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Title GENE is out of the Bottle, The
Description The 55th Annual Frederick William Reynolds Lecture.
Creator Gesteland, Raymond F.
Publisher University of Utah
Date 1995-11-07
Date Digital 2008-05-29
Type Text
Format image/jpeg
Digitization Specifications Original scanned on Epson Expression 10000XL flatbed scanner and saved as 400 ppi uncompressed tiff. Display images generated in PhotoshopCS and uploaded into CONTENTdm Aquisition Station.
Language eng
Relation Is part of: Annual Frederick William Reynolds lecture
Rights Digital Image Copyright University of Utah
Metadata Cataloger Seungkeol Choe
ARK ark:/87278/s6mk69v5
Setname uu_fwrl
Date Created 2008-07-29
Date Modified 2008-07-29
ID 320758
Reference URL https://collections.lib.utah.edu/ark:/87278/s6mk69v5

Page Metadata

Title Page 8
Description that opened the door to deciphering whole gene sequences. This technology is very elegant and has served science well, but it allows readout of only some 500 bases at a time. With the latest machines that use fluorescent tags for the 4 bases with 48 samples side by side, it would still require some 500,000 machine-days to sequence the 3 billion bases of the human genome once. The cost: $1.00/base with the most efficient groups getting down to $.50. At this cost, to sequence the human genome once equals $1.5 - $3 billion, an amount equal to the whole 15-year budget for the genome project. But five years of this budget is already spent. With the economics in mind, one of the crucial goals for the first five years was to have efficient, cheap technology in place for large-scale sequencing of DNA so that whole genomes could be attacked. This is just where the project has been least successful. Nonetheless, the public data base of DNA sequences is expanding at a geometric rate and currently has a total of a few hundred million bases of sequence from all organisms. But of human DNA, we have only 1 percent of the total of 3 billion bases and most of this is in very short, unconnected fragments of genes. The largest completed chromosomes are from yeast and bacteria, with up to a couple million bases each; the longest stretch from human is about 1 million (human chromosomes range from 50-100 million bases). What is the problem? Why is the cost so high? Why is so little human (and mouse) sequence being generated? One problem is the very serious issue of the front-end loading problem - feeding DNA to be sequenced to the machines. In principle you would think the obvious way to sequence a chromosome would be to start at one end and walk to the other, 500 bases at a time. This is not practical; DNA molecules from chromosomes are too big to handle outside the cell and each step requires results from the previous step. An average human chromosome of 100 million bases requires 200,000 steps and even at a rate of one step per day, it would take forever. So chromosomes must first be broken up into defined pieces (which then are propagated in bacteria using cloning - another key technology to come out of the 1970s) of about 50,000 bases which can be sequenced in parallel. So all large projects to date use a "shotgun" method of sequencing these 50,000-base pieces of DNA. Each piece is further broken up into lots of random fragments and a few thousand of them are chosen at random and sequenced.The computer analyzes the sequences, looking for all the overlaps to assemble the whole. In order to do this with any hope of success, you have to sequence with a 12- to 15-fold redundancy. Thus a very high tax is paid in order to get the sequence to assemble, and even with that investment, assembly often fails. The virtue of the shotgun method
Format image/jpeg
Identifier 008-RNLT-GestelandRE_Page 8.jpg
Source Original Manuscript: The GENE is out of the bottle by Raymond F. Gesteland.
Setname uu_fwrl
Date Created 2008-07-29
Date Modified 2008-07-29
ID 320742
Reference URL https://collections.lib.utah.edu/ark:/87278/s6mk69v5/320742