By decoding some 40,000 genes in the human body, the Human Genome Project opened up an entirely new spectrum of knowledge. Genetic testing gives you the ability to understand your body's vulnerabilities, your unique genetic predispositions. Genetics is playing an increasingly important role in the diagnosis, monitoring, and treatment of diseases.
A genetic test looks at your individual DNA, the genetic information contained inside your cells. The test can often determine if you have a pre-disposition to develop a certain disease or could pass a disease onto your offspring.
In the April 2009 issue of Discover Magazine, journalist David Duncan investigated his genetic code.
“In essence I am aiming to answer two big, personal questions: How healthy am I at the very deepest level? And what can the seemingly endless profusion of new high-tech tests for various diseases and traits tell me about my health now and in the future?”
For the article, Duncan wanted specifically to gauge how well he could excrete the mercury in fish he eats. He discovered he is among the minority of people who carry a genetic mutation that apparently causes their cells to retain mercury for far longer - up to 190 days - greatly increasing the chance for cellular damage.
“Unfortunately, eliminating the source isn't possible for most other pollutants that we breathe, eat, drink, and absorb through our skin whether we want to or not, including man-made chemicals such as phthalates and perfluoro-octanoic acids, which are found in Teflon and other widespread products. The basic chemistry of these and thousands of other manufactured compounds incorporated in everyday products do not appear in nature; they have entered our environment so recently that our genes, cells, brains, and bodies have not yet evolved mechanisms for coping with them.”
|Deoxyribonucleic acid (DNA) is a long molecule made up of two strands of genetic material coiled around each other in a double helix structure.
DNA is found in the nucleus (center) of most cells. DNA is made up of 3 billion base pairs with a myriad of sequences of four nucleotides, chemicals represented as A. T, G, and C. These form the “instruction book” for a human being.
The four chemicals occur as pairs because a base on one strand is bound to a corresponding base on the other strand. When the bases are out of order, or missing, our cells often do not produce important proteins which can lead to a genetic disorder.
Common variants are called SNPs. For example, a SNP might change the DNA sequence from AAGGCTTA to ATGGCTAA
Not every gene is functioning all of the time. Some genes are turned on during critical points in development and then remain silent for the rest of our lives. Other genes remain active all of our lives so that our cells can produce important proteins that help us live - digest food, fight off the common cold, etc.
Some genetic compositions may make a person more susceptible to certain types of illness. For example, in 1994 and 1995 respectively, two variant (or mutant) genes were identified. BRCA1 and BRCA2 were found to predispose women to breast and ovarian cancers. The gene variant NAT2 may predispose some individuals to colon cancer. But not everyone with these gene variants gets cancer, why?
Environmental factors can turn genes on and off. Science is finding that the interplay of the environmental toxicology and genetics makes us who we are and often determines whether we are healthy or sick.
For example, we know that your odds of coming down with lung cancer greatly increase if you smoke. Farmers who apply certain pesticides to farm fields are twice as likely to contract melanoma, a deadly form of skin cancer. If you took synthetic HRT – hormone replacement therapy – you have an increased chance of heart disease, breast cancer, and ovarian cancer.
“Recent increases in chronic diseases like childhood asthma and autism cannot be due to major shifts in the human gene pool,” says physician and geneticist Francis Collins, former director of the National Human Genome Research Institute. While acknowledging that changes in diagnostic criteria and heightened awareness may play a role, Dr. Collins says that much of the increase “must be due to changes in the environment, which may produce disease in genetically predisposed persons.”
There is the science of genetics, and there is the science of epigenetics. We cannot change the genes we have – that's genetics, but we can change environmental factors in our life that may determine whether or not a gene is likely to manifest a disease – that's epigenetics.
Genetic testing can sample the risk for about 1500 diseases. Having a genetic marker for a disease is not a guarantee that you will absolutely get that disease with very few exceptions such as Huntington's disease, Muscular dystrophy, Tay Sachs, and cystic fibrosis. Most genetic markers, such as BRCA1 and BRCA2, merely point to an increased risk of developing a chronic disease in the future.
Imagine your genetic makeup as cards in a hand of poker. Predicting whether you will develop high blood pressure by testing a handful of genetic variants is like trying to guess whether you will win the hand by looking at just one card. A hand with an ace of clubs is statistically more likely to win than a hand with a six of clubs, but it depends on your other cards. And of course your genome is much more complicated. Genes interact in complex ways that are still not understood.
Family history is an important component of understanding one's potential genetic risk and this is still the best place to begin any genetic assessment. Yet family history alone does not reveal all risks. Most diseases are multifactorial, meaning a combination of genetic and environmental factors. Sometimes genetics are the stronger factor, but more often environmental influences are stronger.
