23andMe Releases a Sample of Their New V4 File: First Look and Analysis

23andMe has released access to a sample file of their new v4 chip. This is a 100% custom chip with hand-selected SNPs. In a departure from the other two companies offering autosomal DNA testing to the genealogy community, they are now using the Illumina iSelect chip as the foundation instead of the Illumina OmniExpress chip. On the new v4 chip, the total number of autosomal DNA and X DNA SNPs has decreased substantially, while the total number of mtDNA SNP and Y-SNPs has increased.

Since I heard about this new chip, I have been concerned about the impact it will have on the genetic genealogy community and, particularly, on the compatibility with 3rd party uploads and tools. If 23andMe customers are unable to take advantage of the extremely beneficial opportunity to upload their data into Family Tree DNA's Family Finder database and to make use of the wonderful tools at GEDmatch, that would be a huge loss for all of us. It would also be a shame if the usefulness of the Y-SNPs and mtDNA SNPs tested by 23andMe is reduced for our community. To try to determine if this will be the case, Dr. Tim Janzen has helped me to analyze the new file overall and Larry Vick has specifically analyzed the Y-SNPs.

The v4 chip currently has just over 602,000 total SNPs versus 967,000 total SNPs on the v3 chip. This chip is not as robust as the chip previously used by 23andMe or the chips used by Family Tree DNA and AncestryDNA for the autosomal and X-SNPs.This is of great concern, but 23andMe has stated that they plan to impute a large number of SNP allele values from our results (see comments at http://blog.23andme.com/news/23andmes-new-custom-chip/), so hopefully Family Tree DNA and citizen scientists will be able to do the same to extract the most utility and compatibility from this platform. I am continually surprised and amazed by the resourcefulness of our community, so I am hopefully optimistic.

This change in platforms was intended to help the company ramp up their processing capacity in conjunction with their massive marketing campaign to acquire one million customers and beyond.  (They can run 24 samples on each v4 chip at once instead of 8 on each of the v3 chips.) Especially in light of 23andMe's recent decision to provide ancestry-related interpretation and raw data exclusively, the v4 chip does not appear to be a beneficial development. In fact, it may result in additional loss of sales. Currently, the genetic genealogy and the DNAAdoption communities generally recommend first testing at 23andMe and then transferring the raw data into FTDNA's Family Finder database in order to be in two databases at a reduced price. If it turns out that FTDNA is unable to continue to accept 23andMe transfers, these recommendations will likely change. Loss of compatibility with Gedmatch would also have a very detrimental effect on the utility for those using the data for genealogical and admixture research.

The following analysis is in depth and intended for those who want the specific details of the changes. Instructions to download the v4 file will follow the analysis.
 
First let's look at the Y-SNPs.

Larry Vick tells us:
I compared my Y-SNP file I downloaded on 14 Aug 2012 to the Y-SNP file I downloaded today to see if my current file has any changes. There weren't any.  I then compared the (v4) file for Greg MENDEL that I downloaded today to a v3 file I downloaded for a friend (CRL) on 21 Mar 2013.

There are 2,329 Y-SNPs in the Greg MENDEL v4 file. CRL had 1,766 Y-SNPs in his v3 file. So the v4 file has 562 more SNPs than CRL's v3 file. Looking at the SNPs, there were 446 in CRL's v3 file that were not in the MENDEL v4 file. There were 1,009 in the MENDEL v4 file that weren't in the CRL v3 file. Of the 446 in the CRL v3 file that weren't in the MENDEL v4 file, 314 were no calls.

Of the 1,009 in the MENDEL v4 file that weren't in CRL's v3 file, 295 were no calls. When I compared the 1,009 in the MENDEL v4 file to my file I downloaded today, 494 were not in my file (although they could have been in past downloads but were removed prior to today's download). I have SNPs from v1, v2, and v3. Of the 515 that were in my file, 99 were no calls.

I compared the 494 that were not in my file to Adriano's file in the Y-Chromosome Comparison Project, and 268 were in his file. All but one of those 268 had i prefixes for the reference sequence number.

I then compared the 226 that weren't in Adriano's file to the ISOGG Y-SNP Compendium by position number (build 37), and 200 were in the ISOGG file. I created a list of those 200 with the first note field. The 26 that weren't in the ISOGG file included the one SNP with an rs number (rs5603911). The MENDEL file had 46 no calls for the 200 SNPs in the ISOGG file. All but one of the 226 that weren't in Adriano's file had i prefix reference sequence numbers.


Now let's look at the overall composition of the new v4 chip as compared to the other platforms.

