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. 

Family Tree DNA Will Keep $99 Price for Family Finder

I just received the GREAT news from Max Blankfeld that Family Tree DNA will be able to keep the low and competitive price of $99 for Family Finder:

Family Tree DNA Will Keep Reduced Prices

One month ago Family Tree DNA reduced its Family Finder price to $99 with the promise that if we achieved a minimum volume of orders during our Sizzling Summer Promotion, Illumina would help us keep this price moving forward. We are happy to announce that the genetic genealogy community responded in a big way, and thanks to you we are maintaining the price of the Family Finder test at $99.

We hope that with this price reduction you can reach out to family and friends, so that more and more people can join our growing database and find new matches.

Thank you for your continued support!

Max Blankfeld, Vice-President and COO

http://www.GeneByGene.com

max@genebygene.com

713-868-1438

This development has leveled the playing field for all three companies offering autosomal DNA tests to the genealogy community and allows those who prefer not to receive health results and/or wish to have their DNA sample stored for 25 years to affordably do so. I hope that this will encourage more genealogists to get themselves and their families into the Family Tree DNA Family Finder database. It benefits all of us to have genealogists with well-documented family trees participating in our groundbreaking autosomal DNA research. These price drops are really helping us to get to the critical mass that we need to get the most out of these databases. Recently, I have seen great strides in this regard in my research. Thank you to everyone who ordered tests during this trial run and to FTDNA and Illumina for making this possible.

Family Tree DNA's DNA Day Sale Starts Now!

***UPDATE - THIS SALE HAS BEEN EXTENDED THRU THURSDAY, APRIL 25th***

Just in from Family Tree DNA. (These are really great prices!)

FAMILY TREE DNA ANNOUNCES SPECIAL DNA DAY REDUCED PRICING
••••••••

LOW PRICES ON THESE AND MANY MORE:
Full Mitochondrial Sequence: $189
Family Finder:  $169
Y-DNA + Full Sequence: $358

We are pleased to announce our 2013 DNA DAY Promotion. While the special pricing features all the major tests, we’re placing particular emphasis on the Full Mitochondrial Sequence and Family Finder. We’ll offer Y-DNA upgrades during a Father’s Day sale and will give you those details
at that time. By carefully choosing the sale options and limiting the length of the sale, we will be better able to focus our resources on processing the tests efficiently and avoiding delays in delivering results.

We are proud to announce we have successfully moved our mtDNA Full Sequencing line from Sanger DNA sequencing to what is called Next Generation Sequencing (NGS). This gives us much greater capacity to process tests, to reduce costs without sacrificing quality, and to ensure shorter turnaround times. We must run the entire sequence every time we process an mtDNA full sequence test, even for upgrades. However, in recognition of your prior investment- and National DNA Day – we’re offering our lowest price ever for the FMS and upgrades. Rather than the 8-10 weeks first generation sequencing required, we expect results to be completed within 5-6 weeks. This does depend on the number of orders received though. If their DNA is already at our lab, those who order first may expect even shorter turnaround times. For a limited time we will be selling the FMS for $189 and whether you’ve tested HVR1 or HVR1+2, you’ll be able to upgrade to the Full Sequence for just $129!

In addition, we are also lowering the Family Finder to $169 for this sale! Here is the list of all tests under the promotion:

Full MtDNA Sequence…. $189
Upgrades to FMS….$129
Y-DNA37 (new and add-on)…. $119
Y-DNA67 (new and add-on)…. $199
Y-DNA37 + Full MtDNA Sequence…. $308
Y-DNA12 + FF…. $218
Y-DNA37 + FF…. $288
Y-DNA67 + FF…. $368
Family Finder.... $169
Family Finder + Full MtDNA Sequence…. $358
SuperDNA….$388 (Y-67 + FMS)
Comprehensive DNA…. $557 (Y-67 + FMS + FF)

The sale will begin tonight, April 18th, at 6PM CDT and will conclude at 11:59PM CDT on Monday April 22nd. All orders must be placed and paid for by the end of the sale to receive the promotional price. There will be no need for a coupon - all prices will be automatically adjusted on the website.  Order here.

THANK YOU FOR YOUR CONTINUED SUPPORT
Bennett Greenspan
President
Family Tree DNA

All orders must be placed and paid for by 11:59PM on Monday April 22nd, to receive the promotional rate. As with all promotions, orders need to be placed by the end of the sale and payment must be made by end of this sale.

Family Tree DNA 72 Hour Weekend Sale Starts Now

Family Tree DNA just announced a short 72 hour sale starting now through Sunday night 11:59pm (CDT). Here is the text of the email I received: It seems every time we run a flash sale a few people e-mail us days later that they were traveling, sick or just had not looked at their e-mails in time, so for all of you who want to entice a friend, neighbor or reluctant relative to get involved in Genetic Genealogy here's one more opportunity, but it will last for only 72 hours. We are gearing this sale for newcomers and upgrades by promoting the Family Finder and the Full Mitochondria Sequence (FMS). This sale starts Friday, September 28, at 12:00am and ends Sunday, September 30, at 11:59PM.

