Deletion: Removing information

The majority (65%) of Duchenne patients have a deletion of one or more exons. A normal dystrophin gene contains 79 exons, interrupted by 78 introns (Figure 1). In some Duchenne patients part of the gene is missing (deletion); in the example in Figure 1 exon 48, 49 and 50 are gone. The deletion starts after exon 47, in intron 47 and ends after exon 50 in intron 50. The deletion thus encompasses part of intron 47, exon 48, intron 48, exon 49, intron 49, exon 50 and part of intron 50. However, as only the exons contain the genetic code for protein, usually only the exons that are deleted are mentioned for deletion mutations: in this case this is thus a deletion of exon 48-50

mutatie in de dmd code
Figure 1. Deletion in the dystrophin gene.

Deletions in Duchenne patients disrupt the genetic code of the dystrophin gene. That is because an early stop sign is given to the translation of gene to protein. Thinking back to the comparison that was written in Mutations: a dog has eaten part of the recipe. You have to stop making the recipe because part of the recipe is not readable anymore. This can be seen in Figure 1: exon 47 and exon 51 do not fit. The consequences of this disruption are disastrous.


Figure 2. The consequences of a disruption of the genetic code.

In the top drawing in Figure 2 the original RNA and protein from figure 1 are shown. Below the genetic code is disrupted (in this case by the deletion of two RNA subunits). As each 3 RNA subunits contain the code for one protein subunit, this deletion has huge consequences: instead of the blue-yellow-yellow RNA code, the code is shifted to yellow-blue-yellow, and each subsequent code is also shifted to something else (disruption of genetic code). As a result, aberrant protein subunits are encoded starting at the mutation (green and orange instead of blue and yellow). As the function of a protein is determined by the characteristics of the protein subunits, a protein that contains aberrant subunits is not functional (e.g. it is impossible to build a model car with parts of a model plane).