Our bodies are made up of thousands of cells. Almost all cells in the body contain a complete set of genes (known as the genome) which can be thought of as a set of instructions or recipes for building and maintaining our bodies.
There are around 30,000 different genes altogether and we have two copies of each one. They are made of a chemical called DNA and contained inside larger structures called chromosomes. Most people have 23 pairs of chromosomes (46 in total). One of each pair comes from the mother and the other from the father. When each of us has a child, we pass on one of each pair of genes and chromosomes to the child. 22 pairs of the chromosomes are the same in men and women and are numbered from 1 (the largest pair) to 22 (the smallest pair). These 22 pairs are known as the autosomes. The 23rd pair are called sex chromosomes because they determine whether a person is male or female: women have two X chromosomes and men have one X chromosome and a smaller Y chromosome.
One way to explain the relationship between cells, chromosomes, genes and DNA is to imagine each cell as having a library of information at the centre of it. The chromosomes are like long shelves, each containing thousands of books. Each gene is like a separate recipe book, giving information on how to make one particular protein or substance needed by the cell. The DNA is like the separate letters and words within the books.
If a gene is altered, it can cause a genetic condition or disease. This gene alteration is sometimes known as a mutation. We all carry several altered genes – probably about 3 or 4 on average. You can think of these alterations as being like a word spelt differently somewhere in the book or perhaps a whole page missing or duplicated: any change that means that the instruction book cannot be followed as usual.
Imagine making a sponge cake where the cocoa is missing from the ingredients: you would still have a cake, but it would no longer be chocolate flavour. This gives a visual picture of how a gene alteration might affect what the gene is coding for.
Some genes are inherited in different ways between men and women. Also, different genes make proteins that work in different ways within the cell so an alteration in a gene will not always show the same sort of effect. Both these facts mean that altered genes show different patterns of inheritance. The different patterns of inheritance are explained in the next section.
There are four main ways in which genes can be inherited:
For many genes, probably the majority, having a second working copy of the gene is enough to make up for an altered copy so that person may never know that they carry it. In this case, this is known as recessive inheritance: the altered gene is recessive to the working gene.
With recessive genes, it is only if someone inherits two altered copies of the same gene, one from each parent, that the effect of the altered copies would be seen. Some relatively common genetic conditions that are inherited in this way include cystic fibrosis and thalassaemia. Deafness can also be inherited in this way. There are also other inherited characteristics that are inherited in this way such as blue eyes or red hair.
If someone has a recessive condition then both of their parents must carry one altered copy of the gene (unless one parent carries one altered copy and the other carries two altered copies i.e. also has the condition, but this would be much less likely). Someone who has one altered copy is said to be a carrier for that particular altered gene.
If two parents are both carriers then, as explained above, it is possible that they could both pass on their altered copy of the gene to a child. However, there are other possibilities: as you can see from the diagram, they could also both pass on their working copy of the gene or one could pass on their altered copy and the other pass on their working copy or the other way round. There is a 1 in 4 chance of each of these gene combinations each time that the couple have a child. This means that there is a 1 in 4 chance that this child would have the condition, a 2 in 4 chance that the child will be a carrier like their parents and a 1 in 4 chance that the child will not inherit any altered copies of the gene.
Autosomal recessive inheritance
A person has to inherit an alteration in both copies of a recessive gene in order to have the condition.
A person who has one altered copy and one working copy of the gene is known as a carrier for that particular altered gene.
If two people who are both carriers for the same altered gene have children together, they have a 1 in 4 chance in each pregnancy of their child inheriting two copies of the altered gene and having the condition.
Picturing how a recessive gene works
Some altered genes are dominant. In other words, if someone has one altered copy of a gene then it can cause an effect or an illness even though they also carry a working copy of the gene: the altered copy is dominant over the working copy and this is known as dominant inheritance.
In some dominant conditions, it is possible to inherit an altered gene without showing any signs of the condition: in other words, the gene is not fully penetrant. Conditions caused by dominant genes also tend to be more variable than recessive conditions so even within a family, some individuals may show different signs of the same dominant condition. Some dominant conditions are known as ‘late onset’. In other words, they only affect individuals in adulthood. Someone who carries a gene for a dominant condition, but has not developed any signs or symptoms of the condition can also be known as a carrier. However, unlike carriers of a recessive condition, with some dominant conditions there may be a chance that they will still develop signs themselves in later life. In some families, only one person has the dominant condition. This may be because a new mutation (a change which arises for the first time) has occurred in either the egg or sperm that went to make that child.
