHGR), with grant-awarding authority
History(cont'd) 1990 NIH and DOE publish a 5-year plan. Goals include a complete genetic map, a physical map with markers every 100 kb, and sequencing of an aggregate of 20 Mb of DNA in model organisms by NIH and DOE restart the clock, declaring I October the official beginning of the HGP Cost per base David Lipman, Eugene Myers(CU CS Department! ) and colleagues at the National Center for Biotechnology Information(NCBD publish the BLAST algorithm for aligning sequences 1991 NIH biologist J. Craig Venter announces a strategy to find expressed genes, using ESTS (Science ) A fight erupts at a congressional hearing I month later, when Venter reveals is filing patent applications on thousands of these partial genes
History (cont’d) – 1990 NIH and DOE publish a 5-year plan. Goals include a complete genetic map, a physical map with markers every 100 kb, and sequencing of an aggregate of 20 Mb of DNA in model organisms by 2005 NIH and DOE restart the clock, declaring 1 October the official beginning of the HGP. Cost per base ~$0.75 David Lipman, Eugene Myers (CU CS Department!), and colleagues at the National Center for Biotechnology Information (NCBI) publish the BLAST algorithm for aligning sequences – 1991 NIH biologist J. Craig Venter announces a strategy to find expressed genes, using ESTs (Science ). A fight erupts at a congressional hearing 1 month later, when Venter reveals that NIH is filing patent applications on thousands of these partial genes
History(cont'd) 1992 Watson resigns as head of NCHGR Venter leaves NIH to set up The Institute for Genomic Research(TIGR) William Haseltine heads its sister company, Human Genome Sciences to commercialize TIGR products Britain's Wellcome Trust enters the HGP with $95 million Mel Simon of Caltech and colleagues develop BACs for cloning U.S. and French teams complete the first physical maps of chromosomes David Page of the Whitehead Institute and colleagues map the chromosome, Daniel Cohen of the Centre d'Etude du Polymorphisme Humain(CEPH and Genethon and colleagues map chromosome 21 U.S. and French teams complete genetic maps of mouse and human; mouse average marker spacing 4.3 CM, Eric Lander and colleagues at Whitehead, human, average marker spacing 5 cM, Jean Weissenbach and colleagues at CEPH
History (cont’d) – 1992 Watson resigns as head of NCHGR Venter leaves NIH to set up The Institute for Genomic Research (TIGR), William Haseltine heads its sister company, Human Genome Sciences, to commercialize TIGR products. Britain's Wellcome Trust enters the HGP with $95 million Mel Simon of Caltech and colleagues develop BACs for cloning U.S. and French teams complete the first physical maps of chromosomes: David Page of the Whitehead Institute and colleagues map the Y chromosome; Daniel Cohen of the Centre d'Etude du Polymorphisme Humain (CEPH) and Généthon and colleagues map chromosome 21 U.S. and French teams complete genetic maps of mouse and human: mouse, average marker spacing 4.3 cM , Eric Lander and colleagues at Whitehead; human, average marker spacing 5 cM, Jean Weissenbach and colleagues at CEPH
History(cont'd) 1993 Francis Collins of the University of Michigan is named director of HGR NIH and Doe publish a revised plan for 1993-98. The goals include sequencing 80 Mb of dna by the end of 1998 and completing the human genome by 2005. Cost per base target $0. 10/base finished The Wellcome Trust and MRC open the Sanger Centre at Hinxton Hall, south of Cambridge, U.K. Led by John Sulston The GenBank database officially moves from Los Alamos to NCBI ending NIH's and DOE's tussle over control 1994 Jeffrey Murray of the University of lowa, Cohen of Genethon, and colleagues publish a complete genetic linkage map of the human genome, with an average marker spacing of0.7 CM
History (cont’d) – 1993 Francis Collins of the University of Michigan is named director of NCHGR. NIH and DOE publish a revised plan for 1993-98. The goals include sequencing 80 Mb of DNA by the end of 1998 and completing the human genome by 2005. Cost per base target $0.10/base finished. The Wellcome Trust and MRC open the Sanger Centre at Hinxton Hall, south of Cambridge, U.K. Led by John Sulston The GenBank database officially moves from Los Alamos to NCBI, ending NIH's and DOE's tussle over control – 1994 Jeffrey Murray of the University of Iowa, Cohen of Généthon, and colleagues publish a complete genetic linkage map of the human genome, with an average marker spacing of 0.7 cM
History(cont'd) 1995 Venter and Claire Fraser of TIGR and Hamilton Smith of Johns Hopkins publish the first sequence of a free-living organism, Haemophilus influenzae Patrick Brown of Stanford and colleagues publish first paper using a printed glass microarray of complementary DNA(CDNA) probe Researchers at Whitehead and Genethon(led by Lander and Thomas Hudson at Whitehead) publish a physical map of the human genome containing 15,000 markers 1996 NIH funds six groups to attempt large-scale sequencing of the human genome Affymetrix makes Dna chips commercially available An international consortium publicly releases the complete genome sequence of the yeast cerevisiae
History (cont’d) – 1995 Venter and Claire Fraser of TIGR and Hamilton Smith of Johns Hopkins publish the first sequence of a free-living organism, Haemophilus influenzae , 1.8 Mb Patrick Brown of Stanford and colleagues publish first paper using a printed glass microarray of complementary DNA (cDNA) probe Researchers at Whitehead and Généthon (led by Lander and Thomas Hudson at Whitehead) publish a physical map of the human genome containing 15,000 markers – 1996 NIH funds six groups to attempt large-scale sequencing of the human genome. Affymetrix makes DNA chips commercially available. An international consortium publicly releases the complete genome sequence of the yeast S. cerevisiae
History(cont'd) 1997 Fred Blattner Guy Plunkett, and University of Wisconsin, Madison, colleagues complete the DNA sequence of E coli, 5 Mb 1998 NIH announces a new project to find SNPS Phil Green(pictured) and Brent Ewing of Washington University and colleagues publish a program called phred for automatically interpreting sequencer data. Both phred and its sister program phrap(used for assembling sequences) had been in wide use since 1995 PE Biosystems Inc. introduces the PE Prism 3700 capillary sequencing machine Venter announces a new company named celera and declares that it will sequence the human genome within 3 years for $300 million In response, the Wellcome Trust doubles its support for the HGP to $330 million taking on responsibility for one-third of the sequencing
History (cont’d) – 1997 Fred Blattner ,Guy Plunkett , and University of Wisconsin, Madison, colleagues complete the DNA sequence of E. coli , 5 Mb – 1998 NIH announces a new project to find SNPs Phil Green (pictured) and Brent Ewing of Washington University and colleagues publish a program called phred for automatically interpreting sequencer data. Both phred and its sister program phrap (used for assembling sequences) had been in wide use since 1995. PE Biosystems Inc. introduces the PE Prism 3700 capillary sequencing machine Venter announces a new company named Celera and declares that it will sequence the human genome within 3 years for $300 million In response, the Wellcome Trust doubles its support for the HGP to $330 million, taking on responsibility for one-third of the sequencing
