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Showing posts with label Big Y. Show all posts
Showing posts with label Big Y. Show all posts
Tuesday, 29 July 2014
Family Tree DNA reduce the price of the Big Y test to $595
I wrote at the weekend about the new Y Prime test from Full Genomes which is designed as a competitor to Family Tree DNA's Big Y test. Family Tree DNA have now responded by announcing a permanent reduction in the price of their Big Y test, and they have also introduced a few new features to the Big Y display. Note that FTDNA's Big Y is only available to existing FTDNA customers. It's good to see some healthy competition in the Y-DNA testing market. Here is the text of the e-mail that was sent out to project administrators:
Monday, 9 June 2014
Father's day sale at Family Tree DNA with special prices for Family Finder and the Big Y
Family Tree DNA have announced a sale in honour of Father's Day which in many countries of the world, including the UK and the US, is celebrated on the third Sunday of June. For a limited period from 9th June to 17th June the Family Finder test will be reduced from $99 to just $79 (about £47). As far as I can recall, this is the the lowest ever price for this test. Family Finder is an autosomal DNA test which allows you to find matches with your genetic cousins up to about the fourth or fifth cousin level. If you're not familiar with the Family Finder test see my blog post The new Family Finder test from Family Tree DNA which I wrote when the test was first launched in April 2010. For a practical example of how the test works see my post on My first autosomal DNA success story.
Family Tree DNA are my company of choice for autosomal DNA testing. They are the only one of the big three DNA testing companies to sell their tests worldwide and, more importantly for those of us in the UK, they probably have the highest concentration of autosomal DNA test results from the British Isles, thus maximising your chances of finding a meaningful match. AncestryDNA don't even sell their autosomal product outside the US. 23andMe sell their test in 56 countries, including the UK, but they charge a hefty fee to despatch the kits by courier, which effectively doubles the price of the test. The majority of 23andMe customers have tested for health reasons and are less interested in genealogical research, whereas Family Tree DNA is a dedicated genetic genealogy company. For a comparison of the different autosomal tests see Tim Janzen's autosomal DNA testing comparison chart in the ISOGG Wiki. If you've not already taken the Family Finder test now is your big chance to do so. If you've already tested, you might like to encourage your friends and family to test as well. The Family Finder test works best when you have results from multiple family members, and the more people who participate the more success we will have.
The Big Y test is also included in the FTDNA sale. The Big Y test is an advanced test for people who wish to be involved in the Y-SNP discovery process, and is only available for existing FTDNA customers. See my previous blog post The new Big Y test from Family Tree DNA for further information about this test. If you are interested in taking the Big Y test you should consult with the administrators of your haplogroup project. If you're not already in a project you can find a list of Y-DNA haplogroup projects in the ISOGG Wiki. A new SNP matching feature is to be launched for the Big Y test in the next few weeks which should help with the SNP discovery process. For a comparison of the various Y-SNP tests see the Y-DNA SNP testing comparison chart in the Wiki.
Here is the e-mail that was sent out to Family Tree DNA group administrators. (Note that the dates are in US order with the month followed by the day.)
Family Tree DNA are my company of choice for autosomal DNA testing. They are the only one of the big three DNA testing companies to sell their tests worldwide and, more importantly for those of us in the UK, they probably have the highest concentration of autosomal DNA test results from the British Isles, thus maximising your chances of finding a meaningful match. AncestryDNA don't even sell their autosomal product outside the US. 23andMe sell their test in 56 countries, including the UK, but they charge a hefty fee to despatch the kits by courier, which effectively doubles the price of the test. The majority of 23andMe customers have tested for health reasons and are less interested in genealogical research, whereas Family Tree DNA is a dedicated genetic genealogy company. For a comparison of the different autosomal tests see Tim Janzen's autosomal DNA testing comparison chart in the ISOGG Wiki. If you've not already taken the Family Finder test now is your big chance to do so. If you've already tested, you might like to encourage your friends and family to test as well. The Family Finder test works best when you have results from multiple family members, and the more people who participate the more success we will have.
The Big Y test is also included in the FTDNA sale. The Big Y test is an advanced test for people who wish to be involved in the Y-SNP discovery process, and is only available for existing FTDNA customers. See my previous blog post The new Big Y test from Family Tree DNA for further information about this test. If you are interested in taking the Big Y test you should consult with the administrators of your haplogroup project. If you're not already in a project you can find a list of Y-DNA haplogroup projects in the ISOGG Wiki. A new SNP matching feature is to be launched for the Big Y test in the next few weeks which should help with the SNP discovery process. For a comparison of the various Y-SNP tests see the Y-DNA SNP testing comparison chart in the Wiki.
Here is the e-mail that was sent out to Family Tree DNA group administrators. (Note that the dates are in US order with the month followed by the day.)
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Saturday, 26 April 2014
A new BAM file analysis service from Full Genomes Corporation and a special offer on the FGC test
The following message is posted on behalf of Full Genomes Corporation:
Full Genomes Corporation (FGC) is announcing the official launch of a service to analyze BAM files from Family Tree DNA's Big Y product. The analysis is being launched at a price of $50 per kit. Recently, FGC had offered the Big Y analysis for a limited time, as a beta product, at no charge. FGC will continue to allow individuals to contribute their BAM files to the Full Genomes database without charge, so that their results may be used in kit cross-comparisons. The offering is designed to provide broader access to FGC's proprietary Y chromosome analysis services and to build FGC's database for purposes of kit comparisons.
