All I Want for Christmas Is My Genome Sequenced

Written by: Kiri Sunde, an undergraduate Carolina Scholar at UNC-Chapel Hill, majoring in Quantitative Biology and Mathematics:

Nineteen ninety was a big year for me; I was born.  It was also a big year for the world of human genetics – the year the Human Genome Project was initiated.  Completed in 2001, the publically funded project cashed in at $3 billion.  Now, just a decade later, I have had one million SNPs across my genome sequenced for under $100.

As a biology major with a strong interest in medical genetics, I had been following the personalized genetic medicine movement from a safe distance for several years.  When I took Dr. Hogan’s introductory genetics class in 2009, I learned that it would not be long before individuals could have their entire genome sequenced for under $1000.  At the time, the idea seemed entirely abstract.  It did not really occur to me that, before I graduated from college, I could have my own genome sequenced, at least not until one of my professors mentioned a few months ago that he sent his DNA sample to the “boutique” genotyping company 23andMe and reported a positive experience.  This idea was no longer purely theoretical, and the prospect of decoding my own DNA was too enticing to resist.

That evening I called my parents and asked if I could have my genome sequenced as my Christmas present this year.  They gave an unhesitant “yes,” hopeful that the test might unearth information about my dad’s heart disease, late-onset type 1 diabetes, and mitochondrial myopathy, and my mom’s family history of breast cancer.  Opinions from my friends pretty much fell along party lines: science majors in approval and humanities majors mortified that this, of all things, is what I wanted from Santa.

Within days a sleek package bearing the company’s slogan, “Welcome to you,” arrived in my mailbox.  As instructed, I spat unceremoniously into a tube, packaged it up, sent it off to California, and began my six-to-eight-week wait with patient anticipation.

After just three weeks, the “new mail” chime of my inbox announced that my results were ready to be viewed.  Lying in bed in my pajamas at 7 PM and watching TV alone, I was caught off guard.  Was now really the time to reveal the secrets that my genes had been keeping for 21 years?  And was it really just a click away?  I was the kid who refused to check my inbox for weeks at a time during the college admission season because opening an email just didn’t compare to the excitement of coming home to check for the big envelope in the mailbox.  This, on the other hand, seemed so anticlimactic – no buildup, no doctor’s office, no family or friends by my side.

I took a deep breath and dove in.  The website was easy to navigate, with tabs organizing my genomic query into the categories of disease risk, carrier status, drug response, traits, ancestry painting, and relative finder.  The disease risk results were sorted into three categories – disease for which I am at, above, or below average risk.  I was pleased to see that the “increased risk” list dwarfed in comparison to the other two.  My only truly elevated risk was that for melanoma, but such a finding was based on a single SNP for pale skin tone.  Fortunately, from my youth, my mom was smart enough to put the two together without such sophisticated technology; she had always slathered SPF 50 on my ghostly white skin and restricted my outdoor play to the morning and evening when the scorching Georgia sun was at bay.

The test revealed that I was, thankfully, at significantly reduced risk for several devastating conditions including multiple sclerosis, macular degeneration, and type 1 diabetes.  Still, for some of the most common causes of illness and death in America – coronary heart disease, type 2 diabetes, and several cancers – I am at average risk.

There were three diseases for which I had to make a deliberate decision to view the results.  The decision to unlock my BRCA results was an easy one.  A cancer-causing BRCA mutation, though devastating and not unlikely given my family history, would be actionable.  I did not hesitate and was pleased to learn I did not carry any of the most common BRCA alleles associated with breast cancer.  The other two locked results – for Parkinson’s and Alzheimer’s – were somewhat more daunting.  In anticipation of receiving my 23andMe results, I did not expect to be timid about accessing any of my genetic information.  At least in theory, I would rather know if I have the ApoE4 allele, plan my life accordingly, and hope for progress to be made in the treatment of Alzheimer’s over the next several decades.  I hate uncertainty, but when the results were there in front of me, I realized I may have underestimated the gravity which reading these two pairs of As, Cs, Gs, or Ts could hold.  I wasn’t so sure I wanted to know if I would succumb to such a grim fate, at least not while I was lounging in my PJs.  I sat on it for a few days before my curiosity and rationality won out.  I do not have ApoE4, giving me below-average risk for Alzheimer’s, and my risk for Parkinson’s is just about average.  Relief.

After the weightiness of exploring my disease risks, I was pleased to move on to the lighter “traits” category, where I learned that, big surprise, I probably have curly hair, blue eyes, and wet ear wax.  Somewhat more revealing, I discovered that I am a slow metabolizer of caffeine.  I often wondered why I did not seem to tolerate the coffee load on which my collegiate peers thrived – no, subsisted.  This is likely the reason.

As amazed as I was with the accuracy of a few of their assessments, I was equally struck by how primitive our knowledge of much of the genome remains.  At six feet tall, I fall in the eightieth percentile for height… of men.  But the best 23andMe could do was guess that I might be 0.3-0.7 cm taller than average.  Accordingly, I know to take many of the other results, including the disease risk calculations, with a grain, or even a spoonful of salt.  Studies have that shown different genotyping companies give vastly different results for the same DNA sample.  Even when they agree on a certain risk, it’s still no more than a statement of probability.  We’re still just rolling the dice.

Has the test changed my lifestyle?  No.  I already exercise regularly, abstain from drugs and smoking, and eat a balanced diet (aside from my sugar addiction, for which there appears to be a SNP I can blame.)  Everyone should.  Has it given me any clinically actionable results?  Not particularly.  If I decide to have children of my own, I’ll make sure my spouse gets tested to confirm he is not also a carrier for hemachromatosis.  That’s about the extent to which the test has actually changed my life.

Even so, getting genotyped has brought me peace of mind, on some level, to know that standard doses of Plavix and Warfarin won’t kill me and that my children won’t have cystic fibrosis or PKU.  The release of these psychological burdens is, in my opinion, worth something.  The test has also brought me to think about genetics on a deeper and more intimate level.  In Biology of Blood Diseases, my professor lectured on the Factor V Leiden trait as a risk factor for deep vein thrombosis.  Before he could finish the PowerPoint slide, I had logged in on 23andMe, accessed my genotype at that exact locus, and was confirmed that I did not have this trait.  When test time came around, I had an actual context in which to answer his questions about Factor V Leiden, more than mere textbook knowledge.  The information stuck because it was personally relevant.

Humans are inherently driven to care about what’s personal.  This technology may not live up to claims that it represents the next era of medicine – the so-called personalized medicine revolution.  Regardless of its impact (or lack thereof) on my daily life, I think the fact that I can spit in a tube to read my personal genetic code is plain awesome.