AGP Research: Genetic disorders
1. Basic Genetics
Every cell in our body contains over 6 metres of a molecule known as DeoxyriboNucleic Acid (DNA).
DNA is packaged into small structures known as chromosomes. Our chromosomes are arranged within the cell as 22 pairs (called autosomes) and two sex chromosomes (X and Y). Males have one X and one Y sex chromosome, whereas females have two X chromosomes.
Together these 46 chromosomes carry all of the information necessary for you to live, grow and function. They are often referred to as the genetic blueprint. (See also: Figure 1 Word document).
In total our chromosomes contain approximately 30,000 genes pasted together end to end. A gene is defined as a small length of a chromosome which contains all the instructions needed to make a single protein.
Everybody’s genes are slightly different and it is this genetic variation that makes you the way you are. For example, some people have genes for brown eyes, some for blue eyes; some people have genes which make them tall, some people have genes which make them short.
Your individual combination of genes determines what you will look like and, to a certain extent, your chances of developing common illnesses, such as heart disease.
The DNA in our cells is a double-stranded molecule arranged in the well-known "double helix" structure. Each of the two DNA strands is made up of four chemical bases (or nucleotides): adenine (A) and guanine (G), cytosine (C) and thymine (T).
The two DNA strands are connected to each other by chemical pairing of each base on one strand, to a specific partner on the other strand: adenine (A) pairs with thymine (T), and guanine (G) pairs with cytosine (C). These A-T and G-C pairings are referred to as base pairs. The DNA in each our cells is made up of an estimated 3.2 billion base pairs.
2. Inheritance
Of our 46 chromosomes, we inherit 23 from our mother and 23 from our father. The chromosome which is passed on from each parent is randomly chosen and this is what generates differences in our children.
With 23 pairs of chromosomes, the number of possible combinations of chromosomes which can be passed onto our children is 223 –which is 8,388,608. So the chances of our children being genetically identical would therefore be 1 in 8,388,608.
But the variation does not stop there. During the production of eggs and sperm, our chromosomes become entangled with each other and can cross over, swapping parts of genetic material between chromosome pairs. This means that even cells with the same array of chromosomes will vary slightly, and that children actually inherit a mixture of both of your chromosomes from each pair.
Because this crossing over of chromosomes occurs in a random manner the number of combinations of chromosomes in sperms and eggs is infinite and the chances of any child inheriting exactly the same chromosomes is therefore billions to one.
The one exception to this is identical twins. These arise from the division of a fertilised egg early during pregnancy to form two genetically identical babies.
- See also Figure 2 (Word document)
3. Single gene (Mendelian) disorders
Some diseases are caused by mutations in a single gene. For these disorders the pattern of genetic inheritance is clear and we are able to predict the chances of having another child with the same disorder.
If you inherit one or two copies of the mutated gene then you develop the disorder. If you inherit two good copies of a gene you do not develop the disorder.
There are different patterns of inheritance depending on whether the gene with the mutations lies on an autosome (one of the 22 pairs of chromosomes) or one of the sex chromosomes (X and Y).
For genes found on an autosome:
If only one copy of the mutated gene is required for an individual to be affected, inheritance is termed autosomal dominant.
If both copies of the mutated gene are required, then inheritance is termed autosomal recessive. Huntington's disease is an example of an autosomal dominant disorder. (See Figure 3 , Word document)
For genes found on a sex chromosome:
If only one copy of the mutated gene is required for an individual to be affected, inheritance is termed X-linked dominant (if on the X chromosome) or Y-linked recessive (if on the Y chromosome).
If both copies of the mutated gene are required for an individual to be affected, inheritance is termed X-linked recessive or Y-linked recessive.
4. Complex genetic disorders
Other disorders do not appear to be inherited as a single gene disorder. Instead they may be caused by a number of different genes which combine and interact with environmental factors to produce an overall risk factor for developing the disorder. This is known as a complex disorder.
Autism is one example of a complex disorder.
- See Figure 4 (Word document)
A trait is complex at the genetic level if it does not display a classical Mendelian inheritance pattern that can be attributed to a single locus.
Unlike single-gene disorders, complex diseases are often not caused by mutations that disrupt genes, but rather by normal variations within genes.
Everybody’s genes are slightly different and it is this variation which determines what you will look like and to a certain extent, your chances of developing heart disease or other common illnesses.
