The Human Genome Project, completed in 2003, demonstrated humans have approximately 20,000 genes. How these genes interact with one another and respond to environmental factors goes a long way toward explaining a person's health history.
Genes are segments of DNA that are essentially recipes for the construction of proteins within the cells of our body. Most tissues have protein structures: Enzymes that facilitate metabolism are proteins, and chemical signaling networks that run the most basic functions of life are made of proteins.
The expression of genes is orchestrated by signals. Those signals are proteins that promote or inhibit the transcription of genes for the purpose of making other proteins. It is the timing of this gene expression and the combination of genes being expressed at any given time that determines the fate of a cell or the function the cell performs.
Genes typically come in different flavors, called alleles. That is, genes can have variants. Some variants are harmful, some neutral and others beneficial. All variants are mutations, but I will reserve this term for variants that are harmful.
Most variants of a gene are neutral. Each human is unique because of his or her unique combination of alleles. However, variances also explain why we have different susceptibilities to diseases, age differently and respond differently to environmental conditions and medications.
Genes are made up of a linear code. The code has words with three letters each. The letters are, in fact, molecules. Each word corresponds to one of the 20 kinds of amino acids that make up proteins. Mutations are misspellings of these words.
There are a variety of ways misspellings occur. Errors can occur in any text, especially a text being copied many times over, as is the case with DNA. There can be incorrect letters, extra letters and deleted letters, and sometimes whole segments are mistakenly copied multiple times.
Such DNA errors result in incorrect amino acid sequences when proteins are constructed. These can cause the protein to malfunction. Malfunctioning proteins give rise to many human ailments.
People suffering from cystic fibrosis have a number of challenging, life-threatening ailments. These include extremely labored breathing, infections, destruction of lung tissue, pancreatic cysts and inability to secrete digestive enzymes. The breathing difficulties arise from lungs that produce thick, sticky secretions.
In most cases a simple deletion of three letters in a gene, identified as CFTR, causes the problem. The deletion results in the loss of the 508th amino acid (phenylalanine) in a protein with 1,460 amino acids. Omission of these 3 letters out of the 3 billion in the entire human genome results in this devastating multi-organ disease.
The linkage between CF and this mutation was made in 1989. Among genetic disorders, it would seem CF is one of the least complex. However, we now know there are other mutations (more than 1,000) that can give rise to CF. We also know there are many other variants of genes classified as modifiers that affect the severity of CF.
There are other single mutations that are strongly linked to diseases. Women who have a BRACA1 mutation are predisposed to a high risk of breast and ovarian cancer.
More often one's predisposition to develop a certain condition depends on a variety of factors. Usually, there are a suite of genes contributing to one's overall risk. One's aggregate risk is compounded by the risk associated with each mutation. One gene may enhance a person's risk 10 percent, another 20 percent, and a third 8 percent.
Importantly, environmental factors play a significant role. These can include such things as air quality, cigarette smoking, obesity and stress. Those with elevated risk factors for type 2 diabetes will want to reduce their risk by modifying their diets and avoiding becoming overweight.
This highlights an important point about how we decide to use this new knowledge about our personal genetic makeup. It won't be long before the cost of having your personal genome decoded will be affordable. What would be your reasons for knowing the make-up of your DNA?
In the revealing book "The Language of Life -- DNA and the Revolution in Personalized Medicine," Dr. Francis S. Collins suggests a straightforward way of looking at this question. He proposes one's desire to know should be weighted by three factors.
First, what is the risk (R) that one has the disorder? To evaluate this it is important to distinguish relative risk and absolute risk. I recommend to you Dr. Collins's book to sort this out for each disease one wants to consider.
Second, what is the burden (B) of the disease? That is, how severe, life-threatening or lifestyle-altering is the disease? A skin disorder like eczema is a nuisance for most who have it, but isn't life-threatening. Diabetes, cancer, heart attack are clearly life-threatening. There are many shades of gray in between these examples.
Finally, what interventions (I) are possible? Where preventive strategies like diet and smoking cessation are effective, intervention is critical. Likewise, early detection can be important and can have significant impact on the success of therapy. Such is the case in breast cancer. So, screening and effective therapies play a role.
We are on the cusp of a revolution in medicine. The Human Genome Project has jump-started whole new strategies for preventing and treating disease. Further research is expected to demonstrate other linkages between genetic mutations and diseases. These will lead the way to further progress in prevention and treatment strategies.
To achieve these goals, more extensive databases must be developed. It would be desirable to have as complete a record as possible of people's family and personal health history stored in electronic medical records. This would necessitate genetic testing of as many people as possible, but especially those suffering from diseases with suspected genetic origins.
This won't be easy. It will require protections against unauthorized use of personal health data. Data should be stored anonymously in such a way that it can only be used to search for patterns between genetic variations and diseases. It will also require protections against discrimination against those with predispositions to certain diseases.
The rewards of exploiting this newfound knowledge are too great for us to be put off by the risks. We must find ways to collect the data, do the research and protect individuals who want to contribute their genetic and family histories to the data pool or discover their susceptibility to diseases that threaten them.
Steve Luckstead is a medical physicist in the radiation oncology department at St. Mary Medical Center. He can be reached at firstname.lastname@example.org.