Our cells are protein making factories. Deoxyribonucleic acid (DNA) is the instruction manual that tells our cells the shape, size, and function of each protein that it makes. Each protein is coded by its own little section of DNA called a gene.

DNA is made up of building blocks called nucleotides. There are 4 different kinds of blocks: Adenine (A), Thymine (T), Guanine (G) & Cytosine (C). The specific order of these nucleotides in a gene forms the instructions, or code, for the cell to follow – like the words of a sentence.

The same way that binary numbers (0 and 1) can encode all our technology, and the 26 letters of the alphabet make up all the words in the English language, the language of our genome, i.e. the complete set of genes in a cell, consists of only 4 characters: A, T, G & C.

Image: “DNA, Chromosomes and Genes” by National Institutes of Health (NIH) is licensed under CC BY-NC 2.0

Some genes remain the same across all humans (and lots of different animal species too!); for example, most of us have two arms, two legs, two eyes, ten fingers & toes, a heart, a liver, etc.

However, there are parts of your genome that are unique to you and your family. These differences are what make you different from everyone else in the world; the shape of your nose, the freckles on your face, your height, hair colour, and much more!

These differences are called mutations, and most of the time they are completely harmless. At some point in the past, nucleotides in the DNA were added, removed, or swapped, thus changing the gene slightly.

If we relate the our genes back to sentences in a book, a mutation is like when there is a misspelling in a word. Sometimes, a change in spelling will not change the meaning of a word:

E.g.: Color –> Colour

In this case, the ‘u’ has been added, but one can still recognise the word as meaning the same thing – in fact, many people use “colour” all the time!

In other cases, a mutation can change the meaning of a gene completely:

E.g. Decrease –> Increase

Here, the “De” has been swapped for “In”, and the meaning of the word has now changed completely. If this mistake was part of an instruction manual, one would be doing the complete opposite of what they should. When these kinds of mistakes or mutations happen in the DNA of a cell, it can have a negative effect on how the cell functions.

Sometimes, when genetic mutations have a negative effect, the resulting protein that your cell makes doesn’t work the way it’s supposed to. This can have drastic downstream effects on the overall function of a cell.

For example, a genetic mutation in a waste-disposing protein might stop it from working properly. In this case, if a cell cannot get rid of its waste, it will eventually die.

When genetic mutations affect the way the cells of the retina work, the cells begin to deteriorate. Over time, this results in a progressive loss of vision. These conditions are called Inherited Retinal Degenerations, or IRDs.

There are many different kinds of IRDs, with hundreds of mutations that can cause them. Knowing your code, or mutation, can help researchers understand exactly what is happening in your cell; which protein is not acting how it should, and if there is a way to slow down, stop, or reverse the process.

If you would like to learn more about IRDs, visit our page here.

Depending on where a mutation is located, and the kind of mutation it is, influences the likelihood of:

1. Inheriting the mutation
2. Being affected by the genetic condition as a result

For this reason, it is very useful for patients to understand the inheritance pattern of their mutation, so as to identify the risk of other family members having inherited the same mutation.

Below are some of the most commonly seen inheritance patterns.

When a mutation in a dominant allele is inherited, the cell will always express the mutated gene, and that individual will show symptoms of that particular genetic condition. We typically refer to this person as an “affected” individual.

So, when gametes are being made, and the chromosome pairs split into separate gametes, 50% of them will have the chromosome with the mutated dominant allele, and 50% will have the other, recessive allele. If an offspring inherits the dominant allele, they will be affected by the genetic condition, and be at risk of passing the mutation on to their own progeny. If they inherit the recessive allele, the individual will be unaffected, and have 0% risk of passing the mutation on.

To learn more about Autosomal Dominant Inheritance, click here to view a video by the Genomics Education Programme (NHS).

When a mutation in a recessive allele is inherited, the cell will not express that mutation in the presence of an unmutated allele, as the unmutated allele will be dominant. As such, protein is made from the DNA of the unmutated allele, and the individual shows no symptoms. This person is however what we refer to as a “carrier” – someone who is not affected by the genetic condition themselves, however can still pass the mutated allele on to offspring. As before, 50% of the individual’s gametes will possess the mutant recessive allele.

