My Beautiful Genome

by Lone Frank

  I’m not sure what group I belong to, but I would like to take up the hunt.

  “Your 16.193T mutation is rare and is not found in everyone in haplogroup H2a1, so that’s good to search,” he offers as a tip. “And remember – the databases are growing all the time, so if you don’t find anything today, it may be you will be lucky in six months or a year. Keep on trying. Good luck.”

  I’ll need it. When I go to Sorenson’s own database and search among Y chromosomes, I find no complete match, and there is no hit until I lower my requirements a tad. I ask the database for people who share eight out of ten genetic markers; it serves up a handful. But when I go in and look more closely at these examples, all of which have surnames that are anything but Pedersen, the statistical programs estimate that there are between nineteen and thirty-two generations to our most recent common ancestor. That doesn’t help. I keep working but there is nothing in either the Y-search or the Y-base databases, so I quickly abandon the male line and shift over to search mitochondrial DNA.

  This is not without hope. I know that one of the daughters of my great-grandmother Gjertrud Rosenlund emigrated to America in the previous century, and it is not entirely improbable that some of her descendants may have been gene-tested. Why not? Genealogy, after all, is the most popular hobby in the United States.

  So I feel a little tingly when I start up the Sorenson search machine, but the result comes up lightning-quick – and empty. No one provides a complete match. I try again, searching by haplogroup, and it appears that, out of eighty thousand in the database, of which by far the most are of European extraction like me, only 385 belong to H2a1. Of them, a paltry seventeen have both of the important mutations, 16.354T and 16.193T.

  For all intents and purposes, that’s practically no one. And not a single one of them shares my other mutations.

  I feel at once pleasantly rare but also unsatisfied, and I have a strong urge to keep hunting. The next possibility is Mitosearch, a database available to the public, from which you can gain access to individuals whose mitochondrial DNA has been tested by Bennett Greenspan and the Genographic Project. I follow Ugo Perego’s recommendation and search my mutations. In fact, I find two that match. Both are men – one from the Ukraine and the other from Finland. Unfortunately, I can see that they have been tested for fewer markers than me, so it is impossible to know whether they also fit with my other mutations. It looks like the trail has petered out, but not quite.

  By chance, I run into a volunteer DNA project, Danish Demes. It is one of the many examples of amateur genealogists who throw themselves into doing something that approaches research or, at least, lends itself to research: a group that tries to map the network of kinships that exists for Danes both in Denmark and around the world. At the moment, they have fewer than a hundred participants, but I spot at once that two belong to haplogroup H2a1. I check their mutations. They are not exactly like mine but not far off, and I feel so encouraged that I write to the project’s anonymous administrator and ask to be let in from the cold.

  “You would be very welcome,” writes the organizer, who turns out to be an elderly, hard-of-hearing lady from Florida. A retired zoologist, Diana Gale Matthiesen is a genealogical veteran, with decades of experience and a clear veneration for DNA tests, which she calls “the best thing that’s happened since the Internet.” Her dear, departed father was Danish and, after researching her mother’s family to the bottom and identifying many distant and unknown relatives, she wanted to get “closer to her Danish roots.”

  But Diana’s ambition goes much further. She wants to construct a specialized database of Danish haplogroups and a catalog of the specific mutations found in individuals in each group. She envisions a project that will become a gold standard for people who believe they have Danish roots but are not sure where to go or with whom to compare themselves. At the same time, it will be a resource that true professional geneticists, anthropologists, and historians can use freely in their research.

  From the outside, it seems bizarre. I’ve never given a thought to the distant past or unknown ancestors, and now I volunteer to provide a set of mutations to cyberspace. Propped by coffee and candy, I sit up into the wee hours of the morning, searching for strange people who share something as abstract as the chemical building block thymine in a particular position in the circular chromosome of their mitochondria. I’m searching for a trace of a small and, presumably, completely meaningless change that arose some thousands of years ago in a single woman. A nameless ür-mother who cannot be traced but has passed on a hidden sign to an unknown number of descendants. I wonder whether I will feel any kind of kinship if I found others out there in her multibranched family tree.

  At any rate, the fascination has worked its way into me, and it is beginning to resemble a form of identification. Sometimes, I think of myself as belonging to a special haplogroup and the carrier of a special mutation and, in a way, these thoughts give me a strong experience of the very meaning of genetics. I can sit quietly with a powerful feeling that we are each of us temporary depositories of information that has an almost eternal life, and which is passed on and on and on. At the same time, the idea is a gateway to a genuine sense of broader kinship. A kinship that we, of course, know exists between us and the rest of humanity and the living organisms of the world, but which otherwise seems so abstract.

  The whole experience is also a gateway to a fascination with the information itself. I want to get closer to my genome – my digital me – and decide to take the next logical step. I will put mitochondria and Y chromosomes behind me and take a completely different type of test, one that involves my entire genome. A test that casts a net over the six billion base pairs and captures some of the countless tiny variations it contains. Variations that, according to researchers, will provide a picture of my prospects for health and for disease – a picture not of my past, but of my future.

