Recently, Dr. Phil Farrell visited Promega Corporation to present his pioneering research to trace the origins of the most common mutation that causes cystic fibrosis. This mutation, ΔF508, results in a 3 bp deletion in human genomic DNA and a deletion of the phenylalanine residue at amino acid position 508 of the cystic fibrosis transmembrane conductance regulator protein. Dr. Farrell and the members of his lab at the University of Wisconsin School of Medicine and Public Health are examining ancient DNA to answer the question: Is there some protective effect of the ΔF508 mutation that would explain why the frequency of this mutation is so high (as high as 1/1,000 live births) in certain populations?
One hypothesis is that the ΔF508 mutation conveys protection against a disease that was common during prehistory, such as tuberculosis or cholera, similar to the protective effect afforded by sickle cell anemia-causing mutations against malaria. However, scientists have been unable to identify any protective effects of this mutation. Dr. Farrell and his team are taking a different approach. They know that skeletal remains from the Bronze and Iron Ages have relatively high levels of lead and arsenic, consistent with the manufacturing and use of metal tools of that era, and have developed the hypothesis that a single copy of the ΔF508 mutation conveys protection against metal toxicity. To strengthen their hypothesis, Dr. Farrell and his team are extracting DNA from teeth of preRoman, Roman and medieval Europeans skeletal remains and using PCR to detect the ΔF508 mutation and monitor its frequency in these populations.
One potential problem with these types of studies is contamination with modern DNA(1)
. For the data to be credible, the appropriate controls must be performed to detect such contamination and eliminate those samples from the analysis. In Dr. Farrell's lab, contamination is detected by including human-specific short tandem repeat (STR) primers along with the ΔF508-specific primers to detect the mutation and generate an STR profile in a single amplification, then comparing this STR profile to STR profiles of laboratory members.
To learn more about Dr. Farrell's research to detect the origins of the ΔF508 mutation and his use of STR technology to detect modern DNA contamination, view the video.