Genetic Counselling

Image: DNA (Fire Joust)

What runs in your family?

Spark up a conversation about inheritance and you may just find yourself in a debate about the recent budget changes, which will have more than a few people grumbling. Of course if you were to be passing on your estate after 2020, I’m sure your relatives would be thanking Mr. Osborne for a lovely tax-free £1 million estate in their name. Thankfully for those who need a break from politics, that’s not the topic here.

You inherit much, much more than mere assets of monetary value (or not so mere, depending on your family name of course). The inheritance in this case is the kind from which of all of your attributes, good or not so good as the case may be as you will see, are sourced. A number of your characteristics form discrete variables – either present or not – for instance eye colour or gender. Other characteristics, such as intelligence and athleticism, are not clear-cut and so follow the age-old argument of nature vs. nurture (more specifically the rubber band hypothesis). Metaphorically speaking, the length of the rubber band is determined by your genetics, but how far it is stretched is down to your upbringing. Let’s put it this way; picture yourself an aspirational marathon runner. The more you train, the fitter you become and therefore (hopefully) the faster you are. But alas, you may be at the peak of your physical fitness (in which the band is fully stretched), but a runner who has a long line of world champion marathon runners snaking up their family tree will have drastically better odds at beating you. Their metaphorical genetic rubber band was longer than yours.


A genetic-what now?

Following this logic, some of us may be lucky enough to naturally have the build of the perfect marathon runner. There are those of us that are naturally predisposed to develop a disease over the course of our lifetime. The lesser known yet fast growing profession of genetic counselling tasks itself with consulting these individuals at heightened risk of genetically linked disease. As the name suggests, genetic counsellors are medical professionals who have been trained specifically to discuss the risks and factors involved in the development of genetically linked diseases.

The role of a genetic counsellor is defined by the American Society of Human Genetics as “a communication process that deals with the human problems associated with the occurrence, or the risk of occurrence, of a genetic disorder in a family”. It is the job of a genetic counsellor to act as the middleman between the laboratory and an individual or family, translating the jargon thrown up by genetic testing into straightforward, amenable information. Such consultations inform patients about risks of adult-onset disorders such as Huntington’s disease, the risk of conceiving a child that will suffer from or develop a particular disease, or the risk of developing a cancer of some kind. More to the point, a genetic counsellor is there to allow clients to make informed decisions through the practice of non-selective counselling. For instance, a family at high risk of conceiving a child who will suffer from a debilitating disease will be able reassess their options, or put in place measures that will give the child the best quality of life.


The genetics behind the risks

Now for the science. How do a seemingly healthy couple have a high risk of conceiving a child with a genetic disorder? Even more interestingly, how are the risks of developing a genetic disorder calculated in the first place? Let’s go back to the beginning, even before birth, to the fusion of the egg and sperm that made you. Your genome contains two sets of complete genetic information; one from your father’s side and one from your mother’s side, each set possessing all of the information required to make you ‘you’. Strictly speaking, this information is contained within regions of DNA called genes with each gene acting as a code for a biomolecule called a protein. These proteins more or less produce all of your individual characteristics. The human genome consists of 20,000 (or so) of these genes, neatly packaged into 23 discrete units of inheritance called chromosomes.

In a normal body cell your two sets of the genome make up 23 pairs of chromosomes (46 in total). When a cell such as a sperm or egg (known as a gamete) is formed however, the amount of genetic information present within it is only half of that. Your parents are not genetically identical (one would assume) and so these two sets of chromosomes in one of your body cells, which both contain the same genes (note they are the same and not identical), must vary in some way, producing the natural variation that makes everyone on the planet a unique genetic individual. As previously alluded to, there must be variation within the genes themselves. Genes are sections of DNA that code for a specific characteristic, an albeit over-simplified example would be eye colour. The OCA2 gene, found on chromosome 15, is the main determinant for the colour of the iris. All humans on the planet possess this gene. However, not all humans have the same eye colour. How is this possible? Genes themselves are made up of DNA, which in itself is a very long sequence of four chemical bases (adenine, guanine, cytosine and thymine). This sequence acts like a recipe, encoding a protein that gives rise to a specific variant of a characteristic. These sequences can vary slightly from each other, which leads to variation we see in eye colour. These variants of genes are known as alleles.

This is where things get interesting. Have you ever wondered how certain traits can seemingly skip generations? If a body cell has two sets of a complete genome, and a gamete has one complete set, then it follows that to produce a sperm or an egg, the chromosomes that make up that complete genome, which you yourself inherited from both of your parents, must be halved. In fact, they are not just split into their respective maternal and paternal counterparts; they are randomly mixed, shuffled and then distributed evenly, but remaining always on the correct chromosome. What are produced are gametes that contain the full collection of 23 chromosomes, possessing slight variations of each gene depending on which parental side they originated (i.e. the generation above you). This random reshuffling of genetic material is why all siblings, except identical twins, vary genetically. If you were then to conceive a child, the DNA you donate would be a mix match of the DNA passed onto you from either of your parents. This, ladies and gentlemen, is the scientific origin of the phrase “skipped a generation”.