New Kits Current Price SALE PRICE Family Finder $289 $199 mtFullSequence $299 $199 Family Finder + mtFullSequence $559 $398 Upgrades Current Price SALE PRICE Family Finder $289 $199 HVR1 to mtFullSequence $269 $199 HVR2 to mtFullSequence $239 $199 mtFullSequence $289 $199

As with all promotions, orders need to be placed by the end of the sale and payment must be made by the end of this sale. Learn More

Adoptee Finds Birth Family at AncestryDNA

After my posts criticizing AncestryDNA for their handling of "Chris and Pat's" matching, it is only fair to report the terrific news that the second adoptee mentioned in my original story (let's call her Jenny) has confirmed that her close match is, indeed, authentic. A few weeks ago "Jenny" reported that she received a match with a predicted first cousin at AncestryDNA. Today we received the news that Jenny has actually found her biological paternal aunt!

At first I thought there was a discrepancy between the prediction and the actual relationship, but after seeing screen grabs from Jenny's account, I realized that Ancestry has two different categories that each include first cousin; one is "Close Family - First Cousin" and the other is "First Cousin - Second Cousin".  Given this opportunity, let's take a look at Ancestry's "First Cousin" categories.

I happen to have a known first cousin in my mother's AncestryDNA account, so I can compare the two categories here. Vi is predicted to be a First Cousin to my mother with a range of 1st Cousin to 2nd Cousin:

My mother's first cousin at AncestryDNA

With this explanation:

Click to Enlarge

Since I have this same cousin available for comparison at 23andMe, I can tell you that she shares 14.5% of my mother which is a bit higher than average. So, AncestryDNA got this right even though Vi and my mom share more than would be expected for a first cousin relationship.

My mother's first cousin at 23andMe

I share a first cousin once-removed relationship with Vi and 7.44% of my DNA, and she correctly falls into the same First to Second Cousin Category for me at AncestryDNA.

There is another category at AncestryDNA that is labeled as Close Family to First Cousin. It looks like this:

With this explanation:

Click to Enlarge

This is the category that the Jenny's match was placed, so in this case AncestryDNA's prediction was also correct.

AncestryDNA has not released their category guidelines, but from this I can deduce approximately what the percentage cut-off must be between the two categories (if they are using the traditional matching process that we are familiar with from 23andMe and Family Tree DNA's Family Finder). An aunt would share approximately 25% of her DNA with her niece, first cousins share approximately 12.5% of their DNA, first cousins once-removed share approximately 6.25% of their DNA and second cousins share approximately 3.125% of their DNA. These are variable numbers which are only an average, so some individuals, like my mom and her cousin Vi, will share more and some will share less than expected. AncestryDNA has apparently taken this into consideration since they correctly placed my mom's first cousin Vi in the lower First Cousin - Second Cousin category instead of the Close Family - First Cousin category. Without more comparisons, it is impossible to accurately guess AncestryDNA's upper end cut-off for this category, but at 23andMe my highest aunt/uncle relationship comparison is 27.88%, while my lowest is 21.14%, so they probably include at least 28% in this category and possibly much higher since the next closest genetic relationship level shares about 50% of their DNA - full siblings. AncestryDNA likely takes additional information into account in their predictions such as longest segment length and how many shared segments, but for general guidelines, the categories possibly look something like this:

Close Family - First Cousin Category        28% - 15% in common
First Cousin - Second Cousin Category     15% -  5% in common

If this is close to their actual thresholds, then the Close Family Category could include half-siblings, grandparents, aunts and uncles (as we have seen in Jenny's case) and possibly great grandparents/first cousins who are on the high end of expected shared DNA.

With all of this analysis, I don't want to get sidetracked from the joy of this story. Jenny is absolutely thrilled to find her paternal birth family and they seem to be thrilled to find her! She is very appreciative of AncestryDNA's part in her discovery and, thanks to that aunt who is a member of Ancestry.com, Jenny already has an extensive genealogy for half for her biological family!

Jenny shared her thoughts with me:

I need to give AncestryDNA some credit, they were 100 percent right on this one. Although I still stand by my opinion that their system needs changes, because there still is no way to know if there are errors...They need to release the raw data, not everyone is going to be as lucky as I was, but I also don't want to discourage people from submitting their DNA.  The more DNA they receive, the better the results I would presume.  They have a great system for the most part, but with no way to interpret it, we have to just have blind faith in Ancestry that our results are correct.

