Chromosome 17 and BRCA1
Among the most common diseases affecting the female population, breast cancer develops in one of every eight American women. This means that almost 200,000 women suffer from the disease each year. Doctors would advise women to take necessary precautions, such as routine surveillance, in order to ensure a life without obtaining this disease prior to understanding any genetic linkage of breast cancer. Although many external factors contribute to breast cancer, current investigations reveal that five to ten percent of these cases may be attributed to genetic inheritance (Lynch, 1999). This knowledge, an ingenious finding by Mary-Claire King in 1990, linked breast cancer to the long-arm of chromosome 17 (Biesecker, 1997). Since the discovery of possible genetic linkage, doctors have been able to delineate those individuals who are most prone to the disorder, and immediately, these women begin to act in accordance with doctor’s suggestions to reduce their risk (Rosenthal et. al., 1999).
Mary-Claire King not only determined that breast cancer was a genetic disorder, her findings also suggest that the mutation of gene BRCA1 (Breast Cancer one) is responsible for most inherited breast cancer. Further investigations pointed to another gene, BRCA2, as also contributing to genetic inheritance. Unlike BRCA1, BRCA2 is found on chromosome 13. Researchers have found that 90% of all inherited cases of breast cancer may be due to mutations of these individual genes (Lynch et. al., 1999).
The BRCA1 gene has the locus designation, 17q21, and is responsible for this autosomal dominant syndrome (Merajver et. al., 1995). This tumor suppressor gene, contains 23 exons, each ranging from 41 to 311 base pairs. Point mutations or small insertions and deletions cause the disruption of BRCA1 from its normal function, which then in turn promotes the onset of breast cancer (Puget et. al., 1999). Various methods of positional cloning have been used to detect mutations of BRCA1, but originally the gene was isolated using single-strand conformation polymorphism (SSCP) and direct sequencing. During 1994, when the gene was first discovered, SSCP was done using both genomic DNA and cDNA from lymphoblast RNA (Friedman, et. al, 1994). SSCP analysis detected each variant and sequenced it on several templates. Results from this experiment helped prove the involvement of BRCA1 to breast cancer development. Other studies have used Southern Blotting techniques and other Polymerase Chain Reaction (PCR) methods in order to further analyze BRCA1.
BRCA1 encodes a protein that is approximately 1865 amino acids in length, which is "a tumor suppressor, a protein that acts as a...