  3

  Honoring my snips, in sickness and in health

  DEAR LONE FRANK:

  We are pleased to inform you that the results of your deCODEme gene scan are now available. Please click here.

  IT’S ALWAYS NICE to get a message that is straightforward, and I do as I’m told. A little tap on the mouse, and I gain access to my personal deCODEme page, which assures me that the company has tested my genome for more than a million genetic markers. Excellent. Some of the research has already found a risk of disease, and, as it says on the screen:

  Your results include forty-six medical conditions. Find your risk and read about prevention.

  The message seems friendly enough, but my mouth still goes a little dry. Three weeks ago, at home on the sofa, it was pure fun and high jinks to rip open the envelope of instructions I had received through the post; nor was it any big deal to swab the inside of my cheek with the stick supplied by the kit and send my little scraping of mucous membrane back to Reykjavik for analysis. But right now, here in front of the computer, my desire to see into the future has abated. Somewhat.

  The thing is that there is no such thing as a flawless genome. We are all mutants with ticking time bombs hidden inside. I know that theoretically, but as long as I don’t have a precise picture of where those mutations exactly are, it all seems safely hypothetical, unreal.

  To top it off, I’m alone and far from home. I’ve gone to Reykjavik to talk to the people at deCODE Genetics and have installed myself at a hotel on the city’s main street. Although it’s the start of spring and the sun is out, there is a thin but pleasingly decorative sheet of snow over everything, and the temperature has stayed stubbornly below freezing point. Iceland’s capital is bleak and windy and, even in the hotel room, I’m constantly cold.

  It’s late in the afternoon and dark outside, and I have opened a large can of beer for a little company. I glance down at the “medical conditions,” which are broken down into categories according to which organ they affect. Blood diseases, joint and muscle disorders, digestive problems, eyes, lungs, and throat.
Cancer, brain, nerves. Hair, skin, and nails are there, too.

  It’s an indiscriminate mixture, as the eye wanders down the list: glaucoma, sclerosis, kidney cancer, asthma, gallstones, baldness (for men only), type 1 diabetes and type 2, restless leg syndrome, gout.

  I pause. Gout? Is that even genetic? I thought that was something crusty men got after a lifetime of overindulgence. Too much foie gras and port, deposited as uric acid in the joints of the big toe.

  IT IS SURPRISINGLY simple to put together a gene profile. Most of the work is automated and takes place inside machines and computers, almost untouched by human hands. The tiny amount of DNA in my mouth swab is cultured in a copy machine designed for that purpose – an apparatus that starts a polymerase chain reaction, in which specialized enzymes meticulously pull apart and multiply the DNA molecules, hundreds of times over. After this step, the whole thing is poured into a gene chip that measures a million tiny SNPs distributed throughout my chromosomes.

  A very few of these SNPs are known to be connected to certain diseases, in that they increase or decrease the risk of getting them. Take, for example, someone who has acquired the unromantically named rs9642880, which is found on chromosome 8. By comparing SNPs in almost two thousand Icelandic and Dutch patients with bladder cancer with those in thirty-four thousand healthy “control” people, the researchers at deCODEme and a number of European universities discovered that rs9642880 apparently increases the risk of that cancer. One in five people of European descent has base T at this position, and it gives them a 0.5 times greater chance of developing bladder cancer at some point in their life than a person with base A, G, or C.

  If you want, you can read through corresponding studies for other diseases and their markers. Likewise, you can inform yourself about the technical details that form the basis for the risk calculations. I go to the page with these long equations and have to admit that I don’t much feel like dealing with them right now – I want to look more closely at my genetic horoscope, my digital self.

  Where do you begin? I decide to start offensively, draw the mouse a little uncertainly over a number of cancers, and finally click on chronic lymphatic leukemia. The text presents the symptoms of the disease dispassionately: extreme exhaustion, headaches, bleeding, and depressed immune reactions. Finally, it explains that it only strikes half a percent of the population and, typically, after they reach seventy. Before I can get my personal odds, I have to click that I understand and accept: Do I really want to see the results and do I understand what they represent?

  This is what the modern version of informed consent looks like. Some brief sentences on a screen and two clicks of a mouse. Of course, there is no doctor or researcher present who could explain to me what I might not understand, so what can I do? How can I stop myself from clicking the buttons, one after the other, without a second thought? It’s a little like the fine print in contracts and insurance agreements – you just don’t feel like reading it. But I know I’m capable of understanding a risk presented as a percentage, so I quickly click “Accept.”

  Ha! It begins well. My lifetime risk for chronic lymphocytic leukemia is only 0.2 per cent, two out of a thousand. That is almost forty percent less than the average for white European women. I feel as though I’ve just won on a lotto scratchcard.

  I look down at the other choices and happen on intracranial aneurysm – a scary out-pouching of a major blood vessel in the brain that, without warning, can burst and leave you a vegetable.

