Editor ’ s Corner
Learning to Love Your Genome
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The content of the Editor ’ s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated .
HE DAILY CIRCUS of recent world events has left me wondering whether it is truly plausible that I share a genome with the other half of the population , or whether my alienation could be explained by a heavy burden of Neanderthal DNA or excessive cilantro hypersensitivity ( it ’ s a thing – look it up ). To explore this hypothesis , I had my genome sequenced .
Proving that this is an emerging obsession , I did it serially , in various formats , hidden like a secret bottle of gin from an unsuspecting family . Truthfully , only a small part of the Stewart blueprint was analyzed and reported at any one time , perhaps feeding my craven need to indulge more .
The first foray involved a $ 2,900 whole-exome sequencing from which I learned I am a carrier of four heritable diseases ( for anyone who cares or is brave enough to marry my children ): Niemann-Pick disease type C , galactosemia , hemochromatosis , and spinal muscular atrophy . I was reassured that I did not carry a particularly noxious mutation that has plagued a branch of my immediate family for the past 50 years . I also learned that , if my pharmacogenome is to be believed , I should take higher doses of warfarin , lower my doses of statins , and pretty much forget about using antidepressants .
Admittedly , like a CIA operative , I was initially underwhelmed by the paucity of data . But on reflection , what the genome did not reveal proved to be more interesting . I tested negative for 1,596 other known conditions , including genetically based cancer and neurodegenerative predispositions . My relief is tempered , though , by the hard-to-ignore clinical zinger that , in the past few years , I have become utterly unable to recall anyone ’ s name three minutes after being introduced .
Still , I felt perky about my “ negative ” result and settled on the possibility – or perhaps the alternative fact – that I had reduced the cost of my future health care by avoiding the need for repeat genetic testing , making drug adverse events less likely , and allowing more informed future family planning ( probably best if no one forwards this latter conclusion to my wife ).
So , what if such testing were routine and we all participated ? Would these conclusions be generalizable ? Even in my own iron-overloaded , lipid-accumulating , metabolic minefield of a genome , the logic for hematologists to embrace such a path reveals itself when we consider the possibilities of identifying and reducing the disease burden of global plagues such as sickle cell anemia , thalassemia , hemophilia , and cancer .
Inspired to learn more , I have mainlined genomic testing for the past three months . A venture into ancestry confirmed I am resolutely Scottish ( go figure ) and , thus , can blame a lack of more “ exotic ” DNA for my refusal to dance at weddings . I hold out hope that the pending results from my $ 149 National Geographic Genographic DNA Ancestry Kit will reveal some Genghis Khan or caveman lineage – explaining my misanthropy .
Next came whole-genome sequencing – this time for $ 999 . I should have quit while I was ahead . I opened the latest electronic report on a grey day in January , in an airport hotel in
Brussels ( think “ Manchester by the Sea ” dubbed in Flemish ). Failing to read the small print , I slowly focused on the word “ Alzheimer .” This resulted in a really awful , most unpleasant , distinctly uncomfortable 15 minutes , until I realized that the words “ typical risk ” were on the right side of the screen , just out of sight on the mobile app .
Recent data show that around 3 percent of the average adult population have an unsuspected inherited and medically actionable genetic finding , while 80 to 90 percent are carriers of inherited disease , and pretty
Keith Stewart , MBChB , MBA , is Carlson and Nelson Endowed Director of the Center for Individualized Medicine and Vasek and Anna Maria Polak Professor of Cancer Research at Mayo Clinic in Scottsdale , Arizona .
much everyone has clinically relevant information in their pharmacogenome .
My own experiences aside , the rapidity of progress in genome sequencing is astonishing . It is easy to forget that only 15 years ago , no human genomes were yet sequenced . Now , genetic prognostication and targetable mutations are routinely used in treating blood cancers .
At our own clinic , families with rare diseases have whole exomes sequenced each week with clinical diagnostic intent , healthy individuals are counseled on the role of predictive genomics , and pharmacogenomic alerts fire in the electronic health record on a daily basis . A rapid genome-sequencing program in the neonatal unit is active , and individualized medicine clinics for bone marrow failure syndromes , inherited cancer , hyperlipidemia , arrhythmia , peripheral neuropathy , inflammatory bowel disease , and pediatric liver disease are up and running . Genomics-based diagnostics are being built for inherited bleeding , myeloma drug resistance , and leukemia gene fusions . Plans are afoot to offer a low-cost , medically relevant genomic screen to any interested patient , and a deep dive into the uncharted territory of the circulating tumor DNA atlas is under way .
All of which suggests that you may soon need a crash course on the molecular basis of asparagus odor detection , wet ear wax , and photic sneeze reflex – all of which were reported to me in my genome journey . In case you are still dying of curiosity , I am indeed genetically overly sensitized to the bitter taste of cilantro , I have a trait associated with a longer index finger ( but surprisingly not middle ), and I can now understand why I hate the sound of people chewing : It ’ s called “ misophonia ,” for the poorly informed . The wonders of the genome indeed .
Keith Stewart , MBChB , MBA
Have a comment about this editorial ? Let us know what you think ; we welcome your feedback . Email the editor at ACNEditor @ hematology . org .
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