I’m an Addict
I admit it, I’m a genomics junkie. Ever since high school biology, when I gave a report on new DNA discoveries, I’ve been hooked. I was astounded that the instructions for creating an entire organism were contained in strands of just four chemicals. I loved how that multi-colored, twisted ladder of DNA could unzip and copy itself. And there was more. Viruses commandeer their prey by injecting their DNA into a cell. Wow! And the little bean-shaped mitochondria in cells – the powerhouse that makes our body’s energy – are really cool, and even have their own DNA.
Though I took a different path professionally, I keep up with developments in biology. I flip to the science section of my newspaper before reading the front page; I belong to Facebook groups such as I F*cking Love Science; I receive Medscape and Google Scholar updates on disease and drug discoveries.
Several years ago my friend Kate was hired by the University of Californa Santa Cruz as a programmer on the National Institute of Health’s Human Genome Project. Genome simply means the complete set of an organism’s genes, and the project itself identified the chemical sequences of human and other species’ genes. The information was put into a database, and Kate helped design and code the first genome browser, which scientists use to access this information. It is a network much like Facebook, except instead of sharing selfies it shares DNA. I got early sneak-peeks into the technology, and saw the software’s ability to analyze and present this information.
Kate showed me how to use the U.C.S.C. genome browser: you can go to any section of any chromosome of the human genome, see the genes and chemical sequences in that segment, and then compare that with a fish, or even a fruit fly. (I was stunned to see that some genes appear to be the same in all three species!)
Then I got more interested in the topic: I took an online biology class taught by Stanford University’s Dr. Robert Sapolsky, the scientist who lived in the African savannah, and studied baboons to learn how status in a primate hierarchy affects stress levels and causes hormonal changes. He later wrote the book, “Why Zebras Don’t Get Ulcers” (Answer: Because they experience only acute, short episodes of stress, like when being chased by a lion, and not chronic stress like we experience.)
Sapolsky’s course, Biology of Human Behavior, was filmed in the classroom over an entire quarter in 2011. It consists of 25 ninety-minute lectures, each one packed with the latest findings on evolution, genetics, hormones, neurotransmitters, language, brain structure, mutations, epigenetics, animal behavior, mental illness, sexuality, and more. I’d never heard anyone present so much information in one sitting, let alone in a course. Some lectures I had to watch several times in order to grasp the most basic concepts.
Does all this make me a bit of science geek? For sure, but tap into your inner nerd and join me in my genomics adventure. In Part One, we’ll learn about personal genome companies and meet some of my 951 cousins. In Part Two, we’ll examine what genes do, and don’t, predict. And in Part Three, we’ll learn more about the genomics frontier and consider the wisdom of knowing our fate.
PART ONE: OUR GENOMES, OURSELVES, OUR ANCESTORS
It’s the Real Thing
When 23andMe, the consumer gene analysis company founded by Anne Wojcicki, former wife of Google’s founder, Sergey Brin, announced a drastic price drop in 2014 (from $299 to $99), I jumped. 23andMe is one of several new PGSs, “personal genome sequencing” companies, also called DTCs, “direct-to-consumer” gene sequencing services. With 23andMe, you get a colorful kit with a plastic tube to spit into; you mail it in; and voila, three weeks later, your genetic code is available for perusal at 23andMe.com. Now, after all of this studying and reading, I could finally get the real thing. My very own genome.
What did I learn? Well, as I was to understand later, it was hardly my full genome, and not even the genes themselves, but rather something called SNPs. And the interpretation was open to debate. But we’ll get to that later.
At the start of my journey, there was a lot that was pure fun—topics suitable for cocktail party conversation or cyber posts. 23andMe tells you what physical traits you likely possess based on your genes. You get information about your ancestry and can contact people you are related to. There are videos and articles explaining the basics of inheritance, evolution, and the spread of Homo sapiens out of Africa. You can take surveys that are used to investigate correlations between genetic patterns and behaviors, conditions and diseases. You can contribute your results to the company’s scientific studies and research. But aside from all that fun, there is also some serious medical information—this test predicts your genetic susceptibility to diseases and your response to certain drugs.
Their analysis of my 23 chromosomes told me what I inherited: that I have curly hair and am of Scandinavian and Northern European ancestry. Nothing new here—I’m Swedish on my mother’s side and Bohemian/German on my Dad’s. I learned fun factoids such as my face does not flush when I drink alcohol (true), I can taste bitter flavors (true), I am lactose tolerant (true), I have brown eyes (false, they are blue-green), I am not resistant to malaria or norovirus (I have no idea), and my muscle response is that of a sprinter (maybe true when I was 20). So it’s a bit hit-or-miss.