The analysis will include the same reports as provided to customers of the Full Genomes sequencing product, with the exception of the mitochondrial DNA analysis, which will use the Yoruba reference sequence for Big Y kits. So, the analysis will consider Y-STRs and INDELs, in addition to Y-SNPs. To be clear, however, the results won't be able to achieve the same resolution as the Full Genomes sequencing product due to limitations with the underlying data from the Big Y test.
Interested individuals should first obtain access to their Big Y BAM file by contacting Family Tree DNA customer service. Those interested in ordering analysis can follow the instructions here to set up a Full Genomes account, make payment, and upload their BAM file; analysis will be performed in weekly batches. Those who are only interested in contributing their results to the Full Genomes comparison database may send the download link to fgcfilesharing@gmail.com, while also indicating their interest in donating their results and optionally providing a name (like FTDNA Kit Number) to associate with the results.
According to Dr. Greg Magoon, Y chromosome data analysis consultant for FGC, "I think the FGC analysis will address many of the needs that have been expressed by members of the genetic genealogy community who have been looking at Big Y results in recent weeks. In my view, the main strengths of the FGC analysis include its cross-kit comparisons and its SNP reliability classifications. We have put a lot of R&D into separating the wheat from the chaff to allow customers and researchers to quickly focus on the most reliable, phylogenetically-useful variants. I think the FGC analysis will help to significantly speed the interpretation of results and decrease the burden on busy genetic genealogists."
Separately, FGC is announcing a beta-stage referral program, which will provide customers with access to advanced analyses of their Full Genomes "next-gen" sequencing data. A Full Genomes customer who refers at least three other individuals to order the Full Genomes test will be entitled to a bleeding-edge, advanced analysis of their choosing. Potential analysis options include:
-Remapping of results to the newer, build 38 human genome reference sequence
-Remapping of results with a new and improved alignment algorithm/approach
-Y-STR analysis using a newer, larger STR database
-Phylogenetic analysis for portions of the Y tree
-Variant calling (SNPs and INDELs) for autosomal and X-chromosome data
Interested customers are advised to contact sales@fullgenomes.com to supply documentation of referrals and to discuss custom analysis options.
Dr Magoon said: "From a research perspective, I'm very excited about the potential for the referral program to push the boundaries of Y-chromosome analysis. We've already been able to work with customers on a case-by-case basis to do some very interesting customized analyses with the Full Genomes results, including the identification of large duplications and deletions through copy-number variation (CNV) analysis."
Speaking about FGC's next-gen sequencing test, CEO Justin Loe said: "The FGC Y chromosome product is the most comprehensive in the market today but it is also, as we recognize, expensive for many potential customers. Over the near term, we expect to be able to make this product more affordable. Additionally, with the advent of new sequencing technologies other products will also be offered."
In fact, in honor of DNA Day, Full Genomes is currently offering a limited-time discount of 20% off the normal price for their comprehensive Y chromosome sequencing test (using coupon code "FGCDNA").
Dr Magoon commented: "I think what we're seeing across genetic genealogy is that companies are finding a niche with products focused on particular areas. For example, 23andMe has been a pioneer in autosomal DNA. We have seen that BritainsDNA has been making great advances in developing innovative chip-based tests for Y chromosome (and other) markers. Family Tree DNA has established a leadership role in Y-STRs and in full mitochondrial DNA sequencing. YSEQ, with Dr. Thomas Krahn, is the world leader in developing Y chromosome marker tests using Sanger sequencing. I am very excited to see FGC working hard to establish a similar role here in the field of "next-gen" Y chromosome sequencing."
Related blog posts
- A confusion of SNPs
The analysis will include the same reports as provided to customers of the Full Genomes sequencing product, with the exception of the mitochondrial DNA analysis, which will use the Yoruba reference sequence for Big Y kits. So, the analysis will consider Y-STRs and INDELs, in addition to Y-SNPs. To be clear, however, the results won't be able to achieve the same resolution as the Full Genomes sequencing product due to limitations with the underlying data from the Big Y test.
Interested individuals should first obtain access to their Big Y BAM file by contacting Family Tree DNA customer service. Those interested in ordering analysis can follow the instructions here to set up a Full Genomes account, make payment, and upload their BAM file; analysis will be performed in weekly batches. Those who are only interested in contributing their results to the Full Genomes comparison database may send the download link to fgcfilesharing@gmail.com, while also indicating their interest in donating their results and optionally providing a name (like FTDNA Kit Number) to associate with the results.
According to Dr. Greg Magoon, Y chromosome data analysis consultant for FGC, "I think the FGC analysis will address many of the needs that have been expressed by members of the genetic genealogy community who have been looking at Big Y results in recent weeks. In my view, the main strengths of the FGC analysis include its cross-kit comparisons and its SNP reliability classifications. We have put a lot of R&D into separating the wheat from the chaff to allow customers and researchers to quickly focus on the most reliable, phylogenetically-useful variants. I think the FGC analysis will help to significantly speed the interpretation of results and decrease the burden on busy genetic genealogists."