Tim reviewed the v4 file and compared it to v2, v3, and FF files. The following are some general statistics on which he based his analysis.

atDNA SNPs
v2: 
561,846 atDNA SNPs in 23andMe v2 data in a 2009 download.
515 i atDNA SNPs in 23andMe v2 data in a 2009 download.
556,787 atDNA SNPs in 23andMe v2 data in a fresh download.
758 i atDNA SNPs in 23andMe v2 data in a fresh download.

v3:
930,381 atDNA SNPs in 23andMe v3 data in a fresh download.
7,455 i atDNA SNPs in 23andMe v3 data in a fresh download.

v4:
577,382 atDNA SNPs in 23andMe v4 data.
41,855 i atDNA SNPs in 23andMe v4 data.

Family Finder:
708,092 atDNA SNPs in Family Finder data in general, but a fresh download only had 707,269 SNPs in it.


Y-SNPs
v2:
1880 Y SNPs in 23andMe v2 data in a fresh download. Of these 213 are i SNPs.

v3:
1766 Y SNPs in 23andMe v3 data in a fresh download. Of these 232 are i SNPs.

v4:
2329 Y SNPs in 23andMe v4 data. Of these 526 are i SNPs.


X-SNPs
v2:
13,876 X SNPs in 23andMe v2 data in a 2009 download. Of these 19 are i SNPs.
13,828 X SNPs in 23andMe v2 data in a fresh download. Of these 96 are i SNPs.

v3:
26,007 X SNPs in 23andMe v3 data in a fresh download. Of these 1006 are i SNPs.

v4:
19,487 X SNPs in 23andMe v4 data in a fresh download. Of these 4227 are i SNPs.

Family Finder:
18,022 X SNPs in Family Finder build 37 data in a fresh download.


mtDNA
v2:
2019 mtDNA SNPs in 23andMe v2 data in a fresh download. Of these 1572 are i SNPs.

v3:
2459 mtDNA SNPs in 23andMe v3 data in a fresh download. Of these 2016 are i SNPs.

v4:
3154 mtDNA SNPs in 23andMe v4 data. Of these 2681 are i SNPs.


Here are his comparisons between the various platforms.

atDNA:

• 453,854 atDNA SNPs in 23andMe v4 data are also found in 23andMe v2 data in a 2009 download. Of these SNPs, 419 are i SNPs. 

• 453,357 atDNA SNPs in 23andMe v4 data that are also found in 23andMe v2 data in a fresh download. Of these SNPs, 546 are i SNPs. 

• 509,630 atDNA SNPs in 23andMe v4 data that are also found in 23andMe v3 data in a fresh download. Of these SNPs, 6153 are i SNPs. 

• 304,864 atDNA SNPs in 23andMe v4 data that have rs numbers are also found in Family Finder in a fresh download. 

• I then checked the 41,855 i atDNA SNPs in 23andMe v4 data and checked for matching positions in the Family Finder data. I found that there were 2556 i atDNA SNPs in 23andMe v4 data that had matching positions in the Family Finder data.

• Assuming that all of those matching positions correspond with the same SNP in the Family Finder data, there are a maximum of 307,420 atDNA SNPs in 23andMe v4 data that are also found in Family Finder in a fresh download. 

Y-SNPs:

• 979 Y DNA SNPs in 23andMe v4 data that are also found in 23andMe v2 data in a fresh download. 

• 1320 Y DNA SNPs in 23andMe v4 data that are also found in 23andMe v3 data in a fresh download.

• This means that there are 1009 Y SNPs found on the v4 chip that aren’t found on the v3 chip. 

• There are 563 more Y SNPs in v4 data than in v3 data. 

X-SNPs:

• 11,070 X SNPs in 23andMe v4 data that are also found in 23andMe v2 data in a fresh download. 

• 11,009 X SNPs in 23andMe v4 data that are also found in 23andMe v2 data in a 2009 download. 

• 14,437 X SNPs in 23andMe v4 data that are also found in 23andMe v3 data in a fresh download. 

• 7,513 X DNA SNPs in 23andMe v4 data that are also found in Family Finder in a fresh download.

mtDNA:

• 1698 mtDNA SNPs in 23andMe v4 data that are also found in 23andMe v2 data in a fresh download. 

• 2208 mtDNA SNPs in 23andMe v4 data that are also found in 23andMe v3 data in a fresh download. 

• This means that there are 946 mtDNA SNPs found on the v4 chip that aren’t found on the v3 chip. 

Tim's preliminary conclusions
The fact that there are only 307,420 atDNA SNPs in 23andMe v4 data that are also found in Family Finder is highly concerning. The specificity of matches when comparing v4 data to FF or AncestryDNA data will be significantly reduced in projects such as my Mennonite autosomal project. At DNA SNP coverage for the overlapping SNPs between v4 data compared to FF or AncestryDNA data will only be about 44 SNPs per cM. I don’t know if FTDNA and GEDmatch will be able to allow imports of 23andMe v4 data. The fact that there are about 130,000 more atDNA SNPs in a Family Finder dataset than in v4 and the fact that v4 data won’t be readily uploadable to GEDmatch is forcing me to rethink 23andMe as my primary testing lab for distant relatives.