More than 99% of human DNA sequences are exactly the same with every person. Variations in the remaining 1% or so can have a major impact on how any of us responds to disease.
Over the centuries, mutations or variants got introduced into the human DNA sequence. When a large number of people share the same variant, it is known as a single nucleotide polymorphism, or SNP (pronounced “snip.”)
The list of a person's SNPs constitutes a unique DNA pattern – a genetic fingerprint. It is a unique blueprint, giving instructions for a person's physical traits, such as eye color, hair texture, height, and susceptibility to disease.
SNPs make up about 90% of all human genetic variation. SNPs are also evolutionarily stable, not changing much from generation to generation, and this makes them easy to follow in population studies.
A catalogue of SNPs, or human variations, was released in 2005. It is called the HapMap. By comparing SNPs in patients with a disease to SNPs in the HapMap, scientists can pinpoint SNPs that are unique to that disease.
According to the Human Genome Project:
“SNPs do not cause disease, but they can help determine the likelihood that someone will develop a particular illness. One of the genes associated with Alzheimer's disease, apolipoprotein E or ApoE
, is a good example of how SNPs affect disease development. ApoE
contains two SNPs that result in three possible alleles for this gene: E2, E3, and E4. Each allele differs by one DNA base, and the protein product of each gene differs by one amino acid.
“Each individual inherits one maternal copy of ApoE
and one paternal copy of ApoE
. Research has shown that a person who inherits at least one E4 allele
will have a greater chance of developing Alzheimer's disease. Apparently, the change of one amino acid in the E4 protein alters its structure and function enough to make disease development more likely. Inheriting the E2 allele, on the other hand, seems to indicate that a person is less likely to develop Alzheimer's.
“Of course, SNPs are not absolute indicators of disease development. Someone who has inherited two E4 alleles may never develop Alzheimer's disease, while another who has inherited two E2 alleles may. ApoE
is just one gene that has been linked to Alzheimer's. Like most common chronic disorders such as heart disease, diabetes, or cancer, Alzheimer's is a disease that can be caused by variations in several genes. The polygenic nature of these disorders is what makes genetic testing for them so complicated.”
For example, the most common form of dwarfism, called achondroplasia, occurs because of a single base pair substitution, creating a mutation in the FGFR3 gene. The FGFR3 gene provides instructions for making a protein involved in the development and maintenance of bone and brain tissue. Researchers believe that the mutation causes the protein to be overly active, which causes the disturbances in bone growth seen with this disorder. One copy of the altered gene in each cell is sufficient to cause the disorder. About 80 percent of people with achondroplasia have average-size parents; these cases result from a new mutation in the FGFR3 gene. In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents. Individuals who inherit two altered copies of this gene typically have very severe problems with bone growth, and are usually stillborn or die shortly after birth from respiratory failure.
Other genetic diseases are caused by different SNPs that may occur anywhere along the length of a gene. For example, cystic fibrosis (CF), a common genetic disease in the Caucasian population, is caused by over hundreds of different mutations along the gene. Two altered genes must be present for CF to appear. This means that if both parents are CF carriers, their offspring would only express CF symptoms if they had inherited one defective copy of the CFTR gene from each parent.
Genetics versus Epigenetics – the Environmental Influence
About 13 percent of Americans over the age of 65 have Alzheimer's and half of those over age 85 will develop Alzheimer's or a closely related dementia, according to current statistics. The World Health Organization estimates that there are 18 million people worldwide with Alzheimer's disease, a figure projected to nearly double to 34 million by 2025. Although some cases appear to be inherited in what is called an autosomal dominant pattern, many other cases appear to first time expressions of the disease – no prior family history. Conventional wisdom says as much as 80% of the disease is attributable to genetics. But not all agree.
We did not have an epidemic of Alzheimer's disease 100, 200 years ago, why? Did people not live long enough? Was it not recognized or recorded? Has there been, as many suggest, a modern day explosion of it like cancer, diabetes, and so many other chronic illnesses? Is MSG a factor? How about vitamin K or B12 deficiencies? Severe hypothyroidism? Perhaps exposure to the neurotoxin aluminum from aluminum foil, aluminum cookware, common table salt, processed cheeses, refined flours, baking powders, contaminated water, deodorants, cigarette filters, beer, pesticides, and over-the-counter drugs such as antacids, anti-diarrhea drugs and drugs used for pain and inflammation?
The picture is fuzzy yet about environmental connections to Alzheimer's. But not so with obesity.
