The two cheapest tests that query the single nucleotide polymorphism (SNP) in Complement Component 3 that we’re interested in are AncestryDNA (regularly $99, but you can find occasional sales as low as $59) and 23andMe ($199 for health & ancestry, $99 for ancestry alone, often on sale for less). As of February 2018, FamilyTreeDNA does not query this SNP, though this is also a good company, especially for mitochondrial and Y-DNA sequencing. Ancestry queries 668,942 SNPs, and 23andMe queries 638,463 SNPs (based on our test results). Both will allow you to connect with DNA relatives, but Ancestry is more sophisticated and has a broad network linked to genealogical information if this is your primary interest. Though Ancestry will provide you with more specific information on your ancestral heritage, it will not specify health or trait information like 23andMe’s health version, which is limited but updates with new information from time to time. However, there are many programs online that can extract much more health and trait information for a minor cost ($25+, to be discussed in a later post) if you prefer the cheaper price and more specific ancestral information of AncestryDNA or the ancestry only version of 23andMe. They are both good companies, so it’s up to you.
Before you order that test, you should consider the risks of obtaining your genetic information . . .
What could be the downside to knowing your genetic traits?
1. Do any laws protect my information?
Right now, there is a law in place called the Genetic Information Nondiscrimination Act of 2008 that protects against discrimination based on genetic data for obtaining health insurance or most employment (does not protect life or long-term care insurance and excludes federal employees, veterans and the military). However, laws do change, and corporations are greedy and have too much power in our government. Although people would be outraged, it’s possible the law could be repealed. Again, there is no protection for life or long-term care insurance, but I am not certain whether this has yet been an issue. In the near future, I expect that life and long-term care insurance companies will make us take a genetic test before offering coverage, not unlike the blood tests they use today to evaluate our cholesterol and blood sugar levels.
2. Could someone access your private data?
In our digital world, nothing is 100% safe since your computer or any website could be hacked at any time, but right now, 23andMe and Ancestry protect your data using standard techniques and do not provide DNA data to law enforcement without a valid court order, subpoena or search warrant. You may have heard how several cold criminal cases (Golden State Killer, etc.) have been cracked recently using an online DNA database called GEDMatch.com. This free website can provide finer breakdowns on ancestral information and certain traits and is another place to find relatives, but it is targeted at more scientific genealogical users and is less user-friendly. To use it, you can upload DNA data from almost any company (Ancestry, 23andMe, FamilyTreeDNA, Illumina, Veritas, etc.) and can even anonymize yourself as best you can, but you have to proactively upload your data. It is not done for you by either of these companies.
However, on GEDmatch you don’t have to include any personal data besides your raw data if you don’t want to, which would limit its use, and you can remove your data once you’ve found what you were looking for. More importantly, you can basically make yourself anonymous to any of these services — you don’t have to disclose your true name to any of them and can create a temporary email address or a rarely used email address to get your results if you’re truly concerned. You can also buy 23andMe kits at the drugstore so the company will never even have your true home address. You can also remove your data from any of these sites once you’ve downloaded it. I’m not encouraging you to be anonymous. That’s your decision. I just want you to know that if you are concerned about privacy, that there are workarounds so you can still obtain your genetic information, which I believe is very important.
3. Could there be results that might cause family conflict?
You may find out that you have a long-lost sibling, half-sibling or cousin or that you’re adopted, which could be joyful or could create friction in the family. We found a cousin who had been secretly adopted, and it was a joyful occasion for us. However, you may want to turn off push notifications if you have the 23andMe app on your phone. An adopted person who tested only to find out his medical risks was shocked to receive a push notification telling him he shared 58% of his genes with someone.
4. Could there be something about my family history I don’t know?
You may find out your ethnicity is not what you expected, which may change the way you think about yourself. Know though that both Ancestry and 23andMe do not have a high resolution for Native American ancestry (meaning if you have a tiny percentage, it will most likely not be detected). FamilyTreeDNA (you can upload 23andMe and Ancestry data to it) and GEDmatch are more discriminating when it comes to Native American DNA (especially GEDmatch but it may be harder to interpret).
5. Could I find out something about my health that upsets me?
You may learn that you have the C3 mutation or other bad health mutations and feel despondent. Please, don’t be!!! Knowing the genetic cards you’ve been dealt is half the battle and allows you to take action to mitigate their effects. In many cases, you can prevent these genetic mutations from manifesting as disease by your actions and lifestyle behaviors.
