Research Facility 

 Narratives: LANL 



In the National Laboratory Gene Library Project, libraries using the vector Charon 40 

 and cosmid libraries using the vector sCos 1 have been constructed for human 

 chromosomes 16, 5, 8, and 4. A lambda library has been made for the X chromosome. 



Progress has been made in the detection of single fluorescent molecules in a flowing 

 liquid — an essential step in LANL's proposed system for sequencing single DNA 

 molecules at a rate of -10' bp/s. In this approach, the molecule is excited by a laser. 

 LANL has markedly enhanced the signal-to-noise ratio so that single molecules such as 

 fluorescein may be detected reliably. 



A physical mapping database pilot project has been designed and is being used to 

 manage data accumulating in the physical mapping project at LANL. A relational 

 database has been established and is being managed with the Sybase data management 

 system. Every clone is given a unique identifier and an arbitrary number of charac- 

 teristics such as source, restriction fragments derived by various digests, restriction 

 map, probe hybridization, relation to other clones, and relation to genetic markers or 

 sequences. 



A process has been established for identifying industrial partners. A workshop, attended 

 by 24 companies, was held at Los Alamos, and proposals from 8 of those companies 

 that responded to a request for proposal (RFP) are now under review. 



Future Directions 



• Establish, jointly with Lawrence Livermore National Laboratory (LLNL), a 

 resource to make available arrayed libraries of cosmid clones for all the human 

 chromosomes. The generation of YAC libraries from flow-sorted material will be 

 investigated. 



• Continue physical mapping of chromosome 16 with cosmid clones. Strategies and 

 techniques for linking cosmid contigs will be developed, mostly with YAC clones; 

 mapping of additional chromosomes will be initiated. Clones will be distributed to 

 provide ties between physical and genetic linkage maps. 



• Establish an integrated pilot program for sequencing of megabase regions generated 

 by physical mapping. 



• Develop a system for sequencing single DNA molecules at a rate of -10' bp/s. 



• Develop computational tools to support the Library Resource, clone characterization 

 for physical mapping, and assembly of the physical map from clone overlap 

 probabilities. 



• Develop an integrated database for physical mapping and sequence information 

 (linked to the genetic mapping database) plus computation, communication, and 

 analysis tools to make them accessible at scientific workstations in molecular 

 biology laboratories. 



44 



