During fertilisation the egg cell merges with the sperm cell and a single cell results with - if all goes well - 46 chromosomes: 23 from the mother and 23 from the father. In the egg cell the 23rd chromosome is by definition an X; a sperm cell, however, has either an X or a Y. It is therefore the sperm cell that determines the gender of the embryo: if it adds an X, the embryo will be XX (a girl), and otherwise it will be XY (a boy).
We inherit our genes through the chromosomes, so logically we also have two copies of these. We refer to the two variants of the same gene as alleles.
If a particular characteristic or disorder is linked to a single gene, it is referred to as monogenic. If multiple genes are responsible we call it multigenic and if environmental factors also have an impact it is called multifactorial.
Degrees of severity in conditions
Not every genetic condition is expressed to the same extent or at the same time in every affected individual. We can identify three factors that influence the severity of the condition.
Mosaicism: defect is not present in all cells, always expressed in cells with a defect, so there are gradations from mild to severe
Penetrance: defect is present in all cells but not always expressed, depends on the individual but difficult or impossible to predict who will be affected, so it is more of a lottery.
Expression: defect present in all cells, always expressed but in a variable way, e.g. Marfan syndrome is a connective tissue disorder: connective tissue is found in virtually all organs and parts of the body, which explains the major differences in expression.
A person with a genetic disorder may have both normal and abnormal cells. We call this phenomenon mosaicism and it is the result of an error in cell division affecting a number of cells during early development of an embryo or fetus.
Mosaicism is seen mainly at the chromosomal level, particularly in numerical disorders such as Down's, Klinefelter's or Turner's syndrome.
Mosaicism also occurs at the DNA level, e.g. in Fragile X syndrome, due to the (variable in the case of mosaicism) expansion of a trinucleotide repeat.
Depending on the percentage of cells affected, the genetic disorder will be expressed more or less severely. In people with one of these symptoms we may also be able to see this visually and medically (more or fewer external characteristics and symptoms).
In some cases a single gene defect may result in different clinical pictures in different individuals, even within the same family. We call these disorders with variable expression. Patients always have symptoms, although these vary from mild to severe.
Examples include Marfan syndrome and neurofibromatosis.
Where penetrance is incomplete, the disorder may or may not be expressed. The frequency with which the gene defect occurs in individuals is usually expressed as a percentage. Hereditary haemochromatosis (=a disease in which iron accumulates) is one example of a disorder with variable penetrance.
Some genetic disorders are only expressed later in life, often after the reproductive years. This means that a person who may develop the disease has still been able to pass on the disorder to his descendants before he or she developed the symptoms.
This is the case, for example, in Huntington's disease and in cerebellar ataxia (a movement disorder caused by an abnormality in the brain).