Pedigree diagram showing the inheritance of cystic fibrosis: Pedigree diagrams are used by genetic counsellors to determine the occurrence of genetic disease in a family. Just like in a family tree, each shape represents an individual, (squares for male and circles for females) with each branch showing the migration between generations. Unlike this diagram however, pedigree diagrams available to genetic counsellors do not possess gene carrier information and so this must be determined from the incidence of sufferers as only these cases are explicit. As you can see, in the first generation there is one CF sufferer. The disease can then be seen to skip the 2nd generation, before arising again in the 3rd generation.


Here endeth the crash course in genetic inheritance- for the most part. When you understand how genescan vary and how they can be are inherited, you can build into the idea that different people can have increased risk of passing on faulty genes to their children. If one of your parents passed on a faulty version of a gene, complications will only normally arise if you inherited a faulty version of the same gene from your other parent as well. An individual with at least one healthy copy of the gene will appear healthy, as the healthy gene masks the inactivity of the faulty one (in the case of recessive alleles as apposed to dominant alleles, such as in Huntington’s disease which require only one faulty gene to produce the disease). The presence of a faulty version of that gene will however make them a carrier for that genetic disorder.

An eloquent example of the effect of gene carriers is cystic fibrosis. CF is a disease in which the mucus lining the various tracts within the body, notably the airways, is thick and difficult to expel. The cause is a faulty gene located on chromosome 7, coding for a protein which allows water to move from body tissues into the mucus and dilute it, making the mucus easier to move. Possessing one faulty copy of the gene does not make you a sufferer, due to the presence of a functioning copy on the adjacent chromosome 7 inherited from your other parent. However, due to the random nature of inheritance, there is a 50% chance that you will pass on this faulty gene to your offspring. If you were to conceive a child with another carrier of the faulty gene, whose chances of passing on the faulty gene are also 50%, there is a 25% chance that your child would possess two copies of the faulty gene and would therefore suffer from cystic fibrosis. A scary thought, as there would be no way of knowing that either of you had the faulty gene until it is too late. This is one aspect of a genetic counsellor’s role – to translate the statistical risks attained from genetic tests and pedigree diagrams into clear cut information; an informative set of tools that allow the family to make their own choice based on their own ethical, moral and religious beliefs.


My counsellor and me

A visit to a genetic counsellor can go one of many ways, depending on the case. The outcome may be treatment; therapeutic, curative, preventative or in some cases, an opportunity for those concerned to grieve and seek counselling. This is always at the discretion of the individual or family, owing to the idea of non-directive counselling. Genetic counsellors take up a pastoral role within the harshly factual world of genetics. The premise of counselling is to allow the patient to come to terms with the facts and put in place a course of action that not only concerns their physical health, but also maintains their psychological and social wellbeing.

How do genetic counselors convey such information? It cannot be denied that genetic counselling is a numbers game; being in the business of genetics you cannot get away from the comparison of an individual’s risk to the risk of John or Jane Doe. Within the profession, however, the effectiveness of quoting statistics is heavily debated. The answers to some questions are only ever ‘yes’ or ‘no’, like in the case of adult-onset Huntington’s disease. However, for issues like cancer or passing on a faulty gene, the genetic dice make it difficult to move away from the numbers.


If the average chance of someone developing lung cancer at the age of 50 is 2%, but you are informed that yours is 25%, it is obvious that there is something in your genes making you predisposed to develop lung cancer. But this doesn’t actually mean you are definitely going to develop lung cancer; more that by living an average lifestyle you are 12.5 times more likely to. This is the problem quoting statistics. Numerous studies into the ‘objective risk’ and risk perceived by patients point to the fact that many are unable to retain statistical information or to actually understand what the numbers mean for them. It is therefore pleasing that many genetic counsellors tailor their consultations to the preferences of the patient. A statistician may very well be right at home having numbers quoted to them. But for those who are not so keen on them, using numbers less explicitly and more implicitly as a means of conveying the best course of action is seen to be much more effective, and is being used more and more as the profession moves forward.


What does the future hold?

As the bank of genetic links to disease expands, so too does the scope for counselling. Perhaps more exciting, yet slightly intimidating at the same time, is the promise of storing genetic profiles on record to be accessed by both clinicians and counsellors. With this and other growing fields such as pharmacogenomics tailoring treatment to individual people, it is inevitable that questions of ethics and patient privacy will become increasingly more prominent. What can be said for now is that genetic counselling helps thousands of people worldwide learn about and take early action against genetically linked diseases, and could very well become the forefront of clinical counselling in years to come.