Translocation (genetics)
Under a translocation (change in location, transfer, from the Latin locus : Place) is understood in the genetics a chromosomal mutation in the chromosome segments have been moved to a different location within the chromosome equivalents (chromosomal). In extreme cases, an entire chromosome can attach to another.
With the exception of the Robertson translocation, which is abbreviated with “rob”, a translocation is abbreviated with “t” in the karyotype .
Forms of translocation
Translocations can be classified according to neutrality, the gain or loss of genome parts (balanced or unbalanced translocations), according to the type of chromosomes involved (reciprocal and Robertson translocations) and according to whether they are germline translocations (principally hereditary) or just somatic translocations (not hereditary) occur.
Balanced translocation
With a balanced translocation ( balanced = in equilibrium) a chromosome or a chromosome segment is translocated to another chromosome, whereby the total amount of the genetic material does not change, but remains in equilibrium. Because of this, a balanced translocation has no phenotypic effects on the person concerned. People with a balanced translocation, however, have an increased probability of producing offspring with an unbalanced translocation (see below), because they also form gametes with an unbalanced translocation. If fertilization takes place between a germ cell with unbalanced translocation and a germ cell in which the genetic material is arranged as usual, the growing child has a translocation trisomy . Pregnant women with a balanced translocation are at increased risk of losing their unborn child to a miscarriage . A balanced translocation can also be of clinical importance in the development of cancer. In acute myeloid leukemia (AML) there is a balanced translocation in hematopoietic progenitor cells in about 20% of cases. Fusion genes can arise that play a role in activating the genes that are important for proliferation and differentiation.
The karyotype in the presence of a balanced translocation can e.g. E.g. 45, XX, t (14; 21) or 45, XY, t (14; 21) (if a whole chromosome is translocated) or 46, XX, t (14; 21) or 46, XY , t (14; 21) (if only part of the chromosome is translocated).
Unbalanced translocation
An unbalanced translocation is characterized by a quantitative change in the genome, which is caused by the fact that genetic material is lost or is present in addition to the genetically present. An example of this form of translocation is the translocation trisomy 21 , in which additional genetic material from the 21st chromosome has accumulated on another chromosome. The karyotype of a translocation trisomy 21 can e.g. B. are: 46, XX + 21, t (14; 21) or 46, XY + 21, t (14; 21) / translocation trisomy 21/14.
Reciprocal translocation
In the case of a reciprocal translocation ( Latin reciprocus : reciprocal, mutual), an exchange of pieces between non- homologous chromosomes has taken place. Here, too, the amount of genes remains in balance. It is important to note that what matters here is the segregation of the chromosomes into the gametes: Let's call the “normal” chromosomes N1 and N2, the “translocated” T1 and T2. In the so-called adjacent - 1 segregation, N1 + T2 and N2 + T1 come together. This combination is mostly fatal. The other option is alternate segregation, N1 + N2 and T1 + T2, which combination produces two complete gametes and is viable. This whole process produces gametes in a 1: 1 ratio. Half of the gametes are not viable, which is known as semi-sterility.
Robertson Translocation (Centric Fusion)
The Robertson translocation (also Robertsonian translocation or derivative chromosome , abbreviated to “rob” or “der” in the karyogram ) is a special form of translocation that only occurs between the acrocentric chromosomes (centromere at the end, the shorter arm very small ; in humans chromosomes 13 , 14 , 15 , 21 , 22 and the Y chromosome ). It is particularly common between chromosomes 13 and 14 . It was first described by WRB Robertson in 1916 and named after him because of that. It arises from the relocation of a comparatively large chromosome section to a non-homologous chromosome: Two acrocentric chromosomes (chromosomes whose constrictions are near the chromosome ends) combine to form a metacentric chromosome (chromosome whose constriction is in the middle). This happens through a fusion (connection, merging) of two long arms of acrocentric chromosomes in the centromer area (= in the area of the constriction where the spindle fibers attach during division), whereby the two short arms are lost (see deletion ) and thus a metacentric one Chromosome is created.
A Robertson translocation can be balanced or unbalanced. People with a balanced Robertson translocation have the usual phenotype. In the representation in the karyogram, however , their genotype is noticeable because 45 chromosomes can be detected instead of the usual 46. Although they can produce offspring with a similarly normal phenotype, gametes with quantitatively and qualitatively changed chromosome sets occur during germ cell formation: The fused chromosome or a missing chromosome or an extra long arm of the acrocentric chromosome can be passed on to the offspring become. The karyotype in the presence of a balanced Robertson translocation can e.g. E.g. 45, XX, rob (14; 21) or 45, XY, rob (14; 21), the karyotype in the presence of an unbalanced Robertson translocation z. E.g .: 46, XX + 21, rob (14; 21) or 46, XY + 21, rob (14; 21). In the latter, the person concerned has Down syndrome with Robertson's translocation 21/14 (translocation trisomy 21).
This form of translocation can be detected in humans with the acrocentric chromosomes of the numbers 13, 14, 15, 21 and 22, in which the centromere is close to the end (in contrast to metacentric chromosomes, in which the centromere is located quite centrally) . The loss of the short arms when the two long arms are fused is not particularly significant in acrocentric chromosomes, since the short arms do not contain any relevant genes . In mice we know for some time to the frequent occurrence of Robertson translocations. 124 of the possible 171 forms of the Robertson translocation are known.
Somatic translocations
The so-called Philadelphia chromosome is characterized by a reciprocal translocation t (9:22) caused by a transfer (transfer, from Latin transferre : transferred) of the main part of the long arm from chromosome 9 to chromosome 22 . As a result of this translocation, the Abl gene for the tyrosine kinase ABL1 (a proto-oncogene ) on chromosome 9 comes under the control of the promoter from the "breakpoint cluster region" (Bcr) on chromosome 22 and the fusion gene Bcr-Abl is created . This leads to the activation of the proto-oncogene to the oncogene through the expression of a constitutively active Abl tyrosine kinase . A Philadelphia chromosome occurs in over 95% of people with chronic myeloid leukemia and in 5% of all children and 20 to 30% of all adults with acute lymphoblastic leukemia .
In Burkitt's lymphoma , a reciprocal translocation between chromosomes 8 and 14 is often observed (t (8:14)), in mantle cell lymphoma a reciprocal translocation between chromosomes 11 and 14 (t (11:14)).
Examples from evolution
By comparing the great apes ( chimpanzees , gorillas and orangutans , each with 48 chromosomes), a gorilla-specific translocation could be localized. The reconstruction results in the original karyotype of the group with 48 chromosomes, as it is still present in chimpanzees and orangutans today. The affected chromosomes correspond to chromosomes 5 and 17 of humans , who with only 46 chromosomes also belong to the superfamily of humans (hominoidea).
See also
Web links
Individual evidence
- ^ Griffith, Wessler, Lewontin, Gelbart, Suzuki, Miller: Introduction to genetic analysis, Eight Edition
- ↑ WSLH: Basic Nomenclature For Cytogenetics ( Memento from August 6, 2013 in the Internet Archive )
- ↑ Sander, Marie-Sandrine: Incidence of secondary chromosomal aberrations in mantle cell lymphoma (MCL) with translocation t (11; 14) (q13; q32)
- ^ A. Jauch, J. Wienberg, R. Stanyon, N. Arnold, S. Tofanelli, T. Ishida, T. Cremer: Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting. In: Proceedings of the National Academy of Sciences . tape 89 , no. 18 , September 15, 1992, pp. 8611–8615 , doi : 10.1073 / pnas.89.18.8611 ( PDF ).