Examples of genetic conditions that are inherited in a dominant way are Huntington’s disease and Neurofibromatosis type 1 (NF1). Deafness can also be inherited in this way and we will return to this later. Again, there are also other characteristics that can be inherited in this way, such as the ability to roll your tongue.
If a parent carries an altered gene for a dominant condition, each of their children has a 50% or 1 in 2 chance of inheriting the altered gene. This chance is the same for each child, regardless of their sex. The diagram makes this clearer.
Autosomal dominant inheritance
A person only has to inherit one copy of a dominant altered gene to have the condition.
Dominant conditions tend to be more variable in their penetrance (how often a carrier shows signs of the condition) and their effect (different people, even within one family, may have different features of the condition).
If a person who is a carrier for a dominant altered gene has children, there is a 1 in 2 chance of their child inheriting the altered copy of the gene.
Picturing how a dominant gene works
Imagine that a different recipe describes how to make potato soup. One word is altered in one of the two copies of the recipe so it says tomato instead of potato. Although there is another unaltered copy of the recipe, the tomato in the first copy is enough to give a tomato flavour to the soup.
X-linked conditions occur when an altered gene is located on the X chromosome rather than on one of the autosomes (the chromosomes carried by both men and women). At the beginning, it was explained that the usual pattern of chromosomes is that women have two X chromosomes and men have one X chromosome and a short Y chromosome with very few genes.
If the gene is a recessive gene, then a woman who carries an altered copy will either have no signs of the condition caused by that gene or will have minor signs of the condition. This is because she has a second working copy on her other X chromosome which can compensate completely or to some extent. She is said to be a carrier of that X-linked condition.
If a man has an altered gene on his X chromosome, then he will have the condition as he has only one X chromosome and therefore only one copy of that gene.
If a woman carrier has a boy, there is a 50% (1 in 2) chance that the boy will inherit her faulty copy of the gene and have the condition. If she has a girl, there is a 50% (1 in 2) chance that her daughter will inherit the faulty copy and be a carrier like her mother.
X-linked recessive conditions affect men more often and more severely than women because men only have one X chromosome and women have two X chromosomes so usually have a second working copy of the gene.
X-linked dominant conditions can affect both men and women, but can still be less severe for women.
A woman who is a carrier for an X-linked condition has a 1 in 2 chance in each pregnancy of a son having the condition and a 1 in 2 chance of a daughter being a carrier for the condition.
Men who have an X-linked condition will pass on the altered gene to all their daughters, but none of their sons.
A father determines the sex of his child because he either passes on an X chromosome (and has a daughter) or a Y chromosome (and has a son) whereas all children inherit an X chromosome from their mother. This means that, if a man has an X-linked condition, then all his daughters will inherit the altered gene copy from him and be carriers themselves. Because men do not pass on their X chromosome to their sons, none of their sons will have the same X-linked condition as their father.
Haemophilia and Duchenne muscular dystrophy (a severe type of muscular dystrophy) are examples of genetic conditions that are inherited in an X-linked recessive way. Red-green colour blindness is also inherited in this way.
A few conditions are caused by a dominant altered gene on the X chromosome. In this case, both men and women can show signs of the condition if they inherit a faulty copy of the gene. For many of these conditions, males are still affected much more than females. Fragile X syndrome, which causes learning difficulties, is sometimes described as a dominant X-linked condition because both men and women can have learning difficulties. However, many women do not have learning difficulties and for those that do, they are usually mild whereas men with Fragile X usually have moderate learning difficulties.
There are both X-linked recessive and dominant genes that can cause deafness and we will return to this later.
Sometimes boys are born with X-linked recessive conditions even though their mothers are not carriers. When this happens, it is particularly important to get specialist advice about the family’s individual situation. One possible reason for this is that the mutation or gene change occurred for the first time in the egg or sperm that went to make up that child.
As explained above, most of our genetic material is stored on our chromosomes. The exception is a few genes which are carried on a separate little stretch of DNA within the mitochondria. This stretch of DNA is known as the mitochondrial genome. Mitochondria are the powerhouses of the cell: little bodies within the cell that generate the energy that the cells need to function. There are many mitochondria in each cell, each with one copy of their genome. Mitochondria are only passed on by the mother because the egg is very big compared to the sperm. This means that, if a woman carries an altered gene in all or some of her mitochondria, she will pass on the altered copy to all her children in some or all of the mitochondria that they inherit. Because the number of mitochondria that inherit the altered gene copy is variable, the effect of the altered gene will also be variable. If a man has a mitochondrial condition, he cannot pass it onto his children. Because there are not many genes on the mitochondrial genome, these conditions are rare, but important for genetic specialists to be aware of. Deafness can occasionally be inherited in this way.
08-Dec-2015 5:39 AM (AEST)