Genetics – EDI Network

DNA (Deoxyribose Nucleic Acid) is our genetic information and contains all the instructions to make a human and for our bodies to function correctly.

Your DNA is like your thumbprint. It is yours and yours alone. Unless you have an identical twin, no one else on the planet has exactly the same DNA as you.

So, what is DNA?

Very simply, DNA is the substance which carries the code or language of the body’s instruction manual. Our bodies are made up of millions of cells, but we all began as a single cell.

In the ovaries of the female reproductive system are the egg cells. If a sperm is successful in fertilizing the egg a series of cell divisions take place, it first divides into two cells which in turn divide to give four cells and so on. The fertilized egg now becomes an embryo and moves down the fallopian tube towards the womb where it will grow and develop.

Through this amazing process supported by the nurturing environment of our mother’s womb, most of us end up the right shape with all our organs in place and functioning as they should.

Our DNA is found in the centre (nucleus) of each cell in our body. It is packaged into chromosomes just as a large book comes in volumes. There are 23 pairs of chromosomes, 46 in total, in each chromosome the DNA is organised into genes. Your chromosomes contain about 20,000 genes. Each gene contains the information needed for a cell to perform a particular task,

How does something so small contain all the instructions to make your whole body and keep it working? That is answered in the chemical makeup of DNA. If you think of your genome (all your chromosomes) as the book that makes you, then the genes are the words that make up the story. The cells use the information in the genetic instruction to make proteins, which do most of the real work in the body. The DNA in your genes tells the cell what amino acids (the building blocks of protein) to put together to make the particular protein coded for by each gene. There are only 4 different letters that make up the genetic instructions; these “letters” are called DNA bases: adenine (A), guanine (G), cytosine (C), and thymine (T). It’s hard to believe that an alphabet with only four letters can make something as wonderful and complex as a person!

Each code of 3 letters tells the body which amino acid is needed next in the protein. There are 20 amino acids in total, which seems hardly enough to produce the huge variety of proteins you need to build an organism. But because the amino acids can be arranged in any order or length, there’s a staggering number of different possible combinations – too many to even imagine!

So, what can go wrong?

Genes are the material “stuff” in which the genetic instructions are written (the paper and ink). If there is a change or spelling mistake in the writing of the instruction manual, then the body is unable to function correctly because it has not received the correct instructions. The functioning of our bodies requires that many thousands of genes work together. Changes or spelling mistakes in different genes have resulted in many different genetic conditions, some of which cause the features of Ectodermal Dysplasia. The effect of a change in our genetic code will depend on what the change is and which gene the change is in.

It is very important to remember that a person cannot choose or modify the genes that he or she has, and that the events of pregnancy do not change the genes. Thus, parents who have a child with ED should not think that they did anything to cause the change in the gene and should not blame themselves in any way for having a child with a genetic disorder.

Looking Ahead

Advances in human genetics are expected to benefit us in many ways. Improved understanding of the genetic basis of genetic conditions will, in the long term, lead to better treatments. Many families find it helpful just to understand what has occurred and why.

We cannot answer all the questions you might have, but to understand more about genetics see inheritance patterns below.

Ectodermal Dysplasia Inheritance Patterns

Ectodermal dysplasias can be inherited in different patterns. To understand these patterns, it is important to understand a little about how our DNA is packaged into chromosomes which are like volumes of DNA. They come in pairs, with one of each pair coming from each parent in the egg or the sperm. There are 23 pairs in all: the sex chromosomes and the autosomes. Sex chromosomes, the X and the Y chromosomes, are involved in determining the sex of an individual (i.e. male or female) but also have many other functions. A female has two X chromosomes; a male has one X and one Y chromosome. Autosomes are all the rest of the chromosomes and are the same in males and females. The autosomes are numbered according to size. Chromosome number 1 is the longest and chromosomes numbers 21 and 22 are the shortest.

An autosomal gene is a gene located on a numbered chromosome and usually affects males and females in the same way. If a DNA change occurs in only one of the pair of genes and this causes a health condition, it is called an autosomal dominant condition. If a health condition only occurs when both copies of the gene are changed, this is called an autosomal recessive condition.

An X-linked gene is located on the X chromosome and changes in it will often affect males and females differently. A change in a gene on the X chromosome will often affect a male to a greater extent than it does a female. The Y chromosome has few genes apart from those involved in making an embryo male and promoting male fertility.

