I recently bought 23andme, a service which requires you to send off a DNA sample, and in return performs a series of interesting tests concerning your health and ancestry. I bought the test as a birthday present to myself, somewhat because I was interested in the results, but also because I wanted to treat it as a catalyst for learning more about the subject.
The first step in the process of getting your DNA analyzed by 23andme, is to put a substantial amount of saliva into to a specialized container they mail you. This saliva contains cheek cells, which is what 23andme use for genotyping. They don't need many cells, but the reason why they ask for so much saliva is so that it's harder to take someone else's DNA without their permission!
Then the DNA sample is mailed off to 23andme's laboratory where it's amplified through PCR, a process where the DNA is separated from the nucleus and replicated. Lastly it's put through a machine which, rather than sequence the whole genome, looking for specific SNPs. These SNPs are responsible for a lot of the biological differences between people, and variations influence a variety of traits such as height, eye color and disease susceptibility.
So now 23andme have analyzed about a million of your SNPs, it's time to draw some conclusions from the genotyping. Most of the health and trait reports are based on genetic association studies, taking a specific SNP and testing for associations with factors like eye color and diseases like Parkinson's. Furthermore, 23andme can correlate diseases and symptoms from all their users to specific SNPs, furthering research and understanding of how they affect our bodies.
Genetic associations are not a certainty that a specific SNP will have a specific outcome, but rather a probability. Correlations doesn't mean causation either, and while there may be an association, additional research is needed to show whether the factor has a causal effect.
There are a bunch of heritable genetic disorders that 23andme tests carrier status for, such as Cystic Fibrosis. While the gene for Cystic Fibrosis is recessive, if you mate with someone who also has the same recessive gene, then the likelihood is that your child will develop the disease is one quater. Other disorders like Huntington's are dominant, and only requires one parent to be a carrier. 23andme doesn't seem to do much testing of dominant genetic disorders, as it's likely that the parents are already aware of the issue.
Working out how SNP affects a phenotype trait is tricky. Most SNP changes have no effect, while other characteristics are due to environmental factors. One way of investigating this, is by studying identical twins. Since they have the exact same DNA, any differences between the two can be attributed to environmental factors. Some phenotypes like height are mostly influenced by your genetics (assuming you have a good nutrition), while others like freckles are more affected by the environment.
This difference between environmental and heritable traits is often called nature vs nuture, and can be fairly controversial at times. Take, for example, IQ. The effect that parents have upon their children's intelligence is in serious dispute and, while a neglectful and abusive upbringing can have an adverse effect, given a base minimum supportive parenting doesn't have have much of an influence on IQ. Studies have shown that identical twins who grow up in separate families have an IQ correlation of 0.74, while adoptive siblings have no more similar IQ than strangers.
I'm not going to talk about the more sensitive health information I gleaned from the report, as while President Bush signed the Genetic Information Nondiscrimination Act I'm still wary of how it could affect my insurance in the future. However, let's talk about a non sensitive trait, lactose intolerance. Lactose intolerance is fairly heritable and is influenced by an SNP near the LCT gene which encodes lactase, an enzyme required for digestion of milk.
Normally, the lactase enzyme is only produced in the first few years of a mammals life. However, certain European populations have a mutation that causes lactase to be produced throughout their lives. Dairy farming, which is widespread primarily in Europe, provided additional sources of nutrition to early inhabitants of Europe. Thus, it is thought, being able to drink milk throughout adulthood would have provided them with an evolutionary advantage.
My genotype for this SNP is AG, or adenine and guanine. This has been correlated with higher adult lactase levels. This allele is rarer in Africa and Asia, hence the high cases of lactose intolerance in those regions.
SNP: rs4988235 (A or G)
Alex's Genotype: AG
As I say, while this trait is heritable, it is also influenced by environmental characteristics such as the bacteria in your gut. In other words, having a AG genotype doesn't always mean you'll be lactose tolerant, and vice versa. It's all about probability, and in this case 23andme were correct - I am lactose tolerant, which is useful as I enjoy milk!
Calculating ancestry through DNA is an interesting process, because it turns out that the variations between you and your ancestor's DNA make it impossible to detect relations after a few generations or so. However the Y chromosome is passed down from father to son without much alteration, which means it makes a perfect candidate for looking into your past. Maternal descent is calculated from DNA found in the mitochondria, as this too is passed down unaltered from mother to child. Using these two pieces of information we can look hundreds of thousands of years into our past, as well as at our more recent history.
My ancestors, on both my mother's and father's side, are from Europe - mostly from the UK, Ireland and Scotland, with a little Spanish and German mix. My DNA is 2.9% neanderthal, which puts me in the top 91% of 23andme's members (not sure what conclusions to draw from that!). I'm also distantly related to Jesse James on my mother's side, and have found a previously unknown second cousin in Scotland.
Genetic family trees can be identified by looking at haplogroups, a set of genetic mutations that are shared by everyone in the group. The likelihood is that if you share a lot of specific genetic mutations with someone, than you're related. All haplogroups can be traced back to a mutation in a single individual.
For example, 8 percent of asian males are in the same haplogroup as Genghis Khan, and carry Y chromosomes that share many of the same SNPs. Y chromosomes aren't recombined when they're inherited, so genetic mutations in them act as markers, allowing geneticists to trace them back and predict in time the moment they occurred. Such a rapid spread of this particular mutation is unlikely to have happened by chance, and suggests that 0.5% of the world's population are descendants of Genghis Khan and his male relatives - quite a staggering amount.
Geneticists can trace back humans to a single male and female, a genetic "Adam and Eve". What's fascinating is that while Adam lived about 142,000 years ago, Eve lived much earlier, about 200,000 years ago - they never met each other. Y-chromosomal Adam lived at a time close to the migration from Africa, and this turmoil could suggest a reason why so few males lineages survived.
Analyzing my DNA has given me a fascinating insight into my health and ancestry, and something I'd recommend to everyone. However, personally the best part of the whole process was learning more about DNA and how it effects us. It's a fascinating subject which is undergoing a lot of research.
On a separate note, 23andme's service is really commendable. Businesses that combine commercial products with scientific research and advances are close to my heart. Other examples of this kind of approach are SpaceX and Tesla.