Chromosomal translocations are a result of chromosomal instability and are caused by rearrangements in genetic information, usually between two chromosomes. Chromosomal instability occurs after exposition of an individual to clastogenes (=substances, that cause chromosomal breaks) or due to malfunction of reparation mechanisms. Critical lesions, which leads to chromosomal breaks, are double strand DNA breaks. Consequences of these deviations depend on the fact, whether a normal amount of genetic information is maintained. An alteration in the amount of genetic information leads to phenotypic manifestations. The severity of the phenotype corresponds to the size of the genome that was lost or is present in a bigger amounts.
Translocations can be
- balanced (= the amount of the genetic information within the cell is maintained. Balanced translocation do not necessarily have to affect the phenotype of their host, but their rate is significantly increased in the group of mentally retarded people and they often cause sterility)
- unbalanced (= the original amount of DNA is altered)
- intrachromosomal (= within one chromosome)
- interchromosomal (= between two chromosomes)
- reciprocal (non-Robertsonian)
- Robertsonian translocations
- Translocations between more than two chromosomes are called complex translocations
Are exchanges of genetic material between two non-homologous chromosomes. The number of chromosomes within the cell stays the same. Translocations can cause formations of chimeric proteins, i.e. translocation between chromosome 9 and 22 in humans (t 9;22). This translocation leads to the formation of a Philadelphia chromosome, which is typically present in leukemia. Chromosome 9 carries a protooncogene ABL and chromosome 22 carries a BCR gene, after translocation a fusion protein ABL/BCL is created which causes malignant transformation.