Separately, FGC is announcing a beta-stage referral program, which will provide customers with access to advanced analyses of their Full Genomes "next-gen" sequencing data. A Full Genomes customer who refers at least three other individuals to order the Full Genomes test will be entitled to a bleeding-edge, advanced analysis of their choosing. Potential analysis options include:
-Remapping of results to the newer, build 38 human genome reference sequence
-Remapping of results with a new and improved alignment algorithm/approach
-Y-STR analysis using a newer, larger STR database
-Phylogenetic analysis for portions of the Y tree
-Variant calling (SNPs and INDELs) for autosomal and X-chromosome data
Interested customers are advised to contact sales@fullgenomes.com to supply documentation of referrals and to discuss custom analysis options.
Dr Magoon said: "From a research perspective, I'm very excited about the potential for the referral program to push the boundaries of Y-chromosome analysis. We've already been able to work with customers on a case-by-case basis to do some very interesting customized analyses with the Full Genomes results, including the identification of large duplications and deletions through copy-number variation (CNV) analysis."
Speaking about FGC's next-gen sequencing test, CEO Justin Loe said: "The FGC Y chromosome product is the most comprehensive in the market today but it is also, as we recognize, expensive for many potential customers. Over the near term, we expect to be able to make this product more affordable. Additionally, with the advent of new sequencing technologies other products will also be offered."
In fact, in honor of DNA Day, Full Genomes is currently offering a limited-time discount of 20% off the normal price for their comprehensive Y chromosome sequencing test (using coupon code "FGCDNA").
Dr Magoon commented: "I think what we're seeing across genetic genealogy is that companies are finding a niche with products focused on particular areas. For example, 23andMe has been a pioneer in autosomal DNA. We have seen that BritainsDNA has been making great advances in developing innovative chip-based tests for Y chromosome (and other) markers. Family Tree DNA has established a leadership role in Y-STRs and in full mitochondrial DNA sequencing. YSEQ, with Dr. Thomas Krahn, is the world leader in developing Y chromosome marker tests using Sanger sequencing. I am very excited to see FGC working hard to establish a similar role here in the field of "next-gen" Y chromosome sequencing."
Related blog posts
- A confusion of SNPs
Saturday, 1 March 2014
The BIG Y roll out – the SNP tsunami is on its way!
Background
There are almost 60 million base pairs in the Y-chromosome but about half of it is full of repeating complexities which have yet to be deciphered. There are only around 20 million or so bases which are good candidates for sequencing.2, 3 The BIG Y test was designed to provide the most information at the most affordable price. The intention is also to provide information in the most clear and easy-to-use way.
There seems to have been some confusion about how much of the Y-chromosome is sequenced for the BIG Y test so I asked Dr Mittelman for clarification. He advised that the test sequences around 13.5 million bases on the Y-chromosome and provides results for between 11.5 and 12.5 million positions. It is not possible to give a precise figure because NGS results vary from person to person. This is an improvement on the spec that was advertised when the pre-sale was announced in November when a figure of 10 million bases was quoted.
When the BIG Y pre-sale was announced the coverage was advertised as 60x (the number refers to the number of times the Illumina machines read the sequence – the more reads the better). The information on the BIG Y FAQ page has since been updated and the coverage is now being advertised as “55x to 80x average coverage”.
The roll out
The BIG Y tests have been processed in the order in which they have been received, but some people had to supply new DNA samples so their tests will take longer. The first 100 results were released on Thursday 27th February, and there will be a gradual roll out of results running through to the end of March. We had been expecting all the BIG Y results to be released on the same day but it now appears that the anticipated tsunami will be more of a steady trickle of waves – a slow-motion tsunami4 – rather than one giant flood of data. The following message is now being displayed on the personal pages of people who are awaiting their results:
"We expect that all samples ordered during the initial sale (last November & December) will be delivered by March 28th. We are processing samples in first come first serve order. If a sample doesn't pass quality control, we will place it in the next set of results to be processed as long as we have enough DNA sample. If we require an additional sample, we will send a new test kit and place the new sample in the first set to be processed when it is returned."My dad is one of the people waiting his results but I did not place the order until the very end of the pre-sale period so his results will probably be amongst the last to be processed. Along with other people who have ordered the BIG Y test I received an e-mail this morning from Nir Leibovich, FTDNA's Chief Business Officer, apologising for the delay. He advised: "The entire FTDNA team has been working very hard over the last few months with high determination and many late nights. Launching a new product is always a challenge with many moving parts, some more predictable than others. Unfortunately we ran into some surprises beyond our control when one of our suppliers ran out of certain reagents we needed for running the Big Y product... We hope you will let the wonderful product we produced make up for delays that were needed to refine it! We have updated expected results dates on customer pages and will work around the clock to beat them." [Click here to read the full text of the e-mail.]
How many BIG Y tests have been ordered?
I asked if we could be given an idea of the number of BIG Y tests ordered. Although a precise figure was not revealed we were told that there had been "thousands" of orders and that "FTDNA have more Y than anyone else". I know that large numbers of orders have gone through some of the haplogroup projects. There have been 149 orders in the R1b-U016 Project alone and around 340 orders in the R1b-L21 Project. If you have ordered the BIG Y test do make sure you join the relevant haplogroup project so that the very helpful and knowledgeable volunteer admins can help you to understand your results. There is a list of Y-DNA haplogroup projects in the ISOGG Wiki:www.isogg.org/wiki/Y-DNA_haplogroup_projects.