I was interested in participating in 23andMe’s surveys for crowd-sourcing its research. Of its 800,000 customers, 640,000 have volunteered to make their data available to correlate genetic variations with characteristics. For example, the company discovered 11 genetic markers that correlate with asthma-with-hay-fever, based on analysis of 15,000 subscribers with the condition. They discovered 20 markers associated with near-sightedness, using 50,000 subscribers’ data. Most recently, they are studying their 500 subscribers with the lucky rare mutation that protects against Alzheimer’s.
Out of Africa
The ancestry analysis part of the 23andMe’s service was fascinating. I’m three percent Neanderthal! Who knew? Actually, we now know that people with European ancestors generally have between one and four percent Neanderthal genes, so I don’t feel so bad. Thankfully, I don’t have a sloping forehead or brow ridge!
I learned about my “haplogroup” – the group of people whose common ancestors migrated together tens of thousands of years ago. (Scientists have identified 153 groups.) My haplogroup on my mother’s side is “H.” I, along with everyone who is an H, descend from one group that migrated from the Near East into Europe after the Ice Age, and H is heavily represented in people of Scandinavian descent. In my group, our common ancestors existed about 40,000 years ago.
What about on my Dad’s side? Male haplogroup information is carried only in the Y chromosome, which women don’t have, so we gals can’t learn our paternal haplogroup unless we get our fathers, or sons of our uncles, to take the 23andMe test.
Even more entertaining is finding other people with whom you share genes. Here is part of my report displaying other 23andMe-ers who I share DNA with. It predicts my cousin-relationships based on how many actual sections of DNA we have in common.
So far, I share some amount of DNA with over 951 people on 23andMe, but most of them are my 3rd to 6th cousins, or even more distant than that, with whom we have less than one percent of our genetic code in common.
You can enter your ancestors’ surnames to learn more about your matches. Within a day of receiving of my results, I was contacted by Christopher, my “3rd to Distant” cousin out of Wisconsin. He saw from my profile that the Lonsdorf name runs in both of our families. It turns out, my father’s mother’s family were Lonsdorfs, from Wisconsin.
Serendipitously, both Christopher and I possessed detailed written records of the Lonsdorf genealogy in Germany back to the 1600’s. By matching the names and dates on our written charts, we determined that his father, Mark, and I are fifth cousins, sharing great-great-great-great grandparents from Nennig, Germany in the late 1700’s.
23andMe also shows you exactly what DNA you share: he and I share one section of DNA on Chromosome Six, which amounts to one-fifth of one percent of our genetic code in common. It would be cool to find out what the shared segment codes for, like height or blond wavy hair, and then see if Christopher has those traits. These would be characteristics a great-great-great-great-grandparent had as well. Unfortunately 23andMe doesn’t provide that information in any easy-to-capture fashion, although Christopher told me he would try to track this down. Perhaps we share a Lonsdorf gene for obsessive diligence and attention to detail.
There are No Lifeguards in the Gene Pool
One of the interesting things our chromosome comparison chart demonstrates is how quickly gene pools change. With each child, half of mom’s and half of dad’s genetic information disappears. Gone, forever. You can see in the table below how quickly one individual’s genetic code is eliminated through successive generations: third cousins, for example, have less than one percent of DNA in common.
Here’s another way of looking at it. I had a visit from my second cousin, Samuel Borg Olsson, from Göteborg, Sweden. He was in San Francisco for a conference on advanced fiber optics. His grandfather and mine were brothers, and his mother and my mother are cousins.
My mother’s father came to the US in 1915. He’s third from the left in the back row, with the half-smile and mischievous look. He died of TB here when my mother was three. Samuel’s grandfather, Robert Borg, is the cute kid with the bow tie in the front next to Lars, the bearded patriarch. Robert never left Sweden.
What interests me is what it means to be “related,” what “family” really means. While Christopher and I share a teeny amount of Lonsdorf genetic code from many generations back, you would think Samuel and I would share a lot more and be somewhat similar. Yet, with Samuel, the Gene Dilution table shows that he and I share only three percent of our DNA, so we aren’t likely to be too similar, which disappoints me for some reason. I wanted us to share the Swedish “Borg family” gene. But that really doesn’t exist.
True, Samuel has 25 percent of his grandfather’s DNA, and I have 25 percent of my grandfather’s, but we don’t look much alike. And Samuel does not have the height gene, which I have. I do think Samuel resembles his grandfather Robert. And while we each have 6.25 percent of our great-grandfather Lars Borg’s DNA, and 6.25 percent of Maria Borg’s DNA, these are different segments. You can see that the genetic code gets diluted and mixed pretty quickly. Bottom line – Samuel Borg Olsson and I share great-grandparents who lived in Borås, Sweden a century ago; our mothers are cousins with the same last name; but other than that, he and I really aren’t alike genetically.
