There is constant progress in the field of genetic testing, which becomes better at detecting the mutations that cause disease. In spite of this, it is not always possible to pinpoint a mutation that is causing a specific condition. This is because a limitation of genetic testing is that it can only detect the known variations (mutations) of a gene, meaning that you have predefined what you are looking for. Analysing the whole genome, on the other hand, not only considers the best known genetic mutations, but the entire genome at the same time, meaning all genes as well as regions outside the genes.
The challenge is then to detect which of a human’s 20 to 25 thousand genes is hiding a variation, which can be causing a genetic condition. The procedure involves narrowing the options down to the most likely genes, which may cause the condition and then examining them more closely. This is done by separating genes using some filters.
It is only necessary to examine the 1 to 2% of the genome that codes proteins, because hereditary conditions in most cases are caused by defects occurring in protein coding regions. This is called exome testing.
The next step can be filtering out so-called polymorphisms, e.g. base substitutions that are common in humans, and are therefore not considered to cause disease. What the test looks for instead is rare or directly ‘private’ mutations, which only occur in one patient and possible their family.
Subsequently a categorisation based on types of mutations that are known to lead to errors in proteins can be carried out. The order of bases in the genes determines how proteins function and mutations therefore have an impact on how they work. We all have numerous mutations in our genes, but most mutations have no significant impact on us.
The next step can be to filter the genes, so that only the genes known to be linked to a certain type of condition are examined.
In addition, it can also be helpful to carry out genome testing of a patient’s relative – both healthy and sick relatives – in order to see which mutations segregates with the condition. By drawing up the patient’s family tree, it is possible to get an overview of how a condition is inherited. In the Faroes we already have a robust register of how Faroese people are related dating all the way back to the 17th century in the Registry of Genealogy.
A lot of work also goes into finding information about the condition, for example in scientific publications.
This diagnostic work is usually a collaborative effort with medical doctors, molecular biologists and bio informatics experts working together. Most genome testing results in one of three different outcomes: In some cases the mutation that is considered to cause the hereditary condition is found. In other cases doctors and other practitioners draw a blank, even though they have searched long and hard. In many cases the process concludes with the detection of a genetic mutation, which is suspected to cause disease, but this cannot be conclusively confirmed, because that variation has never been seen before.
Source: The Danish Council on Ethics