What is reported
Screenshots of the user interface and explanations of the various features can be seen on the BIG Y page in the FTDNA Learning Center:
www.familytreedna.com/learn/user-guide/other-test-results/big-y-page
FTDNA have a big internal SNP database with details of 36,562 known SNPs. Customers will be given a list of their results for all the SNPs in the database. They will be told whether they are ancestral or derived for each position, whether or not the SNP is on the tree, the genome reference co-ordinates, their genotype (their DNA letters) and the confidence rating.
There are three confidence levels for the SNP calls. High confidence means that all the reads essentially agree. Medium confidence means that the information looks good but it has to be manually curated. Low confidence indicates noisy data.
NGS coverage varies from person to person but it is expected that results will be provided for between 25,000 to 35,000 known SNPs per person. The amount of overlap with the tests from Full Genomes, Geno 2.0 and Chromo 2 is not yet known, but it is expected that the BIG Y will cover 90% of the SNPs in the Geno 2 and Chromo 2 tests. There are a handful of people in the genetic genealogy community who have tested with all four companies. Some people have also taken the Walk Through the Y test, the previous SNP discovery test from FTDNA which utilised Sanger sequencing. Once the BIG Y results have all been released and compared with the other tests the haplogroup project admins will be able to provide better information on the overlap between all the tests.
Customers will also be given a separate list of novel variants. These are defined as variants which differ from the reference sequence and which are not seen in the FTDNA SNP database. Thankfully the genome reference co-ordinates will be provided which will allow comparisons with SNPs identified in tests from other providers (with the exception of BritainsDNA who have not released the co-ordinates for their new S series SNPs [see my update from 4th March below]). Dr Mittelman does not yet know how many novel SNPs to expect per person. There is currently no function to compare novel variants in the database, but the test is very much a work in progress and he is open to suggestions for new ideas.
Information will not as yet be provided on INDELS (insertions and deletions), but experienced users will be able to extract the information from the raw data.
File formats
Two types of files will be provided: a VCF file and a BED file. These files are not currently available but should be ready for download some time next week.
The VCF (variant call format) file will consist of a list of all the variants identified, tagged by confidence and location. This is essentially a file showing all your differences from the reference sequence. For an explanation of the file format see the paper by Danecek et al (2011).5 A sample VCF file can be found in the 1000 Genomes Wiki:
www.1000genomes.org/wiki/Analysis/Variant%20Call%20Format/vcf-variant-call-format-version-41
The BED file is a text file which will provide a bunch of ranges for all the areas where information is available for which it was possible to make confident calls. This file will cover all the positions that passed quality control. A useful guide to BED files can be found here:
http://genome.ucsc.edu/FAQ/FAQformat.html#format1
Information about the VCF and BED file formats will be added to the BIG Y Learning Center page in due course.
The raw data files in the form of BAM/FASTQ files will also be made available in due course but a decision needs to be made on the best way to provide the data. I imagine that the data will almost certainly be made available in the cloud, perhaps taking advantage of the new Google Genomics service, or another similar application.
Single SNP testing
The value of a DNA test is in the comparison process and the BIG Y test is no exception. It is hoped that large numbers of new SNPs will be discovered, many of which will be in a genealogical time frame. Ideally a paired testing strategy should be adopted with two very distantly related men from the same subclade taking the test. If novel SNPs are found which identify particular family groups then in theory it should be possible to order single SNPs. Single SNPs can be ordered either direct from Family Tree DNA or from Thomas Krahn’s new company YSEQ. The two companies offer a complementary range of SNPs. Single SNPs cost $35 each from YSEQ and $39 each from FTDNA. However, I suspect that if you are able to identify a SNP in the last two hundred years or so that is only likely to be shared by half a dozen men it will not be cost-effective for any company to offer a single SNP test. Much will also depend on the number of new SNPs identified in a given tree. It might well turn out to be more economical for a surname project to club together and pay for BIG Y tests for project members representing branches of the tree that are of particular interest.
There were some misleading reports emanating from the FTDNA group administrators' conference in Houston last November which suggested that FTDNA had an upper limit of 2000 on the number of new SNPs on offer. Dr Mittelman clarifed that there is no limit on the number of new SNPs that can be ordered. There is a limit on the number of SNPs that can be tested at one time on the lab deck and that limit is 2000. FTDNA can in theory calibrate for use as many SNPs as they can order and design but it’s a question of managing the time.
SNP validation
I asked whether it was necessary for SNPs identifed through next-generation sequencing to be validated using Sanger sequencing. Dr Mittelman advised that with high-confidence SNPs the data is very clean and validation is not necessary. Sanger sequencing might be needed for medium- and low-confidence calls where there are flags and not a lot of data. He also advised that next-generation sequencing is being used to validate the SNPs on the new Geno chip.
Poznik et al (2013) (supplementary data) did in fact validate their NGS SNPs using Sanger sequencing and found a concordance rate of 99.92% with just one discordant genotype.2
White paper
Dr Mittelman advised that once all the data has been through quality control FTDNA will then produce a white paper which will provide information on some of the technical details of the test. The paper will cover performance metrics, value proposition, etc, and they also hope to look at mutation rates, something which is of great interest to the genetic genealogy community and a subject of considerable debate and disagreement! The paper should be out in the next four to six weeks or so.
