The most frequently observed form of chromosomal rearrangements is translocation (reciprocal or robertson translocation) that occurence frequency is 1 out 500 newborns. If the group of chromoosmes have all the components within the chromosomes, then it is defined as a balanced structural rearrangements. Some rearrangements are stable and remain unchanged during cell division It is required to have one single centromere and two telomeres for a stable chromosomal reconstruction.
TRANSLOCATION
Translocation is the exchange of pieces of chromosomes between non homologous. Broken pieces are translocating to each other. Translocations are divided into 3 groups:
- Reciprocal Translocation
- Robertsonian Translocation
- Insertional Translocation (Transposition)
Reciprocal Translocation
Two different broken pieces of non homologous chromosomes are exchanging their broken parts reciprocally. It is observed 1 out of 500 at newborns.
Reciprocal translocation mechanism
This type of rearrangement generally does not lead to any phenotypic effect for carriers. However, these individuals carry a high risk (around 85%) due to abnormal gamete formation.
Embryos likely to occur in reciprocal translocation carriers
Centric Fusion Type Translocation (Robertsonian)
This type of translocation occurs between two homologues or non homologues acrocentric chromosomesIn this rearrangement, long and short arms of two different chromosomes fuse to each other. Fused short arms usually disappear and only two long arms joined at the centromere region remain visible. Disappeared fragments of short arms doe not result in any phenotypic effect, because they possess multiple copies of rRNA genes as the acrocentric chromosomes do. 45 chromosomes have been identified in these patients. Although it seems to be numerically abnormal, but no considerable deletion or increment exists in genetic material.
Robertsonian translocation mechanism
As compared to reciprocal translocation, patients with robertsonian translocation show a lower risk of deranged gamete formation with 66% ratio, but it can still be considered as high.
Embryos likely to occur in robertsonian translocation carriers
Insertional Translocation (Transposition)
As one of the two chromosomes undergoes two breaks, the other one has a single break at certain points and the piece resulting from two breaks clings to chromosome where single break occurs. Children of families with insertional translocation problem may encounter duplication or deletion of inserted region due to segregation abnormalities.
Insertional translocation mechanism
DELETION
Deletion is the result of disappearance of a chromosomal segment because of breakage and this type of chromosomal disturbance leads to imbalance. This deletion can take place in two ways. First, a single breakage may either bring about terminal disappearance (terminal deletion) or two fragments may fuse to each other again after broken parts of the chromosome become a part (interstitial deletion). Because broken parts do not generally have centromere, they mostly disappear. If they have centromeres, then they attach to the spindle fibers and do not disappear during cell division. This condition usually does not occur frequently due to its de novo characteristics.
Deletion mechanism
DUPLICATION
Rearrangements of chromosomes include not only deletions of DNA sequences but also duplications of chromosome segments occur. Duplication occurs when one of the two homologous chromosomes undergoes to two breakages and one of which inserts itself onto the other broken part of its homologue. However, duplication is formed mostly in meiosis and one of the chromosomes comprises double copies of certain segments on it.
Duplication mechanism
INVERSION
Two cleavages at two distinct points on a chromosome result in the formation of a chromosome fragment which inverts at its axis and eventually is located on its original position in an inverted pattern. This inversion does not usually cause an abnormal phenotype in carriers because they are in a balanced rearrangement position. There are two types of inversion:
- Paracentric inversion
- Pericentric inversion
Paracentric Inversion
In this type of inversion; one of the short or long arms of a chromosome, excluding the centromere, broken segment inverts and joins itself to its initial position. Since the length of chromosome does not change, it can be identified by banding. Although there is no change in the length of the chromosome, it changes gene order but does not appear in phenotype. Furthermore, individuals with such syndromes generally face with acentric or dicentric recombinant chromosomes in their improper gametes which does not allow to normal birth, though rare incidence has been reported so far. Therefore, it is hardly possible for a carrier to give birth to an alive baby.
Paracentric inversion mechanism
Pericentric Inversion
In this type of inversion; one of the short or long arms of a chromosome, including the centromere, broken segment inverts and joins itself to its initial position. Both length and gene order change. Individuals with this type of disorder produce duplicated or deleted chromosomal segments in their gametes. These segments are the distant parts of inversion. For a carrier, the probability of having a baby with improper karyotyping varies between 1% to 10 % and each pericentric inversion has its own unique risk factor. Because, wide paracentric inversion carriers distal segments are smaller than small pericentric inversion ones, the former carriers can more likely to have alive recombinant children. The most common pericentric inversion, in human, is observed at chromosome 9. Studies have shown no abnormalities at birth, it is considered as polymorphism.
Pericentric inversion mechanism