Category: Genetics

UPDATE:  Genos was bought out by another company…  Good reminder to read through privacy policies!  The company that bought them now owns customer’s data but said they would abide by the Genos privacy policy.  I did ask for my data to be deleted and account to be removed out of an abundance of caution.

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Genos is a fairly new company in the direct-to-consumer genetic sequencing market.  They offer sequencing of the whole exome, instead of just the specific locations that are covered by services such as 23andMe or AncestryDNA. Moreover, they are bringing in research study partners that then will pay their clients for participating in the studies.  It is definitely an interesting business model and one that may end up being a game changer for the genetic sequencing market.

I was intrigued enough to go ahead and try it out and will share what I have learned from the experience. (Yep – this was my birthday present this year!)

First off, sending off the saliva sample was similar to the way 23andMe does it — spit in a tube, register online, and send it off.  Nice and simple process.  The Genos website was easy to use as far as ordering and registering the sample.  The wait time was a little over two months to get the results back, which is a bit longer than 23andMe, but Genos is brand new and was still in beta when I ordered.

When my data finally came in, I was eager to dig in and geek out with it. The Genos website offers a variant viewer that compares my results with ClinVar, which is an NIH-funded database of genetic variants that have been submitted by various sources.  The database marks the variants as pathogenic, benign, or somewhere in between, and it is a good source of information about rare genetic diseases.

While the Genos variant viewer was interesting, there seems to be a lot of information submitted to ClinVar showing a variant to be both benign and pathogenic. And for me, personally, it didn’t show me a lot that I didn’t already know from 23andMe testing. I would imagine that it may be useful for some people in terms of carrying rare genetic diseases.  Keep in mind, though, that Genos is only sequencing the exome.

So what is an exome?  Of the 3 billion plus nucleotide base pairs in our DNA (the A, C, G, and T’s), only a small portion actually make up the coding part of genes.  On each of our 23 pairs of chromosomes, there are sequences that code for genes and then sections that are called non-coding, which have to do RNAs, telomeres, regulatory elements, etc.  Basically, in DNA, genes code for proteins which are made up of amino acids. Most genes have portions of the DNA sequences that code for amino acids (the exons) and then portions that don’t code for part of the protein (introns).  The whole exome is then the sum of all the coding parts of the gene.  While a lot of the serious, rare genetic diseases are a result of variations in the exome, the non-coding parts of our DNA not sequenced by Genos also play a big role in our health as well.

Genos offers a download of your data as a VCF file.  This is where it got complicated for me.  I was under the impression from their website copy that I would be getting 50 million rows of data, and I thought I would need to figure out how to dig through that big of a file with lots of rsIDs and my genotype.  What I downloaded was about 300,000 rows of data with just the HGSV nomenclature and no rsID’s included. Hmmm….  After several emails back and forth with their customer support and bioinformatics department, I finally got a bit of a grasp on what was contained in the VCF file.  Basically, it is everything in my exome that is different from the reference data.  This doesn’t mean that it is everything that is heterozygous or homozygous for the minor allele (a bad assumption on my part), but it is just everything that is different from a reference file.  So I’m going to have to spend some time this summer learning more about bioinformatics and VCF file types in order to get anything out of my whole exome file.  Definitely not an easy way to unlock my curiosity.

The other file that Genos offers for download is a Promethease formatted file.  This allows you to use Promethease (for $5) to compare all of your data against the SNPedia database.  The file is formatted similarly to the raw data file you can download from 23andMe.  Again, I personally learned a lot more from my 23andMe results than I did from my Genos results in Promethease, but your mileage may vary on this as well.

Since I have all my 23andMe data imported into an Excel spreadsheet, I imported in my Genos “Promethease” file to compare the two.  This is where it got interesting for me!

The Genos genotype file (Promethease file) had about 43,000 rsIDs in it, and I compared those to the 600,000+ rsIDs from 23andMe. A few formatting tweaks, merging of the data and I was on my way to seeing how closely the data matched.  Out of the 600,000 data points from 23andMe and 43,000 data points from Genos, only 4,433 were common to both.  (Granted, 23andMe uses “i” numbers instead of rsID’s sometimes, so there could be more in common between the two files than what I could easily count.)  Of those 4433 rsID’s in common, 25 were different between

Of those 4433 rsID’s in common, 25 were different between Genos and 23andMe which is about a 0.5% error/difference rate.  I have my parents’, my husband’s, and my children’s 23andMe data (in a nice spreadsheet, of course), and looking at the inheritance pattern there were 2 spots where 23andMe is probably wrong on my variants (and Genos is probably right).  There were several more spots where Genos was probably wrong and some heterozygous calls that I couldn’t determine which was correct.

I emailed Genos customer support about the differences between the files, and the head of the bioinformatics department pointed me towards a study showing the accuracy of the sequencing.  A 0.5% error rate was actually about average…  This was eye-opening to me.  Even though I knew that there was a possibility for errors, realizing that 1 out of every 200 could be wrong drives home the point that no one should make major health decisions based on this data.