None of these above concerns were issues for me, but choosing to test is a personal decision, and there is no shame as to what you decide to do. I am a curious person. I want to know everything and understand my genetic heritage and which diseases correlate in our family. I believe we can take steps to work with our genetic shortcomings. To me, knowledge is power, and I want to know all that I can.
So, back to how to obtain your genetic data:*
Basically, choose the test you want (AncestryDNA or 23andMe), order it and complete the instructions to send in your sample by mail. Your data should be generated in about two to three months (though a few tests took longer for us). Log in and follow the instructions to download your raw data.
Downloading your Raw Data
Here are instructions for AncestryDNA: https://support.ancestry.com/s/article/Downloading-Raw-DNA-Data-1460089696533
Here are instructions for 23andMe: https://customercare.23andme.com/hc/en-us/articles/212196868-Accessing-and-Downloading-Your-Raw-Data
Then, open the text file that you’ve downloaded and search for rs147859257.
|
Test |
Normal will look like this |
Mutation will look like this |
|
AncestryDNA |
rs147859257 19 6718146 T T |
rs147859257 19 6718146 T G |
|
23andMe |
rs147859257 19 6718146 TT |
rs147859257 19 6718146 GT |
If you have the mutation, please don’t freak out! Importantly, when identifying a deleterious mutation, it’s a good practice to confirm it before you become too concerned. If you have the money, I’d order a test from the company that you did not originally order a test from. However, if you’ve had a few family members tested, and they also show the mutation, it is likely to be accurate.
So, if you have the mutation, I am sorry, but you may be lucky enough with your other genetics and your environmental exposures to be largely unaffected for most of your life (as several members of our family have been). As long as your inflammatory cascade is not triggered, you should be able to escape most of the bad consequences of this mutation since the inflammatory cascade has to start for C3 to become out of control. I also think there may be steps we can take to mitigate symptoms and possible long-term consequences, which I will explain in future posts. If you do have it, be cautious about head injuries, reread my first post if you get one, and read this post to see what other diseases might be linked to the mutation.
Also, if you and your spouse do not have this mutation, your children will not have it either, and so you do not need to test them unless you want to know their specific genetic makeup. I am not aware of this mutation often occurring spontaneously (de novo) so I would not worry then about your children.
If your child has this mutation and he or she plays contact sports or wants to play them, it is helpful that you’ve discovered this mutation, but there is no right or wrong answer as to what you choose to do. What is important is that you are armed with information so that if your child suffers a concussion, you can be proactive about doing whatever you can to mitigate inflammation and prevent permanent damage (see this post). We have a family member with this mutation who is continuing to play soccer, but we have a plan in place in case the worst happens. Another person with this mutation played a year of college football, and he seems to be fine so far but was lucky enough to have never experienced an overt concussion.
If you do not show either the normal or mutant results above, it’s possible that the data for that position did not meet quality control criteria (often an “X” or a “-“). Contact the company to see if they will rerun your sample and explain to them that you took this test specifically to look at this SNP (pronounced “snip”). If you have different letters instead, please let me know, especially if you have two mutations, which I am not aware of anyone ever having (at least based on what I could find in the scientific literature).
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Just a note as to how I discovered I had this mutation:
My mutation was first identified in March 2016 through whole genome sequencing by Illumina (looking at actual genome sequence, not just SNPs, and cost me $2900). I ordered both my parents’ whole genome sequences from Veritas for $1000 each (which took 8 months to receive results) to verify which side of the family carried the mutation though I was fairly certain I already knew based on family history. For Christmas in 2016, while waiting for the Veritas results, I ordered AncestryDNA for my parents and myself for fun, which was when I realized that Ancestry tested for this SNP. At that time, no other cheap service tested for it. Since then, many family members have been tested using Ancestry to determine if they carry the mutation, and we’ve also explored other sequencing services like 23andMe, which now tests for this SNP on their new chip.
*Note: Some states restrict direct-to-consumer genetic tests, like Maryland and New York, but since 23andMe is FDA-approved and AncestryDNA does not advertise diagnosing a health condition, you should be able to purchase both tests in those states without a doctor’s prescription.
Tags: C3 mutation, Genetic Tests