What’s Your Type?

We are all unique, and knowing our genotypes at specific places in our genomes may give each of us a better understanding as to why.Helix with an alphabet made up of just four letters –  A, T, C and G.

Those four letters represent the nucleotide bases – adenine, thymine, cytosine and guanine – that are the building blocks of life. The sequence of A’s, T’s, C’s and G’s run in long stretches of code that instruct the way the human body is built and functions.

In 2003 after ten years and $3 billion, scientists decoded the first sequence of a human genome. Since then costs have dropped for sequencing a genome to as low as $1,000. While very inexpensive in comparison, it would still be prohibitive for most consumers to have their full genome sequenced.

So how is 23andMe able to provide genetic data to so many people at an affordable price in just a matter of weeks?

The secret lies in a process called “SNP genotyping.”

If you compared two unrelated individuals, you would find that their genetic sequences are about  99.9 percent the same. It is that miniscule variation in their genome that makes all the difference. It’s what makes us each unique.That small variation is also the key to how 23andMe can efficiently and cost-effectively deliver its service. Scientists have identified the known variation among individuals, specifically locating in the human genome where a single letter differs from one person to the next.

These one-letter variations are called single nucleotide polymorphisms, or SNPs (pronounced “snips”), and they are associated with differences in everything from the color of our eyes, to our risks for certain health conditions, and information about the makeup of our ancestry.Let’s look at an example of a SNP.Say a certain percentage of people have  a specific stretch of DNA code that reads ATGCCCGT, but everyone else  has the sequence ATGCACGT along that same stretch.

The nucleotide bases come in pairs, so in this case the difference is between whether a person is CC or AC at this position.Image 1Since these two letters are known to vary among individuals, we would call this position in the sequence a SNP. The difference between two people at a single position – whether you are CC or AC in this case  – is also referred to as the genotype for that SNP. Some of those differences may have no effect, some could be beneficial and some could be deleterious.

The benefit or harm of one version or the other can even change depending on one’s environmental surroundings. 23andMe provides individuals with information on hundreds of thousands of these SNPs.To do that, 23andMe first has to extract DNA from saliva submitted by a customer. Once the DNA is extracted, it is amplified many times so that there is enough DNA to analyze. The amplified DNA is then cut into smaller pieces and washed over a microarray chip.

This  genotyping chip contains thousands and thousands of tiny probes that are designed to detect specific bits of DNA. Each probe on the chip contains a bit of DNA that matches a genetic variant of interest. Remember the nucleotide bases always come in pairs, an A always pairs with T, while a G pairs with C.   On the microarray chip, when a piece of DNA finds its complementary probe, it will stick to it.

These probes are triggered to glow in a way that indicates which version of each SNP is present in the sample. That fluorescent signal is read by a computer, and the data is then uploaded to the customer’s 23andMe account.image 2Our customers have the ability to view this raw data in a feature called Browse Raw Data.

Our latest genotyping chip, v4, is unlike any of our previous genotyping platforms. Previous genotyping platforms included standard probes included by Illumina, the manufacturer of the chip, as well as additional probes selected by 23andMe.

The v4 chip, consists of a completely custom panel of probes that were hand picked by our researchers. Although our current genotyping chip contains about half a million SNPs (whereas the entire human genome has around 10 million SNPs), we can learn a lot about the human genome simply by looking at these locations where individual genotypes are known to differ. Full genome sequencing provides information on all 3 billion markers in the entire human genome, however it is difficult to predict when full sequencing will be available at an affordable price point for the general public.

  • 23blog

    Hi Tommy,
    Not at the moment. Hopefully in the long term we will have our pages translated.

  • I purchased a LiveWello kit to upload my raw data, and I am having a problem doing this. Can you help me with this process?

    • 23blog

      You should contact LiveWello about any issues with their features. If you have questions about downloading your raw data from 23andMe. Our Customer Care team can help you out.

  • Could you please help me to download my Raw Data into a text file and store it on my desktop? When I press Download, it is showing up on my Desktop as an HTML file that says I am not logged in. Please help.

    • 23blog

      Hi Brenda,
      Once you download your data it will appear on your computer as a zipped text file. The text file includes the thousands of lines of your genotype call data (your A’s, T’s, C’s and G’s). It can be opened in a text editor like WordPad.

      The download feature requires you to re-enter your account password as well as enter your answer to the secret question that you chose during account setup.

  • I just sent in a request in which I uploaded a copy of what is showing up when I download the raw data in the html file. It does not look like a zipped file to me. Is it? do I simply need to click on that file and log in again? Then how do I transfer this to LiveWello? Will it be obvious, in some way?

    • 23blog

      Hi Brenda,
      So you definitely have downloaded the file?
      If you’ve done that it should appear as a .zip file in your download folder. When you double click that it would unzip and the new file would be a .txt file. If you have that .txt file on your computer you should then be able to take the steps necessary to upload it to any API. I’m not familiar with LiveWello’s process for uploading a file. I would suggest that if the issue pertains to uploading a file to their site, you ask them for help troubleshooting. If it’s an issue about how the file has been downloaded from our site, you should contact our customer care team directly and they can help you. Here’s a link to how to submit a question to them and get some help: https://customercare.23andme.com/hc/en-us/requests/new

      • maryyamada

        Yikes, I’m going to have to read this several times. (or more).

  • Thank you for your response. Yes, I definitely downloaded the file. When I clicked (not re-typed) on the link you listed below https//customercare.23andme.com, it shows that “the page you were looking for does not exist.” Dismay. I don’t know why I am not getting a .zip file when I click to download the Raw Data. Does it matter that I am using an Apple computer rather than a PC?

  • Eeps. I clicked on your link again, and it DID allow me to submit to customer care. Thank you for your assistance.

    • 23blog

      Good luck Brenda. Thanks for sticking with it.

  • maryyamada

    I never could understand genotyping. Thanks for the article.

  • 23blog

    More than 600,000 in the current version of our custom chip, although we are able to impute millions of additional variants.