Translocations in the germline

Our DNA is stored on $46$‍ discrete chromosomes, with one set of $23$‍ from each parent. During prophase of meiosis I these homologous chromosomes line up and exchange information during the process known as crossing over. However, if the chromosomes misalign, the resulting gametes may be unequal in chromosome content and, therefore, nonviable. Chromosomal rearrangements known as translocations are one major source of misalignment. Translocations can be classified into two main categories: reciprocal and nonreciprocal.

During a reciprocal translocation, two chromosomes (often non-homologous) exchange genetic information. In the majority of reciprocal translocations, the chromosome number does not change. As many as $1$‍ in $600$‍ newborns have a reciprocal translocation somewhere in their genome. While this may have no direct effect on the health of the individual carrying the translocation, it may lead to infertility and / or miscarriage. When chromosomes containing a translocation try to align during meiosis, non-homologous chromosomes may end up pairing with each other. This can lead to unequal segregation of chromosomes and eventually cause spontaneous abortion of the fetus.

Robertsonian translocations are reciprocal translocations that involve acrocentric chromosomes. These are chromosomes in which the centromere is almost entirely at one end. During the translocation, the longer (q) arms of two acrocentric chromosomes fuse to create one larger chromosome with a centromere in the center, while the smaller (p) arms join to form a mini DNA segment with few genes and no centromere which is generally lost by the cell. This effectively changes the chromosome number – a human with a Robertsonian translocation would have $45$‍ chromosomes, with one chromosome containing the information originally carried on the original q arms. Again, the person with the translocation can be phenotypically normal, but complications arise when they pass their genes on to the next generation.

Figure 1. A Robertsonian translocation brings together the long arms of two acrocentric chromosomes.

Down syndrome, also known as trisomy $21$‍, typically happens when a person has $3$‍ copies of chromosome $21$‍ and it leads to mental and physical growth delays. About $4$‍% of cases of Down syndrome actually occur due to a parent with a Robertsonian translocation that involves chromosomes $14$‍ and $21$‍. The karyotype of a parent with a Robertsonian translocation is seen in Figure 2.

Figure 2. Karyotype of a Robertsonian translocation. Attribution: modified from National Human Genome Research Institute, CC-BY-SA 3.0