Cartographic study: breakpoints in 1574 families carrying human reciprocal translocations

Reciprocal translocations (rcp) are among the most common constitutional chromosomal aberrations in man. Using a European database of 1574 families carrying autosomal rcp, a cartographic study was done on the breakpoints involved. The breakpoints are non-randomly distributed along the different chromosomes, indicating "hot spots". Breakpoints of rcp that result in descendants that are unbalanced chromosomally at birth are more frequent in a distal position on chromosomal arms, and 65% of them are localised in R-bands. Among the R-bands, bands rich in GC islands and poor in Alu repetitive sequences are more frequently the site of breakpoints, as well as bands that include a fragile site. This result suggests that the variation in degree of methylation in GC islands could be involved in chromosomal breakage and hence in chromosomal rearrangements. The heterogeneity of the human chromosomal structure has been demonstrable by metaphase banding techniques since 1970. In contrast to G-bands, R-bands are sites of high gene concentration (Korenberg et al. 1978), are relatively rich in cytosine plus guanine (GC), and in Alu repetitive DNA sequences (Korenberg and Rykowski 1988). More recently Holmquist (1992) has proposed four types of R-bands, depending on their relative richness in GC and Alu DNA sequences. R-bands rich in GC correspond almost exactly to T-bands (Dutrillaux 1977). They contain 65% of all genes while they represent only 15% of the genome (Holmquist 1992). The aim of this study is to analyse the distribution of the breakpoints along chromosomes from a European database of autosomal rcp in order to relate it to the specificity of different chromosomal regions.