Paula Baillie-Hamilton, a doctor at Stirling University in Scotland, observed in The Journal of Alternative and Complementary Medicine in 2002 that obesity rates had risen in lockstep with the use of chemicals such as pesticides and plasticizers over the previous 40 years and thus, there might be a connection. It was a novel idea at the time to mainstream medicine. Since then, evidence has been steadily accumulating. For example, we determined how the plastic chemicals bisphenol A (BPA) and phthalates create fat cells. We now know that certain hormone-mimicking pollutants, ubiquitous in the food chain, have two previously unsuspected effects:
• These chemicals act on genes in the developing fetus and newborn to turn more precursor cells into fat cells, which stay with you for life.
• They may alter metabolic rate, so that the body hoards calories rather than burning them.
Prescription drugs can also act as environmental pollutants. For example, one of the side effects of two popular diabetes drugs (generic names – rosiglitazone and pioglitazone) is obesity. The drugs activate a receptor called PPAR gamma, which acts like a switch for cells' fate: in one position it allows cells to remain fibroblasts (cells that become connective tissue), in another it prompts them to become adipocytes – fat cells. The drugs push the switch in the “become a fat cell” direction.
And who can forget the lessons of the “Super Size Me” movie? We have greatly increased the calories, trans fats, and insulin-spiking content of our foods.
On the genetic front, a mind-numbingly complex array of genes influence body weight. By sampling fat tissue, one group of researchers recently found that the activity of 17,000 genes correlate with body mass index (a measure of body fat based on height and weight), and 14,900 correlate with waist-to-hip ratio. Complicating matters further, these genes seem to operate in large networks, interacting with each other and the environment to influence weight.
When it comes to obesity, it appears that food ranks as the number one contributor to the problem, chemical pollutants rank second, and genetics comes in a more distant third.
Genetic disease results from a variation, or mutation, in a chromosome or in one or several base pairs on a gene. Some mutations are inherited, most occur spontaneously. For many of the adult onset diseases, genetic mutations can occur over the lifetime of the individual while the cells are making copies of themselves or dividing. Environmental effects such as radiation, chemicals, and lack of nutrient-dense food play a role in these mutations.
Studies of identical twins show just how much environmental influences trump genetics. Identical twins, siblings who share the same genome, do not always develop the same DNA-related health conditions.
Genetic Testing as Preventive Medicine
Would you toss out your aluminum cookware and your MSG “flavor enhanced” food if you knew your genetic makeup could make Alzheimer's disease more likely in your future? Would you take a folic acid supplement if you thought Alzheimer's, heart disease, or pregnancy was in your future?
Most people want a genetic test to provide insight, to empower them to take precautionary steps. DNA knowledge is a starting point. Knowing which risks you have inherited can help guide your health prevention strategies. You can assess your environment and lifestyle and take important steps to protect your health in the future.
Kári Stefánsson, the famous gene hunter who spearheaded the effort that mapped 65 percent of Iceland's genome, said:
“There's a paradigm shift from intervention to preventive medicine as we speak. It happened when people started to download information about diseases. This didn't happen before. Doctors used to be omnipotent; no one ever questioned them.”
People increasingly are looking for answers that mainstream medicine rarely gives them – how to prevent disease.
Keep in mind that the science of genetic testing is still new, and it is not a perfect or complete science. It was only in 2003 that the Human Genome Project finished mapping the entire human genetic makeup. Five years later, an editorial in the New England Journal of Medicine cautioned:
“Even the ardent proponents of genomic susceptibility testing would agree that for most diseases, we are still at the early stages of identifying the full list of susceptibility-associated variants. …diabetes, various cancers, and heart disease are so-called complex diseases thought to be caused by multiple gene variants, interactions among these variants, and interactions between variants and environmental factors. Thus, a full accounting of disease susceptibility awaits the identification of these multiple variants and their interactions in well-designed studies. What we have now is recognition of a limited number of variants associated with relative risks of diseases on the order of 1.5 or lower.”
Not everyone agrees how strong the connection is between a gene variant and susceptibility to disease. And new discoveries still await us. In April, 2010, a newly-identified gene variant was dubbed MTHFD1L. It may make a person nearly twice as likely to inherit Alzheimer's disease. This gene is known to be involved in the metabolism of folate, which in turn influences the body's levels of homocysteine. High homocysteine levels, which happens when there is too little folate in the diet, have been shown to be a risk factor for Alzheimer's disease. This knowledge is now added to what we learned two decades ago about the ApoE gene which can increase risk for late-onset Alzheimer's disease.
