Mark S. Boguski, M.D., Ph.D. Pathology; Biomedical Informatics

Center for Biomedical Informatics, Harvard Medical School

Michele R. Berman, M.D. Editor, Celebrity Diagnosis

A number of celebrities and other public figures, such as Apple’s Steve Jobs, Google’s Sergey Brin, actress Glenn Close and rocker\reality TV personality Ozzy Osbourne, have had their genomes analyzed for clues to causes and cures of cancer, mental illness and Parkinson ’s disease. Wherever celebrities go, the public often follows and most healthcare providers are ill-prepared to educate and advise their patients about the uses and abuses, the promise and the perils of DNA analysis. Here we provide a brief introduction to medical genomics including some key definitions and resources for further reading.

(Interested in learning even more? Don’t miss the free webinar, Clinical Application of Whole Genome Sequencing, available for playback here!)

What exactly is genomics?

Genomics is a branch of biotechnology that determines the biological functions and medical significance of all of the approximately 22,000 pairs of genes that we inherited from our parents.
An entire genome of a germ cell (sperm or egg) consists of 3 billion “base pairs” of DNA distributed unequally among 23 human chromosomes (22 autosomes + 1 sex chromosome). Non-germ (somatic) cells that make up most of our bodies contain 23 pairs or 46 chromosomes and therefore contain 6 billion base pairs of DNA.
Our genes, either individually and/or collectively, influence many aspects of who we are, including our risks of developing many diseases and our ability to respond to certain therapies.
It is widely believed that genomics will revolutionize many aspects of the prevention, diagnosis and treatment of many common illnesses.

What is a genotype?

Think of a genotype like a blood type or an HLA type.
Rather than being based on antigen-antibody interactions, however, a genotype directly reflects variations in DNA.
The term genotype can apply to one variant in a single gene or all of the millions of variations in an entire genome. A particular genotype may or may not be medically significant.
There are a number of laboratory assays to determine genotypes. Two examples are DNA arrays and DNA sequencing.

Is genomics the same as genetics?

No, not really. Traditionally, medical genetics is a subspecialty focused on pediatric-onset, inherited disorders. Today, medical genomics is mostly applied to adults for one of two reasons:

Pre-symptomatic disease risk assessment
Post-diagnostic precision diagnosis for individualized therapy and/or treatment optimization

Take for example, analysis of a tumor’s DNA to identify the mutations which have caused or contributed to the cancer in order to determine if there is a targeted therapy available (such as imatinib (Gleevec®) for chronic myelogenous leukemia. Most cancers are not inherited or familial diseases. Therefore most DNA mutations in an individual patient’s tumor genome are acquired, not inherited, and only apply to that patient’s acute disease.

What do you do if a patient shows up in your clinic with their genotype already in hand and wants you to tell them what it means?

First, ask why they had their genotype done and by which company? Is the company’s laboratory accredited by the College of American Pathologists and does it adhere to CLIA (Clinical Laboratory Improvement Act) quality standards? Is the patient concerned about a medical condition that might run in their family? Are they concerned about their individual risk of contracting a particular disease? Are either of these concerns related to current medical problems? Are they concerned about the efficacy or side effects of a particular medication?

If they are concerned about a particular medication that they are already taking, check the FDA “package insert” or product label. Look for dosing recommendations and contraindications based upon genotype. Examples of two common drugs whose metabolism is affected by genotype are Coumadin® and Plavix®. You can find additional examples here (Table 1, pp. 18-19).