Personal Genetics Education Project

What is Personal Genetics?

Personal genome sequencing assesses the status of all of your genes at one time, just as if the Human Genome Project were conducted specifically on you.

This assessment would include genes that are implicated in causing disease, in ancestry, in physical traits,  but also genes that are not yet well understood, and other parts of your genetic makeup that may have some influence on your health and other characteristics. As its stands today, only the information from the parts of your genome that are well understood might benefit your present health care choices. However, as more and more people are sequenced, scientists will be provided with a larger set of data from which to learn about the poorly understood regions of the genome and their functions, including relationships to diseases. This is one potential benefit to health care consumers in the future (see Genotype and phenotype). In some ways, widespread personal genome sequencing may blur the line between medical practice and biomedical research.

The completion of the Human Genome Project was a great advance for medical research, providing us with part of the blueprint that makes us human. However, the DNA sequence produced by the Human Genome Project is not identical to yours; virtually every individual on the planet carries a unique set of variations in their DNA sequence, affecting their outward appearance, their behavior, and from a medical standpoint, their susceptibility to disease. Today, more and more people are being genetically tested for known genetic mutations that are thought to be associated with specific diseases.  Genetic tests usually characterize only one gene (or just specific parts of one gene),and the availability of such genetic tests depends on the ability of scientists to link well-characterized diseases to particular genes. For conditions with specific genetic causes, such as Huntington’s disease or cystic fibrosis, these tests have proven to be relatively straightforward. In contrast, progress has been more challenging with respect to complex and multifactorial diseases, such as cancer.

Ultimately, the application of genomic information could enhance our ability to make informed and appropriate decisions regarding health care, including, for example, the treatment of specific diseases or predispositions and the choice of drugs and drug dosage. At the same time, the questions it raises, and the possible unforeseen medical and social consequences, are yet to be fully explored. This advent of “personal genetics” will bring novel challenges and extensive questions on the ethical, legal and social issues (ELSI) that we, as a society and as individuals, need to address.

How might personal genetics impact medicine and health care?

Currently, having your genome sequenced would be similar to having thousands of genetic tests done at the same time – you would learn quite a bit about your genetic make-up, but the information that would be gleaned from your sequence would be limited to the parts of the genome that are already well understood. However, if many people have their DNA sequenced and provide their medical history as well as a detailed physical description of themselves, personal genome sequencing could be a powerful tool for learning more about the parts of the genome that are poorly understood.

Essentially, the power of sequencing comes from the exercise of comparing genotype and phenotype; by analyzing the genomic sequences (genotypes) and physical characteristics (phenotypes) of millions of people, personal genome sequencing has the potential to link specific traits to specific genes. The most obvious benefit of these analyses will be to better understand the interplay of nature and nurture in known diseases, with the hope that they would lead to better treatments, cures, preventative measures, and healthier generations of children.

Notably, the field of pharmacogenomics is one area where there have already been many successes.  Our DNA can impact how we respond to drugs, which can help people decide what sorts of drugs are best for them, and also how we metabolize certain drugs also has a genetic component.

Recently, there have been several examples where genome sequencing has resulted in both a diagnosis and treatment plan of a patient.  ”One in a billlion: A boy’s life, a medicial mystery“, written by Mark Gallagher and Katherine Gallagher, describes many of the scientific and personal issues that underlie the emerging field of medical sequencing.

Physicians and personal genomes

Doctors will be faced with many questions as personal genome sequencing drops in cost and interest in genetics increases. Furthermore, a recent study conducted in the United States shows that a large majority of the population is willing to participate in studies about genes, the environment, and health.

In this time when the promises of personalized medicine outpace some of the realities in the clinic, physicians will increasingly be managing expectations of patients and interpreting the latest scientific discoveries and policy guidelines issued from insurers.

pgEd is in the process of developing a short list of papers that we hope will give doctors and other medical professionals a baseline understanding of the issues and serve as a jumping off point for more in depth reading. We also recommend the Genetics and Genomics for Health Professionals resource created by the NHGRI.  resources that have been created at the Beth Israel Deaconess Medical Center’s Genomic Medicine Initiative.  Dr. Eric Topol’s excellent book, The Creative Destruction of Medicine, is another resource pgEd recommends for healthcare workers and anyone who is interested in a look at how technology , and an embrace of the changes innovation can bring, could transform health and the healthcare community.

What is genotype? What is phenotype?

Your genotype is your complete heritable genetic identity; it is your unique genome that would be revealed by personal genome sequencing. However, the word genotype can also refer just to a particular gene or set of genes carried by an individual. For example, if you carry a mutation that is linked to diabetes, you may refer to your genotype just with respect to this mutation without consideration of all the other gene variants that your may carry.

In contrast, your phenotype is a description of your actual physical characteristics. This includes straightforward visible characteristics like your height and eye color, but also your overall health, your disease history, and even your behavior and general disposition. Do you gain weight easily? Are you anxious or calm? Do you like cats? These are all ways in which you present yourself to the world, and as such are considered phenotypes. However, not all phenotypes are a direct result of your genotype; chances are that your personal disposition to cats is the result of your life’s experience with pets rather than a mutation in a hypothetical cat fancier gene.

