UNTIL VERY RECENTLY, THE SIZES OF DNA FRAGMENTS THAT COULD BE DEALT WITH BY CLONING AND ELECTROPHORETIC TECHNIQUES WEREGENERALLY ONE TO TWO ORDERS OF MAGNITUDE BELOW THOSE NEEDED FOR A PRACTICAL AND SYSTEMATIC MOLECULAR DESCRIPTION OF HUMAN DNA

UNTIL VERY RECENTLY, THE SIZES OF DNA FRAGMENTS THAT COULD BE DEALT WITH BY CLONING AND ELECTROPHORETIC TECHNIQUES WEREGENERALLY ONE TO TWO ORDERS OF MAGNITUDE BELOW THOSE NEEDED FOR A PRACTICAL AND SYSTEMATIC MOLECULAR DESCRIPTION OF HUMAN DNA RELATIONSHIPS OVER THE RANGE DEALT WITH BY CLASSICAL GENETIC AND CYTOLOGIC ANALYSIS. RECENT DEVELOPMENTS, INCLUDING PULSE FIELD GRADIENT ELECTROPHORESISAND CHROMOSOME HOPPING TECHNIQUES, NOW MAKE IT POSSIBLE TO DEVISE SCHEMES FOR APPROACHES THAT CAN RAPIDLY LOCATE, AT THE MOLECULAR LEVEL, THE ENDS OF LARGE DELETIONS AND TRANS- LOCATIONS. THESE SCHEMES MAY ALSO CROSS DNA LENGTHS OF THE ORDER OF 10 TO 20 CENTI-MORGANS PER STEP TO PROCEED RAPIDLY FROM LOOSELY LINKED DNA MARKERS TO CLOSELY LINKED SEQUENCES OF DIRECT IMPORTANCE FOR FOR GENETIC SCREENING AND ANALYSIS.IN THE PRESENT PHASE I GRANT, ONE SUCH SCHEME FOR A SYSTEMATIC APPROACH IS OUTLINED. THIS SCHEME IS BASED ON SEVERAL STEPS THAT HAVE INDIVIDUALLY BEEN PROVEN PRACTICAL WITHIN THE LAST YEAR AND WHOSE GENERAL USE REQUIRES THE GENERATION OF A SPECIFIC SET OF DNA PROBES. IN PHASE I, GENE LABS WILL DEMONSTRATE THE FEASIBILITY OF NOVEL TECHNIQUES TO RAPIDLY GENERATE THESE PROBES, TOGETHER WITH AN INITIAL DEMONSTRATION OF THEIR UTILITY.