The new Y-tree
BIG Y data is currently being released using the now very out-of-date and somewhat irrelevant 2010 Y-tree. Bennett Greenspan, the Chief Executive Officer of Family Tree DNA, advised in the webinar that they have had teams of people working on the new tree in collaboration with the Genographic Project. The new tree will be fully integrated with Geno 2.0. The tree needs to be ready from both the technical point of view and the graphical interface, and it seems that it is the latter which is proving more problematic. The tree is not dependent on the release of a scientific paper. Bennett advised that it might be ready in the “next several weeks”. When the new tree is finally launched, SNPs from the BIG Y will be automatically mapped on the new tree.
Third-party tools
FTDNA want to encourage people to use third party tools to get more out of their results and to come up with new ways to analyse the data. I have previously written about YFULL, a Russian company which provides a very nice Y-chromosome interpretation service. See my review from November 2013. The service is currently free if you agree to let them have your sequence, but it is expected that they will charge a fee at some point. The Full Genomes Corporation have also indicated that they might be able to analyse BIG Y data though no announcement has yet been made. With the increasing availability of Y-chromosome sequencing data no doubt other tools and analytical services will appear in the future.
Additional questions
After the webinar had finished I realised that there were still some questions that I hadn't asked and David Mittelman kindly provided me with some answers by e-mail.
Q: Are there any plans to provide results for Y-STRs?
A: Big Y does span STRs but that was not the intent of the product. So you can go to the VCF files or the raw data and you will see insertions and deletions at STRs, however, we do not plan to add this to the web page. I would much rather recommend our established and proven STR tests.
Q: Does the BIG Y raw data also include the full mtDNA genome?
A: No, it is comprehensive sequencing of the accessible parts of the Y chromosome. We, as you know, offer full mitochondrial sequencing as a separate product.
Q: Will a list of positive SNP results be posted on the Project SNP pages?
A: Yes, if they are on the tree
Preliminary analysis of BIG Y results
The initial results from the first batch of BIG Y tests were producing an unexpectedly high number of novel variants. Vince Tilroe has analysed some of these results and reports as follows on the U106 mailing list:
It looks like many of the novel variants shared by many Big-Y testees may belong to a particular subclade below R-L20, the haplogroup to which the primary source of the anonymous male donors belongs to, whose sequences were used to build the ChrY reference assembly, and many of those may even be exclusively private to him. Greg Magoon had filtered them out from the 1KGP and FGC reports, but YFull had assigned "Y" identifiers to some of them.
I've compared novel variants from six Big-Y returns belonging to haplogroup R-L51 and below, and have so far identified 56 "novel variants" shared between at least two of them so far, but individual samples only had between 43 and 48 of those. This pretty much cuts the typical true novel variant count in half, leaving a count that is more in line to what was expected for this process.Charles Moore, the U106 admin, has since received confirmation from another group that many of the novel variants are ancestral shared novel SNPs.
Other SNP tests
Full Genomes Corporation is the only other company which currently offers comprehensive Y-chromosome sequencing. Their test is substantially more expensive than the BIG Y but sequences more of the Y-chromosome. When the BIG Y raw data files become available it will be possible to do a comparison of the two tests. For comparisons of the available SNP tests, including the Geno 2.0 and Chromo 2 chip tests, see the SNP testing comparison chart in the ISOGG Wiki.
What are we going to do with all these SNPs?
I wrote in a previous blog post about the confusion of SNPs generated by the various SNP tests offered by the different testing companies. We now have a situation where four companies/organisations (Family Tree DNA/Genographic Project, Full Genomes, BritainsDNA/ScotlandsDNA and YFull) are maintaining their own proprietary SNP databases. There is a great need for an open access independent database of validated SNPs. ISOGG – the International Society of Genetic Genealogy – are probably in the best position to produce such a database, but they also have responsibility for maintaining the Y-SNP tree. The sheer amount of data generated from the next-generation sequencing tests will represent a significant challenge for the volunteer Y-SNP team. I do wonder if the present tree system is actually sustainable and, if in the long run, it might be better to report results as differences from the reference sequence, as is the practice for mitochondrial DNA. Whatever happens, we will have an interesting year ahead of us.
Are you interested in ordering the BIG Y or another SNP test?
My advice for anyone thinking of ordering SNP testing is to be patient and wait for a few months until all the results from the first batches of BIG Y and Full Genomes tests have been analysed and compared. Once this process has been completed we will have a better picture of the new Y-chromosome landscape and the shape of the tree, and it will then be possible to make an informed choice as to which test to purchase. Dr Mittelman advised that there are no immediate plans for another BIG Y sale. At the moment the priority is to bring down the turnaround time for new orders which is currently 8 to 10 weeks.