Third Parties and Download
My sincere hope is that Family Tree DNA and GEDmatch are able to adjust their systems to work with this new data from 23andMe. As soon as I hear anything, I will be sure and report it.

If you are interested in analyzing the file yourself and you have a 23andMe account, these are the directions for downloading the sample v4 file from 23andMe:

Enable the Mendel family in your account here:
https://www.23andme.com/user/edit/examples/

Then select Greg Mendel's raw data file from the drop-down list here:
https://www.23andme.com/you/download/

This file will probably still change slightly as they complete their validation process, but it should be pretty close to what we will start to see for new customers at 23andMe in the coming weeks.

Please let me know what you think. I am especially interested to hear analysis from the citizen scientists and the creators of our community's third party features. 

"Your Genetic Genealogist" Appointed to Lead 23andMe's Ancestry Ambassador Group

As some of you may have already heard, I was chosen to lead the new Ancestry Ambassador Group at 23andMe. You can read the full announcement on the Spittoon here. I am delighted to have this opportunity to work closely with 23andMe and the outstanding panel members: Dr. Ann Turner, Larry Vick, Dr. Tim Janzen, Andrea Badger and Shannon Christmas, to further the interests of the genetic genealogy community and to promote autosomal DNA testing for genealogy. In our extensive discussions, both Anne Wojcicki and Mike Macpherson have already proven to be very interested in and committed to improving 23andMe's ancestry product and demonstrating to the genealogy community that they value our business. I am very excited about the future of the genealogy customer and ancestry related products at 23andMe.

I do want to assure my readers that I will continue to function as an objective reporter of genetic genealogy related news and a supporter of all companies who serve our community well. I accepted this volunteer position as a means of promoting genetic genealogy and assuring that genealogists' interests are in the forefront of 23andMe's priorities, however this appointment does not mean that I will cease to support other deserving companies in the DNA testing world. Specifically, I am and will continue to be a big fan and supporter of Family Tree DNA. I believe in encouraging people to test, regardless of which company they are using as long as that company delivers a valuable product. I believe in the greater good of promoting this industry, educating and influencing the consumer to participate. This is where I direct my efforts and my passion. I will continue to criticize and praise whenever I feel it is called for, but will always offer solutions when I can in an effort to minimize public backlash that can only hinder the furtherance of our avocation. I invite all of you to do the same.

Since this new position is intended to represent you, my readers and the genetic genealogy community, I would like to receive feedback on what you would like to see at 23andMe in 2012. What improvements, changes, additions would make you a happier customer, a happier genetic genealogist? I have already started a thread in this regard in the 23andMe community forum, but since not everyone participates there, I would welcome comments and ideas here as well. You can also email me privately at the address listed here on my blog. I look forward to hearing your thoughts. Thanks for your readership and participation.


[Disclosure - my company StudioINTV has an existing production agreement with FTDNA that has no bearing on the opinions I express. I also receive a small commission from FTDNA on non-sale orders through my affiliate link, which I use to fund DNA tests. I am currently serving in a volunteer advisory position for 23andMe, for which I may receive a small number of 23andMe kits for my DNA research.  Any opinions that I express here on my blog are my own and do not reflect those of management at either company.  I receive no other compensation in relation to any of the companies or products referenced in my blog.]

Petition urging 23andMe to reconsider their new unpopular subscription policy

Ten days ago I wrote a post about 23andMe's change in policy regarding their customers' access to the genetic-data-based information in their accounts, such as Relative Finder and health reports, after subscription expirations. As expected, this new policy has proven to be extremely unpopular with the genetic genealogy community.  Although I have had some direct communication with senior management at 23andMe, there has, so far, not been any public statement from the company addressing this issue. I am cautiously optimistic that once the holidays are over and things return to normal at 23andMe, there will be a satisfactory outcome to the community's concerns.

In the meantime, the highly respected genetic genealogist and well-known 23andMe customer Larry Vick has created a petition to make sure this issue continues to get the attention it deserves until 23andMe reaches a critical decision about their company's future relationship with the genealogy community. I think we all recognize and appreciate the extremely valuable contributions 23andMe has made to our hobby thus far and very much hope that this issue can be resolved to everyone's satisfaction. It saddens me to read on various forums statements such as "No one in the genetic genealogy community recommends 23andMe any longer." (Dec 22, 2011 - The Norway DNA Project Facebook page). As Dr. Ann Turner recently wrote on 23andMe's forums, echoing many of our thoughts, "I hope 23andMe's revolutionary contribution is not forgotten in the midst of this debacle."

If you are concerned about this issue, please sign the petition here.

Let's hope the New Year brings a positive resolution to this unfortunate turn of events for 23andMe and all of us.