The possibilities to identify the causes of hereditary diseases have increased strongly in the past decade. Although there still are a large number of patients with a genetic disease that can not be diagnosed by genetic tests in the laboratory, more and more genetic diseases can now be identified in our genetic material. The main categories of genetic tests are:

Chromosome analysis
Chromosomes can be made visible under the microscope and studied on blood, skin, amniotic fluid or chorion villi.

Molecular testing
Genes are too small to see under the microscope, but are studied in the laboratory by means of molecular techniques.

Biochemical testing
Biochemical tests can be performed on blood, urine and skin to diagnose inborn errors of metabolism.

Alpha-foetoproteine (AFP) determination
After amniocentesis the level of fetal AFP to determine whether the foetus has a neural tube defect.

Maternale blood screening for Down syndrome
During the pregnancy blood of the mother can be analysed to determine the risk on Down syndrome.

Chromosome analysis
Chromosome analyses are referred to as cytogenetic tests. These can be performed before (prenatal tests) or after (postnatal tests) birth. For postnatal cytogenetic tests usually blood is used, as the white blood cells contain chromosomes.


If blood is not available (eg in case of deceased patients) or one want to sore cells for future use sometimes a skin biopsy is taken; such biopsy is taken to grow skin cells in the laboratory, and isolate chromosomes, proteins, and/or DNA. The cells are lysed in the laboratory so that they release their chromosomes. Then the chromosomes are put on microscopy slides and coloured. Afterwards pictures of the chromosomes are made with a microscope. The chromosomes are then classified according to size and form. Afterwards they are numbered from 1 (largest chromosome) to 22 (smallest chromosome). The 2 sets of 22 autosomes (one of the father, and one of the mother) form 44 autosomes. Additionally we also have 2 sex chromosomes : a man has 1 X  and 1 Y chromosomes and a woman has 2 X chromosomes. A classified chromosome card is called a karyotype. The karyotype of a woman is 46, XX and that of a man 46, XY.



Molecular testing
Genes can be studied with DNA tests. These tests are called molecular tests. It is currently impossible to study all 25.000 genes of a person. Molecular tests will focus at one or a few genes, suspected to carry the mutation(s) causing the genetic disease. Over the last decade the disease gene for many genetic disorders has been identified. Therefore molecular tests to identify mutations responsible for genetic disease can now be performed for a lot of hereditary disorders. Some genetic diseases are caused by a single mutation in a single gene, thereby making detection relatively easy. However, in most genetic diseases many different mutations can be present. In these cases the mutation must be traced for each family separately. This can be time- and labour- consuming and therefore also expensive. The time necessary to complete the test is called turnaround time (TAT); this can vary from one week in urgent and easy cases to 1 year for long genes. Prices of molecular tests are of course also dependent upon the socio-economic status of the country where the lab is located, and may vary in Western countries from 100 to 5000 Euro depending on the size of the gene.


There exist several techniques to identify mutations in DNA. In the picture below DNA fragments (in pink) are separated by gel electrophoresis according to their size. An abnormal pattern might indicate a mutation.


The most important technique to identify mutations is sequence analysis of the gene. This nowadays is performed automatically (see figure below).


Biochemical testing
Some hereditary diseases are caused by a deficiency of a specific protein: these diseases are called metabolic diseases or inborn errors of metabolism. The tests used to diagnose inborn errors of metabolism are called biochemical tests.
One can  exclude inborn errors of metabolism not only by quantification of the specific protein (protein or enzyme studies), but also by quantification of the specific products (metabolites) that are metabolised by the proteins (called metabolite studies). When one suspects an inborn error of metabolism, urine and blood of the patient are collected to perform protein and metabolite studies. Besides blood and urine also a skin biopsy can be used for biochemical testing. Cultured fibroblasts can not only be used to study inborn errors of metabolism, but also for cytogenetic or molecular tests, and this even many years after the biopsy was taken.


Alpha-foetoproteine (AFP) determination
One of the most frequently performed genetic tests is the determination of the level of alpha foeto proteine (AFP) in amniotic fluid. After amniocentesis the level of fetal AFP is always determined. AFP is a fetal protein that circulates in the fetal blood. The AFP level in amniotic fluid is raised when the foetus has a failure of the closure of the abdomen (omphalocoele, gastroschisis) or spine (spina bifida or neural tube defect) because the foetal AFP leaks into the amniotic fluid.


Maternal blood screening for Down syndrome
See Prenatal diagnosis for more info on this subject.