A study of reciprocal translocations and inversions detected by light microscopy with special reference to origin, segregation, and recurrent abnormalities

We analyzed 448 independently ascertained reciprocal translocations and 220 inversions referred to our diagnostic laboratory. Twenty-eight percent of the translocations and 8.5% of the inversions arose de novo, the proportion being influenced by the method of ascertainment. It was highest, 47%, among translocations ascertained through an abnormal phenotype. With the exception of the 3:1 unbalanced segregants, the remainders were equally likely to have been paternally or maternally inherited. The segregation from balanced translocation and inversion carriers showed an equal number of offspring with a normal chromosome constitution and with a balanced rearrangement. The number of unbalanced segregants among the translocations was 2.7% where the proband was balanced, and 19.2% where the proband was unbalanced. There was only a single unbalanced inversion. A search for recurring translocations showed only the well documented t(11;22) to occur with unusual frequency in our series and those of others, and we concluded that the few other translocations that were seen on more than one occasion were likely to be identical by descent (IBD). Similarly the majority of the recurring inversions, with the exception of "common variants," seemed likely to be IBD. However, eight inversions recurred in our data and in most other series and may well be genuine independent rearrangements. A search of the known olfactory receptor (OR) loci and duplicons suggested that such sequences did not form an important contribution to the breakpoints of recurring rearrangements detected by light microscopy. (C) 2003 Wiley-Liss, Inc.