If you are interested in being involved make sure you join the relevant haplogroup mailing lists and Facebook groups. If you've tested at Family Tree DNA make sure you join the appropriate haplogroup or subclade project. The mailing lists and groups are usually linked from the haplogroup project websites. There is also a list of mailing lists and Facebook groups in the ISOGG Wiki:
www.isogg.org/wiki/Genetic_genealogy_mailing_lists
Further information
There is a set of BIG Y FAQs in the FTDNA Learning Center:
www.familytreedna.com/learn/y-dna-testing/big-y
The BIG Y page in the Learning Center provides screenshots and descriptions of the user interface:
www.familytreedna.com/learn/user-guide/other-test-results/big-y-page
Elise Friedman presented a webinar on 28th February on the subject of "Getting to know BIG Y Results". A recording of the webinar should eventually be made available in the webinar archive in the Learning Center:
www.familytreedna.com/learn/ftdna/webinars
Update 2nd March 2014
The recording of the BIG Y webinar is now available online and can be accessed via this link (free registration required):
https://attendee.gotowebinar.com/recording/4739415541486853122
Update 3rd March 2014
I have put the full text of the letter from Nir Leibovich, in which he apologises for the lack of communication about the expected date of release of BIG Y results, online here. Despite expectations to the contrary, it was never FTDNA's intention to deliver all the results on 28th February. That was the date when the results were expected to start rolling out. It also transpires that there is currently no way for FTDNA to change the expected date on customers' personal pages until the expected date has actually passed.
I've received a number of comments about the problem with reagents which contributed to the delay. Dr David Mittelman has contacted me to clarify the issue:
"We sequence the Y using Illumina HiSeq equipment and we ran out of reagents to do this, and for a period in December and January, Illumina had a back order in place so we could not order more. Illumina filled the orders in the second half of January and we continued our work. Back orders happen and since Illumina is the only game in town, we don’t have other vendors to go to, when Illumina runs out. Of course we are now rolling out samples continuously and each week, in batches. Just like we do for all our products and just like Full Genomes and other companies do."He adds
"In the meantime as more batches complete I am confident people will be thrilled with the data. We were able to deliver better specs than I originally promised and... we will not ship subpar results to anyone. Everyone will get great data."Update 4th March 2014
Dr Jim Wilson of BritainsDNA/ScotlandsDNA has now released a spreadsheet with details of the genome reference co-ordinates for all the Y-SNPs on the Chromo 2 chip. See the following blog post from CeCe Moore for further details and to download the spreadsheet:
- Dr. Jim Wilson and ScotlandsDNA Release Y-SNP Positions for Chromo2
Thomas Krahn has now uploaded the 8000 or so novel markers to Ybrowse. This will allow the genetic genealogy community to cross-check all the new tree branches discovered by Jim Wilson earlier this year. Thomas Krahn has advised that his company YSEQ can design primers for some of the new SNPs as required.
Update 1st April 2014
Although the BIG Y .vcf and .bed files do not include mitochondrial DNA data, it now transpires that mtDNA is included in the BAM files. The mtDNA data can be extracted using third-party tools. For further details see the following blog post from Roberta Estes:
http://dna-explained.com/2014/04/01/mitochondrial-dna-results-from-the-big-y-test
See also Felix Chandrakumar's blog post on the YFull interpretation service which includes a report on the mtDNA data extracted from his BIG Y BAM test:
http://www.fc.id.au/2014/03/yfull-y-chr-sequence-interpretation.html
Update 29th August 2014
Family Tree DNA have published a white paper outlining the methodology used for the test and the analysis.
Footnotes and references
1. For links and resources on next-generation sequencing see the ISOGG Wiki page: www.isogg.org/wiki/Next_generation_sequencing
2. A good description of the Y-chromosome reference sequence is provided by Poznik
et al (2013) Sequencing Y chromosomes resolves discrepancy in time to common ancestor of males versus females. Science 2013 341; 6145: 562-565:
The Y-chromosome reference sequence is 59.36 Mb, but this includes a 30-Mb stretch of constitutive heterochromatin on the q arm, a 3-Mb centromere, 2.65-Mb and 330-kb telomeric pseudoautosomal regions (PAR) that recombine with the X chromosome, and eight smaller gaps.
This effectively leaves
around 22.98 Mb of “assembled reference sequence”. If you can get hold of the
Poznik paper it contains a very nice figure (Figure 1. Callability mask for the Y-chromosome) showing the regions of the Y-chromosome in which reliable genotype
calls can be made.
On a side note, this paper has come in for a lot of criticism, not the least of which is for the authors' mistaken assumption that mitochondrial Eve and Y-chromosomal Adam should be expected to date back to the same time. For a critique of this paper and some useful related diagrams see the three-part series of articles by Melissa Wilson Ayres: Y and mtDNA are not Adam and Eve: Part 1; Y and mtDNA are not Adam and Eve: Part 2 - What it means to be the Most Recent Common Ancestor and Y and mtDNA are not Adam and Eve: Part 3 - Resolving a discrepancy.
3. Further papers of interest are listed on the Y-chromosome
page in the ISOGG Wiki: http://www.isogg.org/wiki/Y_chromosome
4. The term "slow-motion tsunami" was coined by Charles Moore, the administrator of the R1b-U106 project: https://groups.yahoo.com/neo/groups/R1b1c_U106-S21/conversations/messages/21323
5. Danecek P, Auton A, Abecasis G et al (2011). The variant call format and VCFtools. Bioinformatics 27 (15): 2156-2158.
© 2014 Debbie Kennett
4. The term "slow-motion tsunami" was coined by Charles Moore, the administrator of the R1b-U106 project: https://groups.yahoo.com/neo/groups/R1b1c_U106-S21/conversations/messages/21323
5. Danecek P, Auton A, Abecasis G et al (2011). The variant call format and VCFtools. Bioinformatics 27 (15): 2156-2158.
© 2014 Debbie Kennett
Friday, 15 November 2013
A confusion of SNPs
This article is for experienced genetic genealogists and requires a reasonable understanding of SNPs and haplogroups.
