Mapping Instrumentation 



Automated Methods for Large-Scale Physical Mapping 



Tony J. Beugelsdigk and Robert Hollen 



Mechanical and Electronic Engineering Division, Los Alamos National Laboratory. 



Los Alamos. NM 87545 



(505) 667-3169, FTS 843-3169 



The preparation of an ordered-clone collection from human chromosome-specific DNA 

 libraries, necessary for both low- and high-resolution physical maps, offers the next 

 challenge in the task of mapping the entire human genome. This research will focus on 

 instrumenting the front-end processes required in constructing a low -resolution physical 

 map. specifically, the ability to propagate automatically and purify human DNA 

 fragments for subsequent analysis and use. We are assembling the necessary automated 

 hardware designed to manipulate, simultaneously, through numerous preparative steps, 

 a large number of samples containing small volumes (0. 1-0.5 mL), and, finally, to 

 deliver the samples to solid support filters for binding. The samples will automatically 

 be placed on the solid support in a precisely indexed array for multistage analysis and 

 automated data acquisition. 



Based on extensive experience in designing robotic and automated equipment, we 

 anticipate that practical problems in large-scale mapping programs will become evident 

 only after attempts are made to apply new methods to actual map production. For this 

 reason, instrumenting the construction of chromosome-specific physical maps will 

 evolve through a multidisciplinary program. This strategy offers an advantage in that 

 automated devices will become both research and production tools and will be 

 appropriate targets for technology transfer. 



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