Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
A gene is a short stretch 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: by direct studies (looking at the actual gene itself), or by indirect studies (looking at areas of DNA, called markers, that are very close to the gene).
Direct DNA studies
Direct DNA studies simply look directly at the gene in question for an error. 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), an alteration 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 studying the family member with the disorder in question (in this case, cancer), before testing 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 to 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 (when mutated) causes a condition 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.