Sequencing the Human Genome

FIGURE 11.1 Negative ion plasma desorption mass spectrum of the fully protected synthetic hexamer CAACCA. MTr = monomethox-ytrityl, = benzoylcytidine, and R = TBDMS. (Reprinted v ith permission from reference 2). 

FIGURE 11.2 Plasma desorption mass spectra of the unprotected trinucleotides (a) GGT and (b)TTT. (c) Notation used to describe fragmentation. (Reprinted with permission from reference 4). 

FIGURE 11.3 Matrix-assisted UV laser desorption mass spectrum of 40 pmol of the oligode-oxyribonucleotide TTGG (MW = 1204 Da). (Reprinted with permission from reference 5). 

FIGURE 11.4 (a) Structure of the oligonucleotide d(ACTG). (b) Abbreviated notation. 

Most of the approaches that have been proposed for DNA sequencing using MALDI-TOF mass spectrometry have been ladder approaches, recording the molecular ions of a mixture of DNA (or RNA) oligomers. If one considers the masses of the bases (X) and their respective deoxyribonucleotides (dXp) and ribonucleotides (Xp)  

The competition among the private and the public initiatives accelerated the human genome project dramatically. Already in June 2000,5 years ahead of the public prospect and even 1 year in advance of his own proposal, Craig Venter announced the completion of the human genome sequence. One of the most important milestones of genetic research had been achieved. 

Even though German scientists had much influence on the emerging discipline of molecular genetics , the greatest part of the development took place in America and not in Germany. Max Delbrtick, for example, one of the fathers of 

1930 Ph.D. Gottingen, theoretical physics (quantmn mechanics) in the group of Max Born 1930-1932 postdoctoral years in England, Switzerland and Denmark, contact with Wolfgang Pauli and Niels Bohr 1932 Berlin, to work with Otto Hahn and Lise Meitner 

1937 fellowship of the Rockefeller Foimdation to Caltech, work with Emory Ellis 1940 instructor of physics, Vanderbilt University 

1947 Caltech, cooperation with Salvador Limia, establishment of the Phage Group from 1950 work on Phycornyces 

---

Catalyzed by the progress made in sequencing the human genome, the new field of pharmacogenomics offers the promise of being able to make available a host of new rationally designed, safer drugs. 

The National Academy of Sciences il. S.i endorsed a massive national effort to map and sequence the human genome The project target—to produce genetic and physical maps of increasing resolution, with a fully detailed map of the chromosomes—the project to he completed within a decade and ai a cost estimated to be S3 billion,... 

Large-scale and automated DNA sequence determination. Science 254 59-67, 1991. State of the art on the mammoth project to sequence the human genome. 

Sequencing the Human Genome Led to the Discovery of a Large Family of 7TM Bitter Receptors... 

Debating the Issue The race to sequence the human genome took place in both the pubhc and private sectors. Find information about several companies that worked independently on genome research. Is it ethical for them to sell this information, or should it be freely shared ... 

After sequencing the human genome, the most puzzling finding was the small number of protein-encoding genes identified 30.000). Given the... 

F. S. Collins Sequencing the human genome. Ho.spita Practice, January 15,. 35(1997). 

L, Rowen, G. Mahairas, and L. Hood Sequencing the human genome. Science 278, 669 (1997),... 

---