Parental origin and mechanism of formation of X chromosome structural abnormalities: Four cases determined with RFLPs

Parental origin and mechanism of formation of X chromosome structural anbormalities were studied in one each case of dup(X)(pter→ p11.4::p22.1→qter), del(X)(qter→p11:), i(X)(qter→cen→qter), and inv dup(X) (pter→q22::q22→pter) using various X-linked RFLPs as genetic markers. Segregation and densitometric analyses on polymorphic DNAs revealed that the dup(Xp) and the del(Xp) are both of paternal origin and the i(Xq) and i dic(X) are of maternal origin. The dup(Xp) had arisen by an unequal sister chromatid exchange and the del(Xp) had occurred through an intrachromosomal breakage-reunion mechanism, both in the paternal X chromosome. The i(Xq) had arisen either through centromere fission of a maternal X chromosome, followed by duplication, of its long-arm, or through a translocation between two maternal X chromosomes after meiotic crossing-over. The inv dup(X) arose through sister chromatid breakage and reunion in a maternal X chromosome. These results, together with those of previous studies, suggest that the de novo abnormalities due to events involving centromere disruption arise predominantly during oogenesis, while those due to simple breakage-reunion events occur preferentially during spermatogenesis.