HERITABLE FRAGILE SITES ON HUMAN-CHROMOSOMES .11. FACTORS AFFECTING EXPRESSION OF FRAGILE SITES AT 10Q25, 16Q22, AND 17P12

Abstract

The fragile sites at 10q25, 16q22 and 17p12 can be induced in lymphocyte culture by BrdU [bromodeoxyuridine] or BrdC [bromodeoxycytidine] added 6-12 h prior to harvest. Without induction, fra(10)(q25) is rarely expressed spontaneously, whereas fra(16)(q22) is frequently expressed spontaneously. Fra(17)(p12) is frequently expressed spontaneously but is probably expressed only after induction in some individuals. Distamycin A, netropsin and Hoechst 33258 induced high levels of expression of fra(16)(q22) and fra(17)(p12) but did not enhance expression of fra(10)(q25). The mechanisms of induction of fra(16)(q22) by BrdU and distamycin A appear to be different, since the time of induction by BrdU reaches a maximum about 12 h prior to harvest whereas induction by distamycin A requires much longer exposure. The fragile sites at 10q25 and 16q22 were both induced in fibroblast culture by BrdU. Fra(17)(p12) is accepted as a fragile site because preliminary studies show that it behaves similarly in lymphocyte culture to fra(16)(q22); however, there is only limited evidence for fragility at 17p12.