Chromosomal abnormalities: Translocations in the germline

During meiosis, homologous chromosomes line up and exchange information in the process of crossing over. However, if the chromosomes misalign, the resulting gametes may be unequal in chromosome content and, often, nonviable. Chromosomal rearrangements known as translocations are one major source of misalignment. Translocations can be classified into two main categories: reciprocal and nonreciprocal. Reciprocal translocations involve two chromosomes exchanging genetic information, whereas nonreciprocal translocations, also known as unbalanced translocations, involve the transfer of genetic material from one chromosome to another without a reciprocal exchange. 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 due to inviable gametes.

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 (fusion 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.

Figure 1 Robertsonian translocation bringing together the long arms of chromosomes 14 and 21

For the fusion chromosome, the single remaining functional centromere can come from either of the two original chromosomes involved in the translocation. For example, if chromosomes 14 and 21 are involved in a Robertsonian translocation, the fused chromosome can retain the functional centromere from either chromosome 14 or chromosome 21. The centromere can play a significant role in determining which homologous chromosome it aligns with during cell division (e.g. whether it aligns with chromosome 14 or 21).

The karyotype of a parent with a Robertsonian translocation is seen in Figure 2. Although the fusion chromosome is shown paired with chromosome 14, it could line up with either chromosome 14 or 21 during meiosis, depending on its centrosome and other factors.