This article discusses genetic testing; that is, testing that looks at a person’s genetic make-up for a variety of reasons. If you would like to first learn about the basics of cells and DNA, look at our Genetics Information page which contains helpful videos and slide shows. If you already know the basics, you can carry straight on.

Chromosomes, DNA and genes

The total of an individual's genetic information is called their genome. The genome consists of structures called chromosomes that are composed of very long double strands of DNA. Each human cell contains 23 pairs of chromosomes. One-half of each pair is inherited from an individual's mother and the other half of the pair is inherited from an individual's father. Twenty-two of the 23 pairs of chromosomes are called autosomes; the other pair is composed of the X and Y sex chromosomes. The sex chromosomes determine a person’s sex; males have one X and one Y chromosome while females have two X chromosomes.

Chromosomes are located in the part of the cell called the nucleus. The long, double strand of DNA (sometimes called “nuclear DNA”) contained in each chromosome is organised into many subunits of genetic information, with each subunit referred to as a gene. Genes are made up of four different bases (adenine, guanine, thymine and cytosine) which are each linked to a molecule of sugar and a phosphate group, to form a nucleotide. The four nucleotides are abbreviated as A, G, T and C, according to the individual bases. Each DNA strand is made up of a long string of nucleotides joined together in a chain e.g. AATGCCATTGACCC…… The information in the DNA is contained in three letter “words”. For example, if the first A in the sequence is the start of the code, then the first three “words” are AAT, GCC and ATT. It is the difference in the arrangement of these bases on each strand of DNA that leads to the uniqueness of each person’s genetic make-up. The arrangement of the bases in each gene is used to produce RNA which in turn is used to produce a protein. There are approximately 20,000-25,000 genes in a human genome, and expression of these genes leads to the production of a large number of proteins that make up the structure of our bodies and determine how it functions.

There is also a tiny bit of DNA that is not located in a cell’s nucleus but in the mitochondria that are located in the cytoplasm of every cell. Mitochrondria are very important cellular structures involved in the basic functioning of cells, and they contain their own circular piece of DNA. This DNA is called “mitochondrial DNA,” and it in part makes the proteins that are needed by the mitochondria to function properly.

A person’s genotype is their genetic identity, the specific combination of genes that they have in their cells. This does not show in terms of outward appearances. Observable traits or characteristics, such as hair colour or height, are considered a person’s phenotype. Phenotype is coded for by our genes. People’s phenotypes are different because their genotypes are different. Although human genotypes are alike in many ways, small differences make us unique beings in both appearance and genetic make-up. These small genetic differences are called polymorphisms.

Genetic polymorphisms in both nuclear DNA and mitochrondrial DNA help to identify us as individuals. A small number of these differences in our genotype are related to disease or to the inability to metabolise or break down drugs normally. Many polymorphisms are harmless variations that have occurred over time. Genetic variations that may sometimes cause the gene product not to function correctly are called mutations. Mutations in our DNA can occur spontaneously in the individual or be inherited from one or both parents. These genetic variations will be discussed under the specific “Conditions and Diseases” that have a genetic component, such as cystic fibrosis. Sometimes only one nucleotide in a gene is different, and this is referred to as a “single-nucleotide polymorphism". This will be explained in greater detail in the section on clinical genetic testing.

Patterns of inheritance

There are many factors that may obscure or complicate inheritance patterns. These factors in turn affect the way a gene is inherited or expressed.

There are several ways in which an individual’s genetic traits are inherited. These are called “patterns of inheritance” and result in the transmission of a polymorphism or mutation from one generation to the next.

a) Autosomal dominant inheritance
One pattern is referred to as autosomal dominant, in which the transmission of a single altered copy of a gene on one of the autosomal chromosomes is sufficient to cause a certain trait to appear (such as eye colour or a specific disease). The altered gene copy may be inherited from either an individual's mother or father. Individuals with an autosomal dominant trait or disease have a 50-50 chance of passing the altered gene on to their children. Examples of autosomal traits are brown eyes and the ability to roll one’s tongue; examples of autosomal dominant diseases are familial hypercholesterolaemia and Huntington's disease.

b) Autosomal recessive inheritance
A second pattern of inheritance is termed autosomal recessive and requires inheritance of two altered copies of the same gene, one altered copy being inherited from an individual's mother and the second altered copy being inherited from an individual's father, for the trait to appear or the disease to develop. If the individual inherits only one of the altered genes, he or she will not develop the disease but instead will be a carrier, much like his or her parent, and can in turn pass one copy of the altered gene  on to his or her children. An example of an autosomal recessive trait would be blue eyes; examples of autosomal recessive diseases include cystic fibrosis, sickle cell anaemia, and haemochromatosis.

c) Sex-linked chromosome inheritance
There are also patterns of inheritance in which the altered or abnormal  gene resides on either the X or Y sex chromosome, and these are referred to as sex-linked patterns of inheritance. With X-linked recessive diseases, a female carries the abnormal gene on one of her two X chromosomes, but because she possesses one normal copy of the gene, she is not affected. However, since males have only one X chromosome, a single abnormal copy of the recessive gene on his X chromosome (inherited from his mother) is sufficient to cause the disease. Examples include Duchenne’s muscular dystrophy and haemophilia. Rarely, a disease may have an X-linked dominant pattern of inheritance.  Here, a single abnormal gene on the X chromosome can cause the disease to develop in males and females, so that a female is affected and the condition is often lethal in males.

d) Mitochondrial inheritance
It is interesting to note that mitochondrial DNA (or “extra-nuclear DNA”) is inherited only from our mothers. This is referred to as a “maternal mode” of inheritance.

We will also briefly cover genetic testing of microorganisms where this is used in diagnosis of disease. An increasing number of genetic tests are becoming available as a result of recent and rapid advances in biomedical research. It has been said that genetic testing may revolutionise the way many diseases are diagnosed. But genetic testing does not just help a physician diagnose disease. There are a number of different types of genetic testing performed. These include the following:

Identity testing and parentage testing are usually performed in specialist laboratories, not pathology laboratories but will be briefly covered in this article. We will focus on the medical aspects of genetic testing. 

  Last Review Date: September 24, 2016