  Another winner! Only a three percent lifetime risk, which again, is half the normal rate. Now I’ve tasted blood, so I check age-related macular degeneration, or AMD, the progressive breakdown of the retina that was the subject of one of the first association studies and is the most frequent cause of diminished vision and blindness among older adults. Researchers have found gene variants in five regions of chromosomes 1, 6, 10, and 19 that come into play and affect the risk. I think of an acquaintance back home in Copenhagen, a woman who has been an avid reader and a professional translator of literature all her life but is now pretty much blind, relegated to audiobooks and dependent on the help of other people to get around. I hesitate for a moment. My fingers hover over the mouse. Yet once again I click, and find myself far below the average population risk. A paltry two percent, versus the normal eight. I toast myself in the mirror, which happens to be hanging over the desk, and decide to take on one of the heavies, while my mood is buoyant.

  Alzheimer’s. The most frequent cause of dementia, it says. Here, I can’t help but think of old James Watson and his fear of carrying the ApoE4 gene variant, with its significantly increased risk. But when I read my results, they are outright fantastic – not a single ApoE4 variant in sight. Instead, I have two copies of ApoE3, which is connected with a low risk of Alzheimer’s disease and gives me just a seven percent chance of developing the devastating disease, whereas the population average is twelve percent.

  My dad was right, I do have good genes! And spontaneously, I think of a friend at home and how she keeps urging me to get down to business and propagate before it’s too late. “When you’re hale and hearty, highly educated, and fairly bright, it is a duty to society to have children who can raise the standard,” she lectures. My friend is herself highly educated, extremely bright, and has so far done her duty to society three times.

  But it’s time to stop stalling. I know where my problems are likely to hide – we all do. I have a family history of diseases running through generations. On my father’s side, it is cardiovascular problems. My paternal grandmother, my grandfather, and my father – all weak hearts and lousy blood vessels. My grandmother suffered from an indeterminate “bad heart,” as it was called then. My grandfather had poor circulation and sores on his shin that wouldn’t heal and, even though he worked like a horse all his life and was apparently in fine form even at a high age, he was struck by a debilitating cerebral hemorrhage right after hitting seventy. And my father. In his forties, he was diagnosed with seriously high blood pressure – so high that the family doctor called for an ambulance to freight him directly to the nearest hospital. Somewhat later came the trouble with his heart, which fluttered and would not beat regularly. Pills and medication piled up and were changed endlessly, but they could not prevent him from developing arteriosclerosis in both legs. In the end, there was no pulse left. My father, who had built his own house and did handsprings in the back yard, could barely walk and silently fumed about his physical decline.

  “I’ll do fine as long as I’ve got the radio and a library full of books,” he said, but, after a while even sitting in a chair began to hurt so much that he just wanted to get away. It was peripheral arterial disease, or PAD as it is now popularly called. And sure enough, deCODEme had PAD listed, right under the category of heart and circulation. They can inform me that the condition strikes more than one in ten people in the industrialized world and that smoking is the grand villain behind it. But genetic factors have also turned up; Icelandic researchers have discovered a single meaningful variant on chromosome 15.I take a deep breath and click.

  I knew it – it doesn’t look good. Now, my personal risk is suddenly increased in relation to the norm, to around eighteen percent as opposed to fourteen. It may not be a colossal difference but, in absolute terms, almost one in five. As if that weren’t enough, deCODEme even stresses that their test “may not include all risk factors.”

  I no longer smoke but get clammy palms thinking about my younger years, when I was a party smoker. Weren’t there an awful lot of parties back then? I check for what they have to say under prevention and treatment, and it shows that you can take blood-thinning aspirin to reduce the risk of PAD. Maybe I should take it up with my doctor, when I get home.

  It has made me tense and, since the can of beer is long gone, the only way to curb the feeling is by attacking the minibar’s store of chips and chocolate. In the mirror, I catch a glimpse of myself flaying the wrapper off a Snickers bar and think: “Come on. Get it o
ver with.”

  Heart disease and hardening of the arteries are not nice options, but my greatest anxiety is reserved for something else. What I’m really afraid of is breast cancer. A horrific disease that, somewhere in the back of my mind, I’m certain I’m going to die of, just like my mother and my maternal grandmother.

  Some of my earliest memories are of visits to my grandmother at the radiation ward of Århus Hospital. Grey linoleum floor, high glass doors, and weak Kool-aid. When it got to be too much with the adults, who were all sitting very still, I could play with the little boy with a large brain tumor. They had shaved off all his hair and indicated with a purple marker the areas of his head that were to receive radiation treatment. It looked like some exotic map, and I remember those purple lines almost better than my grandmother’s illness – but then, I was only four years old and did not understand the gravity of the situation.

  It was infinitely worse when I started secondary school, and it was my mother’s turn. One day, she came home from work and told me and my little brother, with whom she lived alone, that she had cancer and was having her left breast removed the next week and that the doctors didn’t know how bad it was.

  There were tears, angst, and hope that it had not spread, but it had – possibly not very much, so there was hope that radiation and chemotherapy would work. They did, and my mother was free of disease. But only for six months. Then, there were spots on the scans. Small spots but still … It turned into more than three years of hope, examinations, disappointments, new treatments, agony, depression and, eventually, pain. Nights when she screamed and whimpered because the pain from the bone metastases was difficult to curb even with morphine.