Translocations are the most frequent chromosome structural aberration in the human population, yet little is known about their aetiology. Here, factors that might influence the occurrence of constitutional translocations in the population are examined. By analysing >10000 translocations from two large databases of cytogenetic abnormalities, chromosome size is identified as the major determinant of translocation frequency. This probably reflects the large target size for double-strand breakage and repair presented by the largest chromosomes. There is also evidence for selection against translocations that involve breakage through the most gene-dense chromosomes. Lastly, it is suggested that nuclear organization of chromosomes impinges on the frequency of translocations amongst the smallest autosomes.
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