Studies for Single Gene Defects: DNA (Direct and Indirect)

What are the different studies for single gene defects?

Genes are made up of the chemical DNA. 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 markers 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 repeated piece of DNA such as a trinucleotide repeat, a missing piece of DNA (deletion), or an alteration in the DNA code (point mutation). Different types of errors or "mutations" are found in different disorders. It is important to first find which type of error is present in a family by studying the family member with the disorder in question. The results of the DNA test are then used to compare directly to other relatives in the family to determine who else has the disease or carries the gene for the disease (and is at risk to pass it on to the next generation). The DNA is usually obtained by taking a blood sample.

Indirect DNA studies

Sometimes, the error in the gene responsible for causing a disease has not been identified. In these cases, "markers" are used 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 the area of interest that are so close that they are almost always inherited together with the disease. When markers are this close to a gene where they are inherited together, they are said to be "linked." In this way, if someone has the set of linked markers, he or she will also have the disease-causing gene. For this reason, these types of studies are also called "linkage studies."

The family member with the disorder in question is studied first (as in direct DNA analysis). The pattern of the person's markers is compared to other relatives. If there is an exact match, then those relatives are also likely to have the faulty gene.

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.