What is the genome? DNA is the template that serves as the code for the cells to manufacture the proteins that make up our bodies and carry out metabolic functions. DNA is made up of 4 nucleotide bases (adenine, thymine, cytosine, and guanine) arranged into a particular order. The sequence of bases on one strand of DNA is complementary to the sequence of bases on the other strand of DNA (adenine matches with thymine and cytosine matches with guanine). DNA is a double strand of long strings of these bases twisted into a spiral (the double helix) and called a chromosome. Our cells have 46 chromosomes – half of which are inherited from the father and half from the mother.
Nucleotide bases are organized linearly into strands of DNA, and their order serves as a code to tell the body which proteins to make, or which genes to turn on and off, much like the letters on this page serve as a code to convey information to you because of the order in which the letters are arranged. Think of the letters as nucleotide bases and the words as genes. The sequence of nucleotides in a gene is read and translated by a cell to produce a chain of amino acids which then folds into a 3-dimensional protein. The order of the amino acids in a protein corresponds to the order of nucleotides in the gene – this relationship is called the genetic code. This code is ultimately responsible for the function of the final protein. A change in a nucleotide, called a mutation, causes a change in the final protein, which can render the protein ineffective or even dangerous, much like a change in one word of a sentence can alter the entire meaning of the sentence.
There are 6 billion base pairs of DNA in the human genome, arranged into 22,000 genes, which code for all of the proteins made in the body. There is also genetic material between the genes that regulates gene expression – so that even though all of your cells contain 46 chromosomes, not all of the genes are turned on in all of the cells. The protein-coding genes (exome) make up 1.4% of the total genetic material, and it is these genes that are best understood, and mutations within these genes that cause disease.
We differ from each other because of variations in the sequence of our DNA. Variants can be caused by the substitution of one base for another, called single-nucleotide-polymorphisms or SNPs. Sometimes changes in a nucleotide can cause truncation of the final code so that a protein is not produced at all. There are also a variety of insertions, deletions, inversions, and translocations that affect not only our appearance, but even whether or not we survive to full term birth, or whether or not we can have children.
How is your genome tested?
The human genome was first sequenced in 2004 (rough draft in 2001) in a project called The Human Genome Project, led by Dr. Craig Venter, taking over 10 years, 2000 researchers, and over a billion dollars. The final sequence obtained in this project is referred to as the reference genome, approximately 3 billion base pairs in length, with still some remaining gaps which occur in regions of the genome that are difficult to sequence with current technology, or that are highly variable among individuals.
Current technology, called high-throughput DNA sequencing, or Next Generation Sequencing, allows for much more rapid sequencing of a genome (days to weeks) by breaking up the DNA strands into short fragments (100-base-pairs), then assembling these “reads” by computer into longer continuous sequences based on information from fragment overlaps and comparison to the reference genome. These methods have about a 1% error rate, so in order to ensure accuracy, each base is typically sequenced a minimum of 30 times (30x) – this is called sequencing depth. In order to lower the error rate, labs must increase the sequencing depth – so that when we find a variation with clinical significance, we can be sure that the information is correct, rather than reporting information that is not reliable. The higher the sequencing depth, the more correct the results will be. For clinical purposes, sequencing depth of 100-120x is much more trustworthy than just 30x.
High-throughput DNA Sequencing has allowed us to sequence both the entire genome (whole genome sequencing) and the exome (the protein-coding genes) at a much lower cost than just 10 years ago. The exome seems to be much more clinically relevant than the whole genome, at our current level of understanding, and given that the exome represents only about 1% of the genome, we can sequence the clinically relevant exome at a much greater depth than the whole genome, giving us trustworthy information that is backed up by increasing amounts of research data.
Here’s a helpful comparison – you could have your whole genome sequenced at 20-30x for a cost of $10,000-$20,000, or you could have your whole exome sequenced at a much more trustworthy depth of up to 120x for $3000-$10,000, giving you clinical information that you can trust and use to improve your health. Eventually researchers will better understand the non-protein coding genetic material, however, at this point it may make more sense to focus on understanding your exome, so that you can make changes to your lifestyle now to lower your future health risk, rather than wait 30 years until the non-protein coding regions of the genome are better understood.
Can you use this information to improve your health?
Absolutely! You can learn if you are at risk of serious medical conditions such as heart disease, diabetes, and cancer, how to best tailor your diet, exercise, and lifestyle choices to optimize your health, and which medications and therapies are safest and most effective for you. Specific genetic information can direct the type of screening a patient receives, meaning that certain cancers can be caught earlier and be easier to treat. We check for genetic risks for heart dysrhythmias, structural heart disease, and coronary artery disease. We have identified many rare disease in patients, which can explain symptoms that have been confusing to you. Knowing that you have a rare condition can help your doctors to better manage your symptoms, provide more effective mitigation therapies, and create a surveillance plan against the disease’s most significant effects. Sometimes knowing that a condition you have developed has a genetic basis can lift the guilt you may feel, thinking that you had done something wrong to cause the disease. Many people are concerned about their risk for developing dementia as they age – if you are at higher genetic risk, much of the risk can be mitigated by taking aggressive lifestyle and nutritional supplementation steps now in order to markedly lower your future risk. We also analyze the genes responsible for metabolizing many medications, so that we can predict which medications will work well and which will not in certain situations.
Have you ever wondered why certain diets work better for some people than others? There is exciting research going on right now that compares how people perform on different diets based on variations in their DNA. We have used these studies to recommend specific diets for people. A few options include the saturated fat diet (similar to Atkins); the monounsaturated fat diet (Mediterranean diet); and the high carbohydrate, low-fat diet. We can also show you how different exercises affect your body in unique ways. For instance, we have results that say aerobic exercise may be more or less likely to improve your insulin sensitivity or more or less likely to improve your good cholesterol. We can also show you which types of athletic activities in which you are more genetically suited to excel.
Most people carry multiple diseases in their DNA that they do not express – such diseases are called “recessive” and are not problems unless the person and their partner both carry the same recessive disease; in that case, the couple’s children are at risk of becoming afflicted with that disease. We can help you to understand which recessive traits you carry, which could be important as you consider having children.
Ancestry determination is also included with our analysis. We compare your DNA with 52 different populations from around the globe. Which region of the world do your ancestors come from?
Genomics is such an exciting and cutting-edge area of medicine – as research progresses, we will have even more tools at our disposal to improve our health and the health of our children! Let me invite you to jump in to a deeper understanding of the miracle of your body, and give you more tools to take good care of this precious gift.
Learn More about Our New Genome Testing Program.