Predictive Genetic Testing
Last update: November 2011
Contact: Lisa Tambornino
I. Medical and scientific aspects
The term "genetic testing" and "genetic examination" encompasses various methods that can provide direct insights into the genetic make-up of an organism, also known as its genome (see module Genome). Genetic tests involve the analysis of genes or genetic products. Other methods are available, without DNA analysis, which can be used to obtain information about the genetic constitution of a human being: they include imaging techniques such as X-ray and computer tomography or indeed the mere appearance of a person. Kidneys dotted with numerous cysts, for example, can indicate the presence of a particular hereditary kidney disease.
Genetic tests are examinations conducted for the targeted detection of disease-causing (pathogenic) changes or mutations (see module Mutations) in DNA. In addition to this primary purpose, genetic tests can also be used to establish traits that do not have any disease status. In the broader debate such examinations are frequently referred to as "lifestyle tests"; practical implementations of this potential application have not, however, been observed to date.
Postnatal predictive diagnostics (see module Postnatal predictive genetic testing methods) is used to identify genes or genetic defects (see module Genes and genetic defects) that can lead to disease in later life or dispose a predisposition to such disease. In this context, genetic tests performed in childhood and adulthood (postnatal examinations) should be distinguished from those carried out before birth (prenatal), before implantation (preimplantation diagnostics) or on polocytes (polar body diagnostics); classification is determined by the point in time when such testing is performed.
A genetic test is referred to as predictive if the examination is performed on a person who does not exhibit any symptoms of disease at the time of testing.
Genetic diagnostics used in the context of a tentative clinical diagnosis are thus not included in predictive testing methods. In this instance, a genetic test is performed on an already sick individual in order to confirm or discard a previously presumed diagnosis; thus, for example, a case of unclear childhood myopathy can be diagnosed as spinal muscular atrophy with the aid of molecular genetic testing.
Predictive genetic testing can be used to investigate whether a mutation is present that indicates a predisposition to a disease.
Gene mutations (see module Mutations) are changes in the genetic information on a segment of DNA (see module DNA) that codes for a specific protein (see module Protein). Such a change can occur spontaneously or it may be environmentally induced. Environmentally induced mutations are triggered by environmental factors, such as radioactive or other ultraviolet radiation.
Individuals who test positive, however, need not necessarily become diseased. More than 90% of all mutations have absolutely no effect on the phenotype (see module Genotype / Phenotype) of a living organism they are harmless. These are also described as "neutral mutations" which affect exclusively the genotype (see module Genotype / Phenotype).
Under 10% of all mutations have a more or less strong effect on the phenotype and can lead to diseases. The extent to which a trait is actually expressed in a specific case is referred to as penetrance (see module
Penetrance / Expressivity). The various types of predictive testing techniques are distinguished not by the investigative method used, but rather in terms of their informative power and the quality of the collected data as well as the intended purposes.
Various types of tests are as follows:
- Predictive diagnostics in the strict sense (see module Predictive genetic diagnostics in the narrower sense of the term), on the basis of which the presence of a genetic predisposition can be diagnosed long before onset of a disease.
- Heterozygote tests / screening programmes (see module Heterozygote test / Screening programmes), which investigate whether the status of genetic carrier (heterozygosity) is present, from which autosomal recessive or X-linked recessive (see module Heredities and definition of terms) inheritance of a disease can be inferred.
- Pharmacogenetic tests (see module Pharmacogenetic test), which can provide information about individual tolerance of drugs.
- Susceptibility test (see module Susceptibility test), with the aid of which genetically related intolerances to certain substances can be established.
- Screening programmes (see module Heterozygote test / Screening programmes), which screen larger groups of people (for example specific risk groups) or entire populations rather than individual persons for genetic mutations.
Roughly 3,300 of the now 11,000 investigated genetic diseases can be detected using genetic testing methods. For instance, a big success concerning the recessively inherited Miller Syndrome (see module Diagnosis of the Miller Syndrome) could be recorded recently. Yet onset of the disease can only be reliably predicted in a few cases for example with respect to Huntington's disease (see module Huntington's disease). Further information about clinical symptoms, molecular genetics and scientific publications on the topic of hereditary diseases is available from the Online Mendelian Inheritance in Man website (abbreviated to OMIM (see module OMIM)), an online database of human genes and their known mutations. In principle, any tissue with nucleated cells containing DNA, such as blood, semen, hair, bones or saliva, can be used for testing. Prenatally, nucleated cells can be gained from amniotic fluid; for the purposes of postnatal molecular genetic testing DNA (see module DNA) from white blood cells (leukocytes) of the peripheral blood is normally used. Often, the genetic segment that is to be examined is first amplified using a special method, the polymerase chain reaction (PCR), and then analysed.
In the course of technological developments, new techniques for sequencing could be developed. Knowledge of genetic information can, for instance, be acquired faster, more reliably as well as cheaper by means of the so-called single-molecule sequencing than it is the case with previous methods. DNA-chips further facilitate the simultaneous testing of a large number of different traits.