Individuals of Ashkenazi Jewish descent are at higher than normal risk for breas
ID: 44120 • Letter: I
Question
Individuals of Ashkenazi Jewish descent are at higher than normal risk for breast cancer due to three different mutations that are common in that population. For example, women with a certain mutation in the gene BRCA1 have an 85% lifetime risk of developing breast cancer and 45% lifetime risk of developing ovarian cancer, compared with 12% and 5%, respectively, for women who do not carry a BRCA1 or BRCA2 mutation. If you are Ashkenazi Jewish and ask for genetic testing to evaluate your risk of getting breast cancer, you will likely be genotyped for just the 3 mutations {BRCA1 185delAG, BRCA1 5382insC and BRCA2 6174delT) that are common in Ashkenazi Jews. A genetic testing company routinely does genetic testing for these mutations using an allele-specific hybridization technique. Here are some sample results:
(1) There are lots of other mutations in BRCA1 and BRCA2 that can cause an increased risk of developing cancer. If the genes were sequenced you would know if you had any of them, whereas this assay just looks for 3 specific mutations. Why, then, do we not sequence everyone? (2) Explain the principle behind the genotyping assay shown here. (3) Interpret the results for each individual tested.
Explanation / Answer
1. Squencing each mutation requires more gene and it is more time taking, Practically it is very difficult to scan for all the mutaions that a person have that increases their risk of getting breast cancer. In mst if he cases, people are generally scanned fo rht epresence of selected mutaions such as BRC1 and BRC2.
2. An allele-specific oligonucleotide (ASO) is a short piece of synthetic DNA complementary to the sequence of a variable target DNA. This synthetic DNA act as a probe for the selected target, which can be marked by using southern blot assay or simple dot assay.If the test genome is ontaining the selective target, the probe binds to the site and appears as a spot in the assay. This methos is widely used in genetic testing, forensics an in research of molecular biology.
3. Subject 1 has no risk of developing breast cancer. Subect 2 and subect 3 has equal risks of developing breast cancer.