If both parents are carriers, and their offspring inherits the mutated recessive allele from both parents, then that offspring’s cells will have no option but to express the recessive allele and as such will be affected. In the case of two carrier parents, there is a 25% probability that their offspring will inherit both recessive alleles be affected by the condition. There is also a 25% probability that the offspring will inherit both dominant alleles, and will not carry the gene. The remaining 50% accounts for offspring that have inherited one dominant and one recessive gene from their parents. These offspring will be carriers, akin to their parents.

If only one parent is a carrier, there is 0% risk of their offspring developing genetic disease, however there is a 25% probability that their offspring will inherit the recessive allele from the carrier parent, and become a carrier themselves.

To learn more about Autosomal Recessive Inheritance, click here to view a video by the Genomics Education Programme (NHS).

Earlier we discussed X & Y sex chromosomes. Here we will explore how inheritance of mutations in these chromosomes differs from the other 22 pairs of chromosomes. When a genetic condition is X-linked recessive, that means that the mutation lies on the X chromosome, and primarily affects XY males, due to them possessing only one X chromosome.

If an XY male inherits a mutated X chromosome from their XX mother, they will develop the condition, because the Y chromosome does not possess an allele for that gene, and cannot prevent the cell from expressing the affected X chromosome. In the case of an XX carrier mother, and an unaffected XY father, offspring have a 50% risk of inheriting the affected chromosome. XY sons that inherit the mutated X chromosome will be affected by the genetic condition, while XX daughters will be unaffected carriers.

For XX females to be affected, both of their X chromosomes must have the mutated gene. One must come from an affected XY father and one from an XX carrier mother. However, due to a phenomenon called non-random X chromosome inactivation, female carriers may display some symptoms of the disease.

A small amount of our genome lies outside of chromosomes, in what we call mitochondrial DNA, Mitochondrial inheritance, also referred to as maternal inheritance applies specifically to genes contained within mitochondrial DNA.

Mitochondria are structures found within cells and responsible for producing energy for the cell. Egg cells and not sperm cells contribute mitochondria to a developing embryo and explains why only XX females can pass mitochondrial mutations to their children. These conditions can affect both males and females and can appear in every generation of a family, but XY fathers cannot pass down these conditions to their children.

The severity of symptoms may vary from one affected individual to another; even within the same family due to a ‘dosage’ effect. This is due to the fact that we have many mitochondria in each cell. In one individual, if only a small proportion of mitochondria in each cell have the mutation, symptoms will be mild. In another individual, if a higher proportion of mitochondria in each cell carry the mutation, symptoms will be more severe.

This short audio-visual by Children’s national Hospital Rare Disease Institute helps to explain the phenomenon of Mitochondrial inheritance: Mitochondrial Inheritance.

Very often, a person diagnosed with an inherited condition has no other family members with the disease. There are several possible reasons for only finding one person affected in the family:

1. The mutation may be a new event in that person,
2. Other family members may have the same mutation, but may have not yet been diagnosed with the condition.
3. Other family members may have a later age of onset, or have milder signs of the disease.

The mutation might also have been in the family for a long time, but by chance, no other family members have been affected. For autosomal recessive disease, carriers may have been present in the mother’s and father’s side of the family for several generations, but a child won’t develop a condition unless both parents are carriers and both pass on a mutation to their child.

Genetic counsellors are health care professionals with specialist expertise in medical genetics and counselling and work as part of a larger health care team. Seeking their support through a genetic testing process can help alleviate concerns and help you adapt to a genetic diagnosis in the most effective way possible.

• Assess the risk of a genetic disorder by researching a family’s history, evaluating medical records, and conducting a physical examination of the patient and other family members when indicated.
• Examine and evaluate the impact of genetic testing from a medical, social and ethical perspective in each case.
• Provide the support and information needed to assist an individual and their family in making a decision about genetic testing.
• Interpret the results of genetic tests and medical data.
• Provide counselling or refer individuals and families to support services.
• Advocate for the patient and their family in the healthcare system.
• Explain the next steps for a patient or their family including possible treatments options.
• Discuss life choices including family planning.
• Advise patients on next steps with regard to disclosing their results to family, employers, and/or insurance companies.