Most phenotypes are influenced by both your genotype and by the unique circumstances in which you have lived your life, including everything that has ever happened to you. We often refer to these two inputs as “nature”, the unique genome you carry, and “nurture”, the environment in which you have lived your life.

What are the likely benefits and risks of learning about your DNA?

Personal genome sequencing is uncharted waters in our society. The benefits and risks of sequencing are likely to be connected, complex, and largely unknowable until years have passed and the consequences are examined across several generations. However, thinking through the issues surrounding personal genomics now, rather than later, may help to avoid potential pitfalls and ensure that the good outweighs the bad.

The benefits of sequencing may be mostly in the medical arena. In the long term, sequencing of many individuals could provide new information on the genetic basis of poorly understood diseases, with the potential to provide new therapies. However, there may also be immediate benefits based on our current understanding of genetics and health. Knowledge of elevated risks for known diseases could allow you to make proactive decisions about your health; visiting the doctor for more frequent check ups or screenings, choosing one type of prescription drug over another based on your metabolism, altering your diet or exercise plan, informing reproductive decisions, or making certain kinds of arrangements for your future medical care are all ways that you might use the information that you learn from your sequence. This individualized avenue of health care is often referred to as “personalized medicine”.

In addition to medical benefits, some believe that the advent of widespread sequencing could foster new connections among different people or groups. For example, people with shared genetic variants and mutations may wish to contact one another in order to discuss their common experiences, just as people living with debilitating diseases do currently (Facebook is host to many groups of people sharing information and seeking support for conditions like Huntington’s Disease, BRCA mutuations, and macular degeneration, to name just a few).

The possibility of benefits also comes with potential for harm, unintended consequences, and the altering of how we think about a number of cultural, personal, and biological issues.

Personal sequencing will likely impact our concept of personal privacy, as the technology may allow for the possible exposure our unique “code” that we leave behind on every surface we touch. In particular, even if databases storing our personal sequences are protected from the public eye, the DNA that one may discard on a used coffee cup could eventually be used to identify an individual’s physical characteristics, including race, height, facial structure, and one’s susceptibility to genetic diseases. This will likely have enormous implications for the criminal justice system, which generally seeks to increase the availability of DNA samples from the population.

In addition, there is a fear that information about your probable health care needs may affect your ability to find employment or insurance. The passage of the Genetic Information Nondiscrimination Act  (GINA) in 2008, which forbids the use of genetic information in employment and the ability to obtain and set fees for health insurance, is a major milestone.  The hope is that GINA  wil not only prevent genetic discrimination but also encourage greater participation in medical research. The Genetics and Public Policy Center has developed a comprehensive resource about GINA for multiple audiences ranging from the general public to health care professionals.

Questions abound in the areas of privacy, autonomy, and whether or not government regulation is necessary in the field of personal genetics.  Take, for example,  the procedure known as preimplantation genetic diagnosis (PGD). Embryos, created via in vitro fertilization (IVF), can now be tested for a number of genetic traits. The results can help prospective parents choose which embryo(s) to implant in a woman’s uterus. Thousands of the children in the US have already been born as a result of this process. PGD is most commonly used to to assess chromosomal characteristics or the presence of a mutation that is linked to an often fatal childhood disease.   However, in time, sequencing technology could be used on an embryo as it could be on an adult human, giving prospective parents an enormous amount of information.  This information could be a comfort and a relief in some situations but a source of worry for them and their child in other situations.

Clearly the scope of these issues is enormous, and one can argue that the potential for harm reaches beyond the ability of our societal structure to guarantee protection of individual rights. As such, it would be wise to step back and examine the big picture before we embark on our journey toward a genomic future: Who has the most to gain and the most to lose? Who bears the most risk? Where do we draw the line? And who exactly gets to draw that line, and with what authority? Genome sequencing has great potential to improve health,  create new treatments and bring about cures for disease – so how do we make sure those possibilities can be realized and minimize the risk at the same time?

Ethical Questions

If you looking to explore the many personal and social issues related to sequencing, or are considering volunteering for a genome sequencing research study or purchasing some form of genome analysis, here are a few questions you might ask yourself:

  • How much information do I want about my risks for disease? Will I learn other things I wasn’t expecting?
  • What information do I want to share, and with whom?
  • What might I learn that is both exciting and maybe surprising about my ancestry?
  • What roles do environment and lifestyle play in my personal traits?
  • How much do my genes really reveal about me?
  • How will my relatives feel about the information learned, as it could also impact them?
  • Should I share information with my health, life, and long-term disability insurers?
  • What, if any, sort of proactive decisions regarding lifestyle or medical choices should I make? Can I afford the treatments I might want or need?
  • Who owns my DNA, and the information contained within it?
  • Could this change how I think about myself, culturally, physically, emotionally?
  • What might some of the unintended consequences be for me, my family, and society?

Stakeholders and Social Implications

The stakeholders in this technology, beyond the academic and corporate researchers involved with the scientific challenges, are numerous. Doctors, lawyers, policy makers, drug companies, public health agencies, elected officials, privacy advocates, insurers of all kinds, parents, teachers, children, law enforcement and many others will face new possibilities and challenges as a result of personal genome sequencing.
But the most important stakeholder is you. Personal sequencing will provide individuals with unprecedented knowledge and access to their own genetic information. By becoming a more active and informed health care consumers, comes to the power to transform and hopefully improve medicine.