Science is still shuffling its way through the genetic deck of cards.
The Politics of Knowledge
In 2008, Congress passed the Genetic Information Nondiscrimination Act (GINA), which prohibits employers and health insurance companies from denying jobs or coverage based on an individual's DNA. Advocates of the measure considered its protections crucial to the advance of medical research and personalized medicine, both of which rely increasingly on genetic testing.
“By removing the fear of discrimination, GINA may now allow people to engage in testing that will improve prevention and treatment,” said Joann Boughman, executive vice president of the American Society of Human Genetics. “Hopefully it will lead to a change in mind-set in medical practice.”
GINA was intended to address concerns about identifying potential genetic liabilities in otherwise healthy people. Yet studies have shown that some people avoid getting tested because they are afraid the results will somehow be used against them. And there is no clarity yet as to how the new health care reform bill of 2010, and its requirement for electronic recordkeeping, will play out. President Barack Obama said his administration wants every American to have an electronic health record by 2014, and more than $36 billion was allotted to the effort in a prior economic stimulus bill.
In 2002, under President George W. Bush, the right of a patient to control his most sensitive personal data - from prescriptions to DNA - was eliminated by federal regulators implementing the Health Insurance Portability and Accountability Act (HIPPA). Privacy notices you sign in doctors' offices do not actually give you any control over your personal data; they merely describe how the data will be used and disclosed. HIPAA says mainly that information will not be released to anyone without the patient's consent – with the notable exception that the government is not required to obtain the patient's consent, and may obtain that information at will. HIPAA applies only to practices which transmit information electronically. So those offices with paper charts who never receive or send information through the Internet, or who never do electronic billing, are theoretically not included in the HIPAA act.
Putting Genetic Testing To Work for Prevention
You can acquire some very useful information through genetic testing. For example, do you have the genes to efficiently use folic acid? Methylenetetrahydrofolate reductase (MTHFR) is a rare genetic variant that can lead to complications in pregnancy. Many people do not know that they have this variant gene until after they have had several unsuccessful pregnancies. A mother with the MTHFR variant gene is unable to efficiently metabolize folic acid, also known as vitamin B9; the disorder has been linked to a variety of pregnancy complications including Down syndrome and congenital malformations. This variant is also implicated in autism.
This same variant also plays a role in our adult lives. Those with it are prone to having elevated levels of homocysteine in their blood and that leads to problems with heart attacks, strokes, depression, cervical and uterine cancer, arthritis, spina bifida, and Alzheimer's.
Interaction between vitamin D and another common genetic variant alters the risk of developing multiple sclerosis (MS). We have long noticed that MS is more prevalent in the northern latitudes where there is less sunlight, therefore less vitamin D. In 2009, researchers at the University of Oxford and the University of British Columbia established a direct relationship between the gene variant DRB1*1501 and vitamin D. If too little of the vitamin is available, the gene may not function properly and the person is more likely to develop MS. Researchers hypothesize that the gene-environment interaction inhibits the thymus, a key component of the immune system, from performing its regular tasks.
"We have known for a long time that genes and environment determine MS risk," said Professor George Ebers, University of Oxford. He and his research colleagues believe that vitamin D deficiency in mothers or even in a previous generation may lead to altered expression of DRB1*1501 in offspring. "Epigenetics will have important implications, not only for MS, but for other common diseases. For mothers, taking care of their health during their reproductive years may have beneficial effects on the health of their future children or even grandchildren."
SNPs have been identified in the vicinity of the HNF1A gene that are strongly related to high levels of chronic inflammation. C-reactive protein (CRP) is one way to measure that; the higher your CRP, the more susceptible you appear to be to coronary heart disease.
SNPs have been indentified that could influence a myriad of health conditions ranging from osteoporosis to metabolic syndrome, from cancer to the ability to detoxify heavy metals – and much more.
Your genetic desk of cards cannot be changed. But you have more control than you might think over exactly how those cards play out. You can greatly influence the outcome in most cases by what you eat, what you breathe, how much radiation and electrosmog you are exposed to, how much nutrient-dense food you eat… understanding what optimum health really means and what you can do to achieve it, maintain it, and perhaps even influence the health of your grandchildren and great grandchildren.
Knowing from a genetic test that you're at risk allows you to pay closer attention to its warning signs, detect it earlier, and very possibly head off the worst case scenarios from that risk.
BBC's "Ghost in Your Genes" Video
And it's not just what is happening to our bodies today. It's what is happening to our genes that are passed down to our children and grandchildren for centuries to come. Look at how the science of inheritance is being turned on its head.