Translocations of chromosome 12. II. A comparison of the distribution of sites of spontaneous and induced breakages.

Human chromosome 12 has been used as a model for studying the distributions of sites of induced and spontaneous breaks. The breakpoints were determined from (1) translocations involving chromosome 12, (2) spontaneous breaks in untreated cultures, (3) radiation-induced breaks, and (4) spontaneous breaks in Fanconi's anaemia. Statistical analysis showed discordance in the results both between the eleven individual bands and between the four assessments. Also, the distribution of breaks for all bands was significantly different from random in each assessment. Certain bands added considerable bias to the results, and when analysed individually, only four bands (p11.1, q13, q24, and p13) showed distributions over the four assessments that were significantly different from random. These four bands are Giemsa-negative bands, and two (p13 and q24) are adjacent to telomeres, while p11.4 is adjacent to the centromere. The fourth band, q13, is a known fragile site. It is concluded that bands adjacent to centromeres, which are not C-banded, are peculiarly sensitive to breakage. Telomeric bands are variable in their response to different conditions of breakage, and both the physical structure of the telomere and the specific gene sequences of individual telomeres are probably of importance in determining this response. The fragile site q13 responds as if breakage at this site is due to the base composition of the DNA.