Personally, I am very happy to be able to report this positive flip side to my earlier story because I do not want to discourage anyone from participating in DNA testing. Although not my first choice, with a database that has exceeded 65,000 (judging from recent ID numbers), AncestryDNA is a viable place to search for relatives whether it be for adoption reunification or genealogical purposes. You can bet that we, as a community, will keep badgering the folks at AncestryDNA for our raw data and access to more detailed genetic information, but some will enjoy success with their matching system even as it currently is. In fact, because of their outstanding automated matching combined with their vast collection of already existing family trees, a number of individuals have already reported confirming many common ancestors with their matches at AncestryDNA and, in some cases, broken through decades-old brick walls. These successes could greatly aid in, perhaps, the loftiest dream of our community - to build a universal genetic family tree by "assigning" DNA segments to specific ancestors, but only if AncestryDNA decides to release the genetic data to their customers. Let's keep our fingers crossed that they will soon listen to us, because what a wondrous thing this could be!

[10/26/12: This test is now out of Beta, so you can order it here.]

"Finding Your Roots with Henry Louis Gates Jr." - DNA in The Fourth Episode

Last night PBS aired the fourth episode of Finding Your Roots with Henry Louis Gates Jr. which featured husband and wife Kyra Sedgwick and Kevin Bacon. The episode concentrated on exploring the couple's deep American roots, stretching back to the early days of the Colonies.

Husband and wife Kyra Sedgwick and Kevin Bacon

Unfortunately, there was very little genetic genealogy in this episode. At the very end, Dr. Gates presented Kyra with her DNA results explaining, "Using traditional genealogy, we were able to trace her father's line back hundreds of years...but using DNA Analysis we were able to go even deeper into her past on her mother's line establishing her Jewish ancestry genetically." First Dr. Gates showed Kyra a chart. In editing they inserted a shot of a chart illustrating the path of Y-Chromosome DNA which is passed down from father to son. Since she is a woman and they were discussing her mother's side, I believe that they were actually analyzing her mitochondrial DNA haplogroup which is passed from mother to child. The voiceover said that they were looking deep into the past of her mother's line, so she likely has a mtDNA haplogroup that is associated with Ashkenazi Jews.

Chart from "Finding Your Roots" showing the path of Y-DNA

Then they looked at a chart from 23andMe's Ancestry Finder and Dr. Gates explained, "Here's a graph of your 23 chromosomes and what it says is that 50% of all of your genetic material that they examined traces back to Ashkenazi Jews."  Note that he adds the qualifier "that they examined". This is because the Ancestry Finder feature only reaches conclusions about the portions of your DNA that have people who match it in their system, so most people do not have 100 percent coverage on this tool. Ancestry Finder is based on the answers that your DNA matches provide on the 23andMe survey "Where Are You From?" and, therefore, bases its analysis on the stated birth places of your matches' grandparents. (For more information on this feature, please see the post that I wrote about Ancestry Finder when it was first introduced.) The Ancestry Finder feature allows a user to click a box to see which of their matches have self-identified their grandparents as Ashkenazi Jews. For Kyra, this was apparently the case with approximately 50% of her total matches on Ancestry Finder. Instead of showing a screenshot of the graph of her "23 Chromosomes" which would have illustrated this result, they showed an image of her Ancestry Finder list of matching populations (seen below). This list of matching populations identified by Ancestry Finder also supports Dr. Gates' team's conclusion that Kyra has substantial Ashkenazi Jewish ancestry since the ones at the top of the list are typical in my experience for  those with Jewish ancestry.

Kyra Sedgwick's 23andMe Ancestry Finder from "Finding Your Roots"

At the end of the episode, Dr. Gates revealed to Kyra that her fear of being cousins with her husband Kevin Bacon was confirmed and that she and Kevin are 9th cousins once removed. Although fun for entertainment purposes, in the context of genetics, this is pretty meaningless since chances are that neither of them has any genetic material remaining from their shared ancestor(s). If they were to both test their autosomal DNA at 23andMe or with Family Tree DNA's Family Finder, they would likely not find any significant common DNA between them (unless they have closer yet unidentified shared ancestors). Since Dr. Gates team likely did test them both at, at least, 23andMe, I suspect my assumption is correct. This is because with each successive generation of random autosomal DNA inheritance, the contribution of each ancestor gets broken into smaller and smaller pieces and the majority of our ancestors have "fallen off of our genetic family tree" by the time you reach back past a couple hundred years. (Blaine Bettinger of "The Genetic Genelaogist"explains this concept here.) That is why autosomal DNA tests for genealogy like 23andMe and FTDNA's Family Finder work best for researching more recent ancestry.

I am looking forward to next week's episode with Rick Warren, Angela Buchdahl, and Yasir Qadhi and hope to see more integration of genetic genealogy. In the preview, I caught a glimpse of my friend, 23andMe's geneticist Mike Macpherson (one of the creators of Ancestry Finder). I can't wait to see his appearance on the show!


I have been writing a review of the DNA testing used in each episode:
Week 1 - Episode 1 and Episode 2 - Harry Connick Jr. & Branford Marsalis; Cory A. Booker & John Lewis
Week 2 - Episode 3 - Barbara Walters & Geoffrey Canada