The launch of the new Big Y test from Family Tree DNA has brought to light the difficulties in comparing the offerings of the different testing companies. We have a chart in the ISOGG Wiki which compares the various Y-SNP tests on the market but it is clear that we are not always comparing apples with apples. One of the major difficulties relates to the claims by the companies about the number of Y-SNPs on their chip. A SNP is a change or a mutation in the DNA alphabet at a single position on the Y-chromosome (eg, a C changing to a T). There are around 59 million base pairs in the Y-chromosome. However, surprising as it might be in this genomic era, there are still large sections of the Y-chromosome that have not yet been explored. Build 37, the current build of the human genome reference sequence, has only mapped out the positions of around 25 million base pairs – less than half of the Y-chromosome.1 The discovery of new SNPs is therefore limited to the parts of the Y-chromosome that can be sequenced using current technology. These areas represent just over 40% of the Y-chromosome. In theory, therefore, a SNP could be found on any one of the 25 million bases that can be sequenced.
The exact number of SNPs on the Y-chromosome is not yet known. There is no central resource listing all known SNPs because there is fierce competition and the companies are keen to keep knowledge of the SNPs that they have discovered from their competitors for as long as possible. We therefore have some SNPs that are in the public domain, some unpublished SNPs that are known only to Family Tree DNA/the Genographic Project, some SNPs that are known only to Full Genomes Corporation and some SNPs that are known only to BritainsDNA. To make matters worse all three companies use different naming systems for their SNPs. Full Genomes SNPs are prefixed by the letters FG, and BritainsDNA SNPs bear the prefix S. I understand from the reports from the Family Tree DNA 2013 Conference that the Genographic Project will be publishing a paper some time in the New Year with the new 2014 Y-SNP tree. It therefore remains to be seen what naming system they will use for their SNPs. There will undoubtedly be considerable overlap in the SNPs offered by the different testing companies but until they release their data or until we have comparative results available we will not be able to work out which SNPs are equivalent (synonymous) – in other words which SNPs occur at the same position but which have been given different names by different companies. For example U106 and S21 are alternative names for a single SNP which defines one of the major branches of the R1b haplogroup.
The problem is well illustrated by the recent developments in R1b-M222, a subclade which predominates in Ireland and Scotland, and is seen in many of the surnames that are associated with the clans reputed to descend from the semi-legendary Irish historical figure Niall of the Nine Hostages.2 According to the early results from the Chromo 2 testing at BritainsDNA 27 new SNPs have been discovered downstream of M222.3 Yet at the Family Tree DNA Conference last weekend Miguel Vilar from the Genographic Project advised that they have identified 22 SNPS below M222. Do any of the Geno 2.0 SNPs correspond with the SNPs found by BritainsDNA? The answer is we simply do not know. Neither company releases the full raw data that will allow the participant to determine the genome reference position of the SNPs for which he has tested positive so the results from the two companies cannot be compared. Few results are in any case available at present from the Chromo 2 testing. The Genographic Project are presenting the results of their Gathering the Mayo Genes Project at a public event in Castlebar on Sunday so it may be that further information will be forthcoming then.
So where can we find out about SNPs and their position on the Y-DNA haplotree? By far the most important source is the Y-SNP tree maintained by ISOGG - the International Society of Genetic Genealogy. The tree was launched on 10th April 2006. By the end of the year there were 436 SNPs on the tree. By September 2013 there were 3610 SNPs on the ISOGG tree. According to Roberta Estes' report from Day 2 of the FTDNA conference the new 2014 Y-SNP tree, which will be published by the Genographic Project in 2014, will have 6200 SNPS and 1000 branches.4 This effectively doubles the size of the existing tree and will represent a significant workload for the team of volunteer project administrators who maintain the tree.
However, the ISOGG tree only documents the SNPs whose precise location on the Y-haplotree is known – in other words SNPs that define particular branches of the human family tree on the Y-line. There are thousands more known SNPs. For these SNPs we know that a mutation has been found on the Y-chromosome at the position in question but we do not know if it has any phylogenetic significance, that is, if these SNPs define branches on the Y-tree or if they are unique to the individual.
ISOGG have a SNP index that lists not just the SNPs that are on the haplotree but also those which "are or have been under active investigation and consideration for addition to the Y Haplotree." ISOGG further state that the "SNPs listed here are less than 10% of the currently known SNPs". To supplement the SNP index ISOGG member David Reynolds maintains the ISOGG SNP Compendium Spreadsheet. This was last updated about a month ago and contains a list of 47,680 SNPs which have yet to be added to the ISOGG tree and the SNP index. A small minority of these SNPs are alternative names for previously known SNPs that are already on the tree (for example, some S series SNPs correspond with some of the Z series SNPs that have already been placed on the tree). Most of the rest are SNPs whose position on the Y-chromosome is known but where we do not as yet know where they belong on the Y-tree. David Reynolds reported back in September that he had about another 5000 SNPs to process. He is "curating and combining duplicates" as he goes along so it is a time-consuming process.
