Types of Genetic Testing
Genetic tests look for changes in a person's genes or changes in the amount, function, or
structure of key proteins coded for by specific genes. Genetic tests can look at the
DNA or RNA that play a role in certain conditions. Abnormal generic test results could
mean that someone has a genetic disorder or tendency to have a disease.
The following information describes the three main types of genetic testing: chromosome
studies, DNA studies, and biochemical genetic studies. Tests for cancer susceptibility
genes are usually done by DNA studies.
Chromosomes are the threadlike structures of DNA in every cell in our bodies that
contain our genes. Cytogenetics is a word used to describe the study of chromosomes.
The chromosomes need to be stained in order to see them with a microscope. When stained,
the chromosomes look like strings with light and dark bands.
A picture (an actual photograph from one cell) of all 46 chromosomes, in their pairs,
is called a karyotype. A normal female karyotype is written 46, XX, and a normal male
karyotype is written 46, XY.
The standard analysis of the chromosomal material evaluates both the number and structure
of the chromosomes, with an accuracy of over 99.9%. Chromosome analyses are usually
done using a blood sample, prenatal specimen, skin biopsy, or other tissue sample.
Chromosomes are analyzed by specially trained healthcare staff that have advanced
degrees in cytogenetic technology and genetics.
Chromosome studies may be done when a child is born with multiple birth defects. Chromosome
studies may also be done when people have certain types of leukemias and lymphomas,
to look for specific changes in the order of the chromosome material linked with these
types of cancers.
A gene is a section of DNA on a chromosome. The stretch of DNA is a code, or recipe,
for making a specific protein the body needs to function properly. To study genes,
you have to analyze the DNA to determine whether the DNA "alphabet" has any "spelling
errors" in it. There are two ways to analyze the DNA:
Direct DNA studies
Direct DNA studies simply look directly at the gene in question for an error. This
technology is called FISH or PCR. Errors in the DNA may include a replication of the
gene's DNA (duplication), a loss of a piece of the gene's DNA (deletion), a change
in a single unit (called a base pair) of the gene's DNA (point mutation), or the repeated
replication of a small sequence (for instance, 3 base pairs) of the gene's DNA (trinucleotide
repeat). Different types of errors or mutations are found in different disorders.
It is usually very important to find the mutation that is present in a family by first
studying the family member with the genetic disorder (in this case, cancer) before
testing other relatives without the cancer. When a particular mutation is found in
a relative with cancer, other family members can choose to have testing for the mutation
to determine if they have an increased risk to develop certain cancers and pass the
mutation on to the next generation. The DNA needed for direct DNA studies is usually
obtained by taking a blood sample.
Indirect DNA studies
Sometimes, the gene that causes a condition (when mutated) has not yet been identified,
but researchers know approximately where it lies on a particular chromosome. Or other
times, the gene is identified, but direct gene studies are not possible because the
gene is too large to analyze. In these cases, indirect DNA studies may be done. Indirect
DNA studies involve using markers to find out whether a person has inherited the crucial
region of the genetic code that is passing through the family with the disease. Markers
are DNA sequences located close to or even within the gene of interest. Because the
markers are so close, they are almost always inherited together with the disease.
When markers are this close to a gene, they are said to be linked. If someone in a
family has the same set of linked markers as the relative with the disease, this person
often also has the disease-causing gene mutation. Because indirect DNA studies involve
using linked markers, these types of studies are also called linkage studies.
Indirect studies usually involve blood samples from several family members, including
those with and without the disorder in question. This is to establish what pattern
of markers appear to be associated with the disease. Once the disease-associated pattern
of markers is identified, it is possible to offer testing to relatives to determine
who inherited this pattern, and as such, is at increased risk of cancer.
The accuracy of linkage studies depends on how close the markers are to the faulty
gene. In some cases, a reliable marker is not available and the test, therefore, cannot
give any useful information to the healthy family members. In many cases, several
family members are needed to establish the most accurate set of markers to determine
who is at risk for the disease in the family. Linkage studies may take many weeks
to complete because of the complexity of these studies.
Many of the cancer susceptibility genes that we know about today were discovered using
linkage studies of families who had multiple family members with cancer.
Biochemical genetic studies
Biochemical genetic testing involves the study of enzymes in the body that may be
abnormal in some way. Enzymes are proteins that regulate chemical reactions in the
body. The enzymes may be deficient or absent, unstable, or have altered activity that
can lead to signs in an adult or child (for example, birth defects). There are hundreds
of enzyme defects that can be studied in humans. Sometimes, rather than studying the
gene mutation that is causing the enzyme to be defective in the first place, it is
easier to study the enzyme itself (the gene product). The approach depends on the
disorder. Biochemical genetic studies may be done from a blood sample, urine sample,
spinal fluid, or other tissue sample, depending on the disorder.
Protein truncation studies
Another way to look at gene products, rather than the gene itself, is through protein
truncation studies. Testing involves looking at the protein a gene makes to see if
it is shorter than normal. Sometimes a mutation in a gene causes it to make a protein
that is truncated (shortened). With the protein truncation test, it is possible to
"measure" the length of the protein the gene is making to see if it is the right size
or shortened. Protein truncation studies can be performed on a blood sample. These
types of studies are often performed for disorders in which the known mutations most
often lead to shortened proteins.