Autosomal Dominant Inheritance

Some cases of Ectodermal Dysplasia occur when a single altered copy of the gene is present, as this is sufficient to cause Ectodermal Dysplasia in the person who carries it despite that person having another, intact copy of the same gene. When we have children, we pass on half our genetic information. Therefore, a person affected with an autosomal dominant Ectodermal Dysplasia will have a 50% (1 in 2) chance of passing the disorder on to each of their children regardless of the gender of the parent or the child. This is shown in the diagram below:

Autosomal Recessive Inheritance

In some types of Ectodermal Dysplasia both copies of the relevant gene must be altered before an individual has Ectodermal Dysplasia. We all have some changes in our genes and when an individual by chance has a change in a single copy of such a gene they are known as a carrier and are usually unaffected. If by chance two individuals who carry a change in the same gene have children together, there is a 1 in 4 chance of a child inheriting both altered copies of the gene from both parents. In this case we would expect that child to have Ectodermal Dysplasia. This is shown in the diagram below:

X-Linked Recessive Inheritance

Men and women have different sex chromosomes. Men have an X and a Y chromosome and women have 2 X chromosomes. The Y chromosome is rather small; it makes the child male but has far fewer genes than the X chromosome. Therefore, women have 2 copies of the genes on the X chromosomes whereas men have only a single copy. If there is an alteration in a gene on the X chromosome that has caused Ectodermal Dysplasia, it will usually cause more symptoms in a male than a female. A girl has a second X chromosome which carries a working copy of the gene; this may compensate for the malfunction of the changed gene and dilute some of the symptoms.

Despite this, however, an alteration in a gene on the X chromosome can often show in a female because only one of the two genes will be active in any one cell in the body. In fact, a female has patches where she uses the genes on one X chromosome and other patches where she uses the genes on the other X chromosome. Just which X chromosome is active in any one area on the body is random – it is down to chance.

A Mother affected in this way will have a 50% (1 in 2) chance of passing the disorder to each of her children regardless of the gender of the child, although a girl would be less likely to show signs of the condition.

A Father affected in this way will definitely (with a probability of 100%) pass the disorder to all his daughters and to none of his sons. This is because, if he passes on his X chromosome (with the genetic change) to the baby, the baby will be a girl (and affected). In contrast, if he passes on his Y chromosome, the baby will be a boy (and unaffected).

This X-linked (or sex-linked) pattern of inheritance is shown in the diagrams below:

X Linked Dominant

The X-Linked Dominant inheritance occurs when a single altered copy of the gene is enough to cause a disorder in the person who carries it, whether or not there is another, intact copy of the same gene.

A Mother affected in this way will have a 50% (1 in 2) chance of passing the disorder on to each of her children regardless of the gender of the parent or the child.

It is important to remember that not all individuals will have inherited a changed Ectodermal Dysplasia gene from one or both of their parents. In this case the disorder is classed as a “de novo” (new) genetic alteration. When a child has an Ectodermal Dysplasia syndrome and the parents are shown by molecular diagnosis (through blood samples) not to be carriers of the syndrome, there is only a very small chance that the genetic alteration will be present in another child of the same parents. The affected child however, will have a chance of passing the disorder to their children.

Statistical probabilities are all very well when being reassured by comfortingly low odds (often the case after genetic counselling), but it is not much help to those facing a high chance of an affected child. People often want to know whether they are a carrier or not; whether the developing baby is affected or not. All else is just agonising uncertainty. Only recently, through the advances of molecular genetics, has genetic testing been able to determine the precise genetic alteration in an individual affected by Ectodermal Dysplasia. Finding the precise genetic alteration not only confirms the precise type of Ectodermal Dysplasia in an individual, but also means that a family member can be given more accurate information about the chance of a baby being affected. They may also be offered early prenatal diagnosis if there is a significant chance of having an affected baby and they wish to know.

Consanguineous Marriage

‘Consanguineous’ means ‘being of the same blood’ and consanguineous marriage is marriage between blood relatives, usually defined as marriage between people who are second cousins or closer, often referred to as cousin marriages.

Being married to a cousin is not the reason that a child is born with a disability. Most babies born to cousin couples are healthy. However, cousin marriage increases the risk of birth defect and those genetic diseases inherited in the autosomal recessive pattern. The fact that parents are related to each other makes it more likely that they will pass the same altered gene to a child, who will be affected because they have this in a double dose. Marriage between first cousins increases the risk of this happening from the 2-3% that everyone faces to 5-6%. This risk is somewhat higher than for other people but in absolute terms is still small.

When a cousin couple have a healthy child, as happens most of the time, this may be because they do not have the unusual gene, or because that child did not inherit the unusual gene from both parents.

Check with you own countries health service to see if Prenatal testing, Chorionic Villus Sampling, Amniocentesis and Non-Invasive Prenatal Diagnosis are available.