Our genome in a nutshell
Imagine that the human genome was an encyclopaedic collection. It would consist of 23 books, each with two copies, for a total of 46 books. Opening a book would reveal pages with paragraphs – and each paragraph can be further broken down into sentences, words, and individual letters. If this collection of books were our genome, it would consist of approximately 22 000 paragraphs and 6 billion individual letters. Now, imagine that you could shrink all 46 books to fit into a library one-tenth the size of a human hair. Nature has managed this feat – fitting all 46 chromosomes, 22 000 genes, and 6 billion letters of DNA into each one of the trillions of cells that make up our body.
Passing on genetic information
To reproduce, we need to pass on genetic information, which is done via the sperm and egg. Each sperm and egg cell should contain half of the genetic information from each biological parent. When making sperm and eggs, a cell containing 46 chromosomes divides into two daughter cells to produce sperm or eggs. Each pair of chromosomes is divided so that each daughter cell receives one copy of each chromosome. When a sperm cell carrying 23 chromosomes fertilises an egg cell carrying 23 chromosomes, the chromosome pairs unite, and an embryo is created with 46 chromosomes (23 pairs).
Mistakes can happen
Although nature has perfected the packaging of our genetic material into individual cells, errors can occur when making more copies of this information and passing it on, especially when splitting chromosome pairs during the production of sperm and eggs. If the mechanism that separates chromosome pairs during egg production mistakenly places two copies of the same chromosome in one egg, the other egg will not receive a copy of this chromosome. When a sperm cell containing one copy of that chromosome fertilises the egg with two chromosomes, the resulting embryo will have an extra chromosome (three copies instead of two). Conversely, if the egg that is missing that chromosome is fertilised by a sperm cell containing one copy of that chromosome, the resulting embryo will have a missing copy of that chromosome (only one copy). Missing or extra copies of chromosomes can have two outcomes: (1) the abnormal amount of genetic information is not compatible with life, and the embryo (or baby) will fail to develop and result in a miscarriage, or (2) the abnormal amount of genetic information allows for development, but will result in a genetic condition such as Down syndrome.
Time is of the essence
The mechanism that sorts chromosome pairs when making sperm or eggs is prone to increased errors the older one gets – especially in women. The passing on of an extra or missing chromosome comes from the egg 90% of the time. This is why doctors always take the age of the mother into consideration when a woman falls pregnant, as the chances of having a child with a condition like Down syndrome or suffering a miscarriage increase with age.
Why do patients seek fertility treatment?
About one in every six couples of reproductive age will experience fertility issues, with many causes of infertility. One of the reasons why couples struggle to fall pregnant is due to a high incidence of chromosome abnormalities in the embryos they produce.
Couples who suffer from infertility often seek advice from fertility clinics. In the fertility setting, embryos are typically generated outside of the body by obtaining sperm and eggs from the couple. The sperm is used to artificially fertilise the eggs, giving rise to embryos. Once an embryo has developed to a certain stage, it can then be transferred to the patient’s uterus in the hope of resulting in a pregnancy. This process is commonly described as in vitro fertilisation (IVF).
The selection of which embryo to transfer can be tricky. Usually, trained embryologists select embryos based on their appearance. However, not all good-looking embryos are genetically normal, and not all poor-looking embryos are genetically abnormal (and don’t have the potential to give rise to a pregnancy). Therefore, deciding which embryo to transfer based solely on its appearance doesn’t rule out the possibility of transferring an embryo with chromosomal abnormalities.
What can be done to prevent miscarriages and genetic conditions?
Because IVF allows embryos to be generated outside of the body, and each cell of the embryo contains its library of genetic information, it is possible to access and assess the genetic makeup of each embryo. Having the genetic information of each embryo allows for better-informed decisions on which embryo(s) to transfer. A technology called pre-implantation genetic screening (PGS) can determine whether an embryo has inherited extra or missing chromosomes – which would lead to a miscarriage or genetic condition if transferred. Thus, by screening embryos with PGS, the chances of experiencing a miscarriage or having a child with a genetic condition are significantly reduced.