The ordering of DNA clones has been initiated for clironiosomes 5, II, 16, 17, 19,21, 

 22. and X. Efficacy and speed have been demonstrated in these projects for three 

 distinct ordering strategies. 



The 1988 identification of the basic repeat sequence of the human telomere at 



LANL has been followed by the cloning of telomeric regions of several chromosomes. 

 Thus the "end points" of the physical mapping tasks are becoming well defined and are 

 providing orientation for mapping activities. The telomeric sequence has been found to 

 be conserved across vertebrate species. 



Novel computer software now makes possible the direct entry of raw experimental 

 results into a database, subsequent data analysis, and future transmission of results to 

 other laboratories and data repositories. The.se systems are simplifying the requirements 

 for recording and processing map and sequence data. 



Broader problems in the area of human genome Informatics have been addressed in 

 a series of workshops cosponsored by concerned federal agencies. To pursue these 

 issues further, the Joint Infomiatics Task Force (JITF) has now been formed. Recently, 

 guidelines have been published to eliminate ambiguities in clone names and thus 

 provide for unique naming or identification. 



Very fast computer boards for sequence search and comparison tasks have been 

 demonstrated and are being commercialized. 



Improvements in protocols for construction of yeast artificial chromosomes 



(YACs) have culminated with the production of YAC libraries whose human DNA 

 inserts have an average size of 410,000 bp. 



For chromosome mapping through pulsed-field gel electrophoresis, the number of 

 useful cleavage sites has been increased by protocols for modifying DNAs in vitro. 



The reliability of a core DNA-sequencing step of the Sanger strategy has been 

 substantially increased, through genetic engineering of DNA polymerase (of 

 bacteriophage T7) and modification of polymerase reaction conditions. 



A scheme for rational combination of random and directed-sequencing runs on 



cosmids provides for much more economical use of expensive primers. 



The processing of DNA fragment autoradiographs into assembled sequence data is 

 now being accelerated by automatic film readers coupled with computerized analysis. 



A novel scheme for sequencing by hybridization (SBH) crucially depends on a 

 capacity to distinguish short segments of perfectly base-paired DNA from segments 

 with even a single base-pair mismatch. Both the effective theory and practice for such 

 discrimination have now been demonstrated. 



27 



