which genetic tests diagnose chromosomal translocations?
Chromosome translocations are a condition in which genetic information located on a certain chromosome is exchanged by a genetic fragment located on another chromosome (in different, non-homologous chromosomes).
This type of mutation is considered the most common chromosome abnormality. According to current research, it appears that one in 600 people carries at least one translocation.
If the translocation causes no change in the amount of chromosome material, this is called a balanced translocation. If the amount of genetic material has decreased or increased due to the exchange and is now unequal (causing extra or missing genes), this is known as an unbalanced translocation. Most translocations occur spontaneously, but people who carry translocations, even ones that have occurred spontaneously, can pass this mutation on to their children.
Robertsonian translocations can only occur in chromosomes with one very long arm and one very short arm – chromosomes 22, 21, 13, 14, and 15 (also known as the acrocentric chromosomes). This condition occurs when one of these chromosomes attaches to another chromosome in the group, creating a new chromosome containing both their genetic material. As a result, a karyotype test will only be able to detect forty-five chromosomes, instead of forty-six.
In most cases of Robertsonian translocation, the short arms are lost during the division, but this condition is not considered harmful since the genetic information located on the short arms is also contained in other areas of the genome and so the carrier will not suffer a loss of important genetic information. However, this may lead to negative consequences for one’s children, since in certain cases children may carry three copies of a certain chromosome.
This type of translocation occurs when people inherit two copies of a certain chromosome from their parents and one of them contains excess genetic information. For instance, if a person inherited one chromosome containing the genetic information of chromosome 21 combined with that of chromosome 14 from one parent, and one copy of chromosome 21 from the same parent, they are at an increased risk for Down syndrome (trisomy 21), since they will also inherit another copy of chromosome 21 from their other parent.
This condition can be prevented by inheriting all copies of a chromosome from one parent (also known as uniparental disomy). However, this condition may also lead to various health impairments.
A reciprocal translocation is a condition in which fragments of two chromosomes exchange locations. The prevalence of this condition in general population is one in every 600 – 900 people. If reciprocal translocations involve important genes, they may cause serious health impairments. This type of translocation usually occurs spontaneously, as opposed to Robertsonian translocations that are hereditary.
The importance of diagnosing translocations
People with balanced translocations can have children who suffer from unbalanced translocations. For instance, a man or woman carrying a balanced translocation have a 10% risk of having a child with a chromosome abnormality detectable via amniocentesis. In addition, balanced translocations increase the risk for recurring miscarriage. Therefore, the diagnosis of balanced translocations in one of the parents is an indication for carrying out preimplantation genetic diagnosis (PGD).
Prenatal diagnosis of chromosome translocations
Amniocentesis is used in prenatal diagnosis of chromosome translocations. When translocations are detected in the fetus, without evidence of translocations in the parents, the risk for intellectual disabilities and other health impairments is around 7-9%. Many of these health impairments can be detected in an ultrasound scan. If an anatomy scan shows no abnormal findings, the risk for other problems is rather low.
Studies that examined babies born with intellectual disabilities without anatomical defects due to a translocation, found that the lack of evidence of anatomical defects in an anatomy scan left the fetus carrying a translocation with a 3-4% risk for intellectual disability, this risk is twice as high as the risk to a fetus without translocations.
To make sure the fetus has no excess genes or missing genes, CGH testing (comparative genomic hybridization, also known as biochip testing) is recommended. If no abnormal findings are detected in this test, the risk decreases to just one percent.