So why are we fascinated with ancestry research and want to connect with distant relatives? The Chromosome Comparison and Gene Dilution tables made me think about this in a fresh way—that genealogical research doesn’t tell you as much as you would think. It mostly tells you names and locations and cultures you have in common with your ancestors, but, actually, you share very little in the way of traits or diseases, or certainly genes. Unless, of course, a group has intermarried over generations and remained in one place, then there would likely be more similarities.
Another glaring problem: most genealogical research only tells you about the male line. What about my mother’s mother, Hildur Lyseen, from Garpenberg, Sweden, and her mother? Where are the photographs of these women’s families? Where are the frayed yellowed charts in the file cabinet that show the female marriages, births and deaths back up the line? At least the gene analysis services show both sides of families. Patrimony is getting phased out there, thankfully.
Why should we care about our father’s father’s father? Why are we so thrilled that many generations back one person with our last name came to the US on the Mayflower, or further back, was a Viking? I believe this type of finding is far less relevant than in the past. For aristocratic European families centuries ago, it was a matter of economics, even life and death, to know who your ancestors were and who your offspring are. Land, titles, and fortunes passed father to son. And keeping track of the expanding list of cousins and offspring gave more power to a dynasty. Even in England today, a fifth cousin of Prince Charles would still likely be considered a “royal.” And it’s important that these cousins intermarry to preserve the dynastic name and influence.
There is another shortcoming to most genealogical research that we overlook. I have four grandparents; they have eight grandparents among them; those have 16; and those 32; and so on, doubling every generation back up the ancestral line. As we look deeper into our past, we have a lot of ancestors. In fact, it can be demonstrated that any one person alive today is related to everyone who ever lived at one time—and only about 1,000 years ago in Europe. That’s 40 to 50 generations. This notion should diminish the glory of having your ancestor be Louis XVI, Leif Ericsson, Genghis Khan or Muhammad – since the remaining millions of your other ancestors in that generation a millennia ago were probably serfs, scoundrels and scullery maids
We are Family, Get up Everybody and Sing
But still, Samuel is family And since my grandfather died young, I am curious about that side of my family. And Christopher is family, too. What’s more, on 23andMe I can see 951 people around the world with whom I share at least one decent segment of DNA, with whom I have about 1/10th of one percent of my DNA in common.
Just as I am related to everyone who was alive 1,000 years ago in Europe, the converse is true. Everyone of European descent alive today shares one common ancestor who lived just 1,000 years ago. If we narrow the group to a regional population, say, Swedes, we all could have a common ancestor from 500 years ago. So in the broadest sense, we are all related.
And sometimes gene sharing is a good thing. Sapolsky explained that reproducing with one’s third or fourth cousin actually gives the best results for the survival of a species. A study in Iceland demonstrated that marriages with those levels of relatedness produced more children and grandchildren than all other relations. This is due in part because mother and offspring are likely to have blood type compatibility, which reduces the chance of miscarriage.
But we also know that offspring of close cousins are likely to end up with detrimental recessive genes from both parents. The most famous example is the Spanish Hapsburg dynasty, where cousins, uncles and nieces frequently married over the family's 200 year reign. In this case, disfigurement—the jutting Hapsburg jaw—illness and infertility were common.
Why else do we care about our extended genetic family? It has something to do with “kinship” and “tribe.” We are hard-wired genetically to recognize and stick with our own kind. All animals have a similar molecular signature in their pheromones that allows them to recognize relations through the sense of smell. This signature is in the genes. For humans, recognizing pheromones is generally unconscious. And why do we need to know who is family? It turns out cooperative behavior among relatives helps ensure that individuals and their species survive. And we compete with non-relatives to attain sufficient resources for our tribe. This is called “kinship selection” in genetics parlance, and means that not only are the fittest individuals likely to survive, but the fittest kinship groups are likely to survive and pass on their genes.
This is why we identify with our ethnic, familial, and cultural backgrounds. In the 23andMe Community posts about half the comments were from people almost wistfully seeking others in their haplogroup – their original millenniums-old tribe. And genetic tribal behavior explains a lot about war – why the Serbs, Croats and Bosnians were at each other’s throats for so many years, or why the Ukrainians of Russian descent identify with Russia (their pheromones and genes) rather than with Ukraine (their country with its politically-generated borders).
So what about my nearly 1,000 cousins, aunts and uncles on 23andMe? Should I throw a huge family reunion party for my extended family in Stockholm or Prague or Nennig, Germany? I just hope no one gets drunk and spills family secrets (or wait, maybe I do!)
Coming Up Next
There used to be so much more than ancestry, cousins and haplogroups to dig into on 23andMe. In Part Two, we look at the hard science behind 23andMe, and why the FDA tried to put a stop to it. (Spoiler: They only partially succeeded)