To sum it all up…

• I like the goals of Genos and that they recognize that customers should be compensated for participating in research studies.  This is a big contrast to 23andMe asking customers to give away information for free.
• I personally didn’t find the information received from Genos, though, to be worth the price.   The variant viewer on the Genos website was somewhat interesting, but the information out of ClinVar is too narrow in its scope.  It would be great to have something like the gene lookup function that 23andMe has to really be able to know what your genotype is for a specific rsID without the need to conquer the VCF file format.
• Keeping in mind that Genos is new to the game, things may change on their website and with what they offer to their customers.  Do check with them if you have questions.  Their customer support response sometimes took a day or two, but they were good at patiently answering my many questions.

Someone asked me recently how to download their data from 23andMe.   So, here is a quick tutorial if anyone else is searching for their raw data file on the 23andMe website.

Why download your data? It is yours, and it may be something you need in the future.  23andMe could change their policy on allowing downloads, or they could go out of business at some point.  Seriously – everyone should go ahead and download their genetic data file and keep it in a safe place.

Downloading Your Raw Data from 23andMe

Step 1: Go to www.23andMe.com and log in with your password.

Step 2: On the top navigation bar, put your mouse pointer over the word Tools.  A drop-down appears with a link to go to Browse Raw Data.

Step 3: Click on the Download link.

Step 4: Scroll down to the bottom of the download page (yes, read it as you scroll :-).  There you will click the button to request to download your data.

Step 5:  It takes several minutes for the download to be ready.  23andMe will send you an email, or you can just refresh the download page again in a few minutes.

Step 6: Get geeky with your info and put it into an Excel spreadsheet.

Reading through some Facebook questions the other day, it hit me that most people are not keeping track of their genetic information for themselves.  There are so many recommendation for ‘reports’ that you can order for $19 or $50 or much more.  A lot of these reports just color your SNPs red or green, which isn’t necessarily meaningful. Some polymorphisms will make an impact on your health and some have no impact.  So I’ve decided to explain how I personally keep track of information on my own genes (and for family and friends).

Short answer: I simply created an Excel spreadsheet, imported all of my raw data file, and use a separate sheet to look up my genetic info.

The spreadsheet isn’t beautiful, but it contains way more information than any of the paid reports that I’ve seen.  Plus it has all of my notes that are pertinent just to me! It is important to me that I know the source of the information and to read through studies myself rather than just relying on what someone else might say.  (There is a lot of speculation,  misinformation, and wacky stuff floating around on the internet – especially on Facebook!)

A final advantage of creating your own spreadsheet to keep track of your genetic information is that it is private.  I always worry a little bit about the security of sharing my 23andme data on another website.

Step-By-Step for Excel Gene Report using 23andMe Raw Data

Step 1: Download your raw data file from 23andMe. Log into the 23andMe website and go to the Tools section.  Click on Raw Data, and the click on Download.  That will take you to a page with instructions on how to download the file.  After downloading it, you will need to un-zip the compressed file, and then I really recommend saving it in a place where you won’t lose it (i.e. don’t leave it in your downloads folder!).

Step 2: Open up Excel and start a blank workbook.  Import your raw data file by going to File, Import, and choosing to import a Text File. (Or your version may have a Data tab and an icon for importing Text.)  Find your .txt file that you just downloaded from 23andMe.  It is a “Delimited file” that is tab delimited.  It may take a minute to import all the data since your raw data file is over 600,000 rows.

Step 3: Open a new sheet by clicking on Sheet 2 at the bottom of your Excel screen.  This new sheet is where you will make your genetic ‘report’.

I set up mine to have headings across the top of Gene Name, SNP id, Risk Allele, person’s name (yours!), and Notes.  Here is an example with some made up data:  

Step 4: Here is where the real magic comes in!  For each SNP id and risk allele, your alleles will be looked up and automatically included.

Go ahead and put in some data:   put in MTHFR C677T under your Gene Name column and rs1801133 under your SNPid column.  The risk allele for MTHFR C677T is  A.

Then in the column for your gene data you will use the following formula to look up your information from your raw data sheet.

=VLOOKUP(TRIM($B2),Sheet1!$A$16:$D$610564,4,FALSE)

What this formula does is looks at what is in B2 (the SNP id) and compares it to everything on your raw data sheet (Sheet1) in all of the rows.  Then when it finds a match, it returns your genotype for that SNP id.

Step 5: Add in some more Genes and SNP ids (read the rest of my blog posts to find more), and then copy the formula down under your gene data column by clicking on the little box in the lower right corner of the cell and dragging it down the columns that you want to fill.  (You can copy and paste the normal way as well if you don’t like the ‘fill handle’ shortcut.)

Double check that you have copied correctly by checking that the VLOOKUP formula is always referring to the row that you are on (e.g. $B3).

Also, the “Risk Allele” always needs to be in the same orientation that 23andMe uses (referred to as forward or plus).

Step 6: Finally, add in some color to make it easy to read.  Use whatever color coding system makes sense to you — this is YOUR spreadsheet.  I did end up setting up Conditional Formatting to automatically color code my spreadsheets, but that is a more complicated tutorial for another day.