A mutation with the change in the position of the chromosome segment is known as translocation. There is no gain or loss of genetic material. Only a segment of a chromosome gets a different position. Reciprocal translocations and non-reciprocal translocations are two main types. A reciprocal translocation involves the exchange of segments between the two chromosomes. Non-reciprocal translocation involves an exchange of segments of the same chromosome or exchange between two chromosomes.
A reciprocal translocation is also known as balanced translocation. It is a condition in which a part of the chromosome has broken off and reattached in another location. This type of translocation increases the risk of recurrent miscarriages. In this type of translocation, the required genetic material is present. However, a piece of a chromosome is merely broken. Later on, it is attached to some other place. It happens mostly during cell division. The genetic material gets exchanged between the non-homologous chromosomes. Balanced translocations can be diagnosed using a karyotype. Unbalanced translocations result into dicentric and acentric chromosomes. Dicentric chromosomes cause lethal double-strand breaks. Acentric chromosomes cause mitotically unstable fragment. The three important events for translocations are two simultaneous double-strand breaks, the juxtaposition of the chromosomes, and unrepaired double-strand breaks.
In the acrocentric chromosomes, breaks occur at or near the centromeric regions leading to translocations known as Robertsonian translocations. The reciprocal exchange of chromosome segments gives rise to one large metacentric chromosome and an extremely small chromosome. The small chromosome gets depleted since it contains very few genes. Thus the person with Robertsonian translocation may possess only 45 chromosomes instead of 46. Though the chromosome number is one less, this type of translocation may not affect the phenotype directly because the acrocentric chromosomes still have all the relevant genes. Also, the genes are present in the variable copy number. The carriers with this type of translocation though have unbalanced gametes, may not possess any phenotypic abnormality. But the risks associated with repeated abortions and miscarriages are very high among them.
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| Image: Balanced (reciprocal) translocations |
Disruption of important genes due to balanced chromosomal rearrangements:
A type of chromosomal aberrations is known as balanced chromosomal rearrangements. Do you know what balanced chromosomal rearrangements are? These types of rearrangements change the chromosomal gene order but do not remove or duplicate any of the DNA. We call these types of aberrations as balanced meaning all the genetic material is still there. However, the genetic material has been exchanged wrongly, thereby leading to disruption of genes.
Case 1: New balanced chromosomal translocations in fetuses:
As per the latest genetic study, fetuses have a new balanced chromosomal aberration. Fetuses with a new type of chromosomal aberrations have a 20% chance of getting these health conditions. About 1 in 2000 pregnant women have a chance that their fetus may develop this type of chromosomal aberration. Moreover, the risk of developing congenital malformations may be high in such cases. However, neurocognitive diseases such as autism and mental retardation may occur in cases of new balanced chromosomal translocations.
A study was conducted by the researchers to find out the number of fetuses with rare chromosomal aberrations. Chorionic villus sampling or amniocentesis was used to diagnose them. Amniotic fluid is collected and analyzed for the abnormalities.
Chorionic villus sampling uses a placental tissue or chorionic villus sample. The chromosomal microarray is used to detect loss or gain of the genetic material. Techniques include FISH and PCR. However, the chromosomal microarray cannot identify the balanced chromosomal translocations. The research strategy involved collecting the blood samples and modern genetic analysis. The results revealed three times higher risk of developing a neurocognitive disorder in those with new chromosomal aberrations.
Case 2: Palindrome Mediated Translocations:
Palindromic sequences consist of two identical sequence units connected with each other in an inverted position. Most of the palindromic repeats are AT-rich. The AT-rich palindromes are present in recurrent and non-recurrent chromosomal translocations. Palindromic sequences are also common in translocations between submetacentric and acrocentric chromosomes. A well-known example is a non-Robertsonian translocation between chromosome 11 and chromosome 22. Human sperm cells revealed such translocations. The carriers of translocation may have infertility problems.
Case 3: Translocation between submetacentric and acrocentric chromosomes:
A submetacentric chromosome is an L-shaped chromosome with unequal arm lengths. An acrocentric chromosome has a very small arm. Studies indicated a balanced translocation between the submetacentric chromosome (number 8) and acrocentric chromosome (number 22). Such types of translocations led to the presence of an extra copy of a chromosome in the child. The condition is known as trisomy results in an extra copy of a chromosome, leading to severe complications such as developmental problems and mild mental retardation. The genome of such an individual may have multiple repetitions of DNA bases or palindromic repeats. Hairpin loops and cruciform structures may be present.
Case 4: X chromosome translocations:
Cytogenetic analysis revealed a new case of X chromosome translocation observed in a three months baby. There was a translocation between the 22nd chromosome and the X chromosome leading to Partial X monosomy and partial trisomy 22.
Case 5: Chromosomal translocations in Leukemias:
Acute leukemia is a type of blood cancer. Acute myeloid leukemia involves cancer of the myeloid cells. The leukemia is progressive and fatal if untreated. There are many examples of translocations in leukemias.
Philadelphia translocation is a common example of a specific translocation in chronic myeloid leukemia (CML) cells. Chromosome 22 specifically shows this type of genetic abnormality. A reciprocal translocation between chromosome 9 and chromosome 22 leads to an unusually short chromosome 22. This type of translocation leads to the fusion of BCR and ABL1 gene. Another example of chromosomal translocation is the acute promyelocytic leukemia. The t(15;17) translocation in promyelocytic leukemia gives rise to the fusion of PML and RARA genes. The retinoic acid receptor gene on chromosome 17 (RARA) gets reciprocally translocated with promyelocytic leukemia (PML) gene on chromosome 15. The PML-RARA gene mutations lead to hybrid proteins.
Some new and non-random type of translocation of chromosomes have been observed and reported on the search engine results. The following are the examples cited from the same. New translocations such as t(9;14), t(14;16), t(8;22) and t(6;8) are found in multiple myelomas. Some more cytogenetic investigations revealed different types of translocations in CLL cells such as translocation between second and eleventh chromosomes. The genes such as MAML2 of chromosome 2 and CXCR4 of chromosome 11 were fused.
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