We've all had our blood drawn or our throats swabbed to test for certain diseases. But have you ever had your entire genome - all 3.1 billion nucleotides - sequenced to determine your risk for potentially life-threatening illnesses?
Researchers at the Hopkins Kimmel Cancer Center have sequenced the genome of a patient with a family history of pancreatic cancer. They were able to identify a gene that increases susceptibility to pancreatic cancer by comparing the patient's DNA sequence with that of normal individuals.
This is one of the first times "personalized" genome sequencing has been used to help individual patients, and as the costs of sequencing continue to decrease, the technique is likely to become ever more prevalent.
"In our past experience with familial predisposition to cancer, the patient most commonly inherits one mutant copy of a gene at birth and the second copy is inactivated in the cancer, the so called 'second hit,'" James Eshleman from the Department of Oncology said.
To find the inherited mutant copy of the gene, researchers looked for bases that would make the mutant protein shorter than the normal copy. Proteins are made up of amino acids, and each amino acid corresponds to a three-base sequence in the DNA.
However, some three-base sequences, called codons, don't actually match up with an amino acid, but instead signal for the growing amino acid chain to be broken off to form the protein.
In the patient with the pancreatic cancer predisposition, researchers combed his exome, or the portions of his DNA that code for proteins. They found that there were 15,000 total bases that varied with the consensus human genome. Most of these bases code for traits for which you would expect variation, such as eye color, skin tone, etc. Only about 200 of those mutations resulted in truncated proteins.
But to narrow down the suspect pool for a potential pancreatic cancer gene even more, researchers searched for the "second hit" - the second copy of a gene that is inactivated when a person develops cancer - and were finally able to shrink the field down to three possible genes.
The most suspicious of the three was PALB2, since it is associated with another gene BRCA2, known as the predisposition gene for breast, ovarian and pancreatic cancers.
To verify that this gene increases cancer susceptibility, the researchers studied 96 more individuals, and three were found to have mutations in the same gene. In a large control group with no history of pancreatic cancer, mutations in PALB2 were not found. Although a test for this gene is not currently available, scientists hope that these results can be used to develop one.
"This would allow increased cancer surveillance for early signs of disease in those at risk," Sian Jones, at the Hopkins Center for Cancer Genetics and the lead researcher in this study, said. "We also expect that this approach for identifying susceptibility genes will be extended to discover not only more cancer-causing genes, but also those responsible for other hereditary diseases."
Broadening the use of this technology to other types of cancers would have enormous ramifications for the future of preventative medicine.
"Thanks to improvements in DNA technology, the complete sequencing of human exomes and genome is accelerating," Michael Goggins at the Hopkins Pancreatic Cancer Research Center said. "As the exome of more and more individuals are sequenced in the coming years, our understanding of DNA sequence variants is likely to increase greatly and will allow investigators to rapidly identify the genetic basis of many human diseases."
