Abstracts: 



Sequencing 



Technologies 



Advanced Concepts for Base Sequencing in DNA 



J. H. Jett, R. A. Keller, J. C. Martin. E. B. Shera 



Life Sciences Division, Los Alamos National Laboratory, Los Alamos, NM 87545 



(505) 667-3843, FTS 843-3843 



We are addressing the problem of rapidly sequencing the bases in large fragments of 

 DNA. The ideas presented represent the combined effort of a multidisciplinary task 

 force composed of physicists, physical chemists, cellular and molecular biologists, and 

 organic chemists. To reduce mapping requirements, the emphasis is on sequencing 

 methods that are rapid, require little DNA. and are capable of sequencing large 

 fragments. After evaluation of several physical approaches to sequencing, the decision 

 was made to proceed with a modified-tlow-cytometer approach that employs laser- 

 induced fluorescence to detect individual fluorescent molecules. A large fragment of 

 DNA. approximately 40 kb in length, will be labeled with base-identifying tags and 

 suspended in the flow stream of a flow cytometer capable of single molecule detection. 

 The tagged bases will be sequentially cleaved from the single fragment and identified as 

 the liberated tag passes through the laser beam. We are projecting a sequencing rate of 

 100 to 1000 b/s on DNA strands approximately 40 kb in length. 



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