There are no doubt many more SNPs that are being published in scientific papers and I don't know if anyone in the genetic genealogy community is currently keeping track of these. In one recent paper uploaded to the ArXiv preprint server two Chinese researchers discovered 25,000 new phylogenetically relevant SNPs.5
Let's now have a look at the offerings of the various testing companies in the light of these numbers. I'm discussing the companies in chronological order based on the dates when their tests were launched. Some companies offer chip-based SNP tests. These tests can only test for previously known SNPs, but the companies can customise the chips to include their own proprietary SNPs for investigation. The new gold standard tests are those which use next-generation sequencing technology. These have the potential to discover thousands of new SNPs.
The Geno 2.0 test from the Genographic Project
The Geno 2.0 test from the Genographic Project was launched in July 2012 and was the first chip test to come on the market with a comprehensive panel of Y-SNPs. The Genographic Consortium published a paper earlier this year with all the technical details of their new GenoChip.6 The supplementary data tell us that the Genographic Project started with "a raw SNP candidate database of approximately 27,500 SNPs" though some of these were duplicates. The original target was to produce a chip with 15,000 SNPs but according to the paper the chip includes around 12,000 SNPs. Customers can download a CSV file with a list of the SNPs. There were 12,059 SNPs in the most recent file that I downloaded for one of my project members. The Genographic Project do not currently provide the genome reference positions of the SNPs on their chip, and it seems likely that this information is being withheld pending publication of the 2014 tree.
The Chromo 2 test from BritainsDNA/ScotlandsDNA
The Chromo 2 test from BritainsDNA/ScotlandsDNA was launched in June 2013. It uses a customised Illumina chip which is advertised as "covering over 15,000 Y chromosome markers, carefully selected to be most informative, and as free from duplication as possible". Only a limited number of results have been released from this test so far, but a flood of results is expected in the next couple of weeks. Customers receive an Excel spreadsheet with a list of all the markers that have been tested. In the one spreadsheet that I've seen there was a list of 14,184 SNPs. Of these, 8,682 SNPs had the S prefix. On the current ISOGG 2013 Y-SNP index the S series SNPs stop at S530. In the list of SNPs that I saw there were 8385 S series SNPs with numbers higher than S530. Many of these SNPs will probably define new branches on the Y-tree but many more could simply be alternative names for currently known SNPs. We do know that the BritainsDNA chip includes SNPs found in the Genomes of the Netherlands Project, and also many SNPs that are likely to be informative for people of British descent. However, BritainsDNA, in common with the Genographic Project, do not publish the genome reference positions of their SNPs. Unless they provide ISOGG with the positions of their SNPs we will have no way of knowing where they fit on the tree and which of their SNPs correspond with those identified by other testing companies.
Full Genomes
Full Genomes is a new start-up company which made a quiet entry onto the market some time towards the end of 2012. They only began advertising their services publicly towards the end of March 2013.7 They currently offer the most comprehensive Y-DNA test on the market covering about 20 to 25 million base pairs representing around 42% of the Y-chromosome. Full Genomes claim to cover 47,000 of the known SNPs on the ISOGG tree and in the ISOGG SNP Compendium. This is after removing "ambiguous results, and synonyms from consideration".8 Around 14 million of the SNPs are reported to be within mappable regions. However, their test is also uncovering many new private SNPs which have not as yet been made public, and the number of new SNPs discovered can be expected to rise as more and more people get tested. At present each testee in one of the common haplogroups can probably expect to find between 25 and 40 private high-quality SNPs. Full Genomes make the raw data available in a BAM file so that customers will have access to the genome reference numbers and can check the ISOGG tree for alternative SNP names as and when new SNPs are placed on the tree.
The Big Y test from Family TreeDNA
The new Big Y test from Family Tree DNA was launched at the weekend at Family Tree DNA's Conference. I've provided preliminary details in a previous blog post. As this is a new test, no results are yet available, and proper comparisons with the other available tests cannot be done. The FTDNA FAQs tell us that the test covers "at least 10 million base-pairs of reliably mapped positions of non-recombining Y-Chromosome", though the exact number of base pairs sequenced has not been disclosed. One conference attendee who spoke to the FTDNA staff was told that "the number of bp [base pairs] analysed will be at least 10 million, but could in some samples go up to 12 million".9 FTDNA claim that their test provides more coverage "than any Y-DNA test on the market". However, the test is clearly not quite so comprehensive as the Full Genomes test but it does have the virtue of being considerably cheaper which will make testing multiple people within a single subclade a feasible proposition. Confusingly FTDNA claim that the test will cover "nearly 25,000 known SNPs placing you deep on the haplotree". I can only think they've taken their figure of 25,000 known SNPs from the research into the Geno 2.0 chip and that they are seemingly unaware of the ISOGG SNP Compendium Index which, as discussed above, lists over 47,000 SNPs. If they are covering over 10 million SNPs then they will surely test most of the SNPs in the Compendium. Fortunately FTDNA have confirmed that they will make the raw data in the form of BAM files available to their customers so we will eventually be able to make comparisons.
Is next generation sequencing SNP testing for you?
Next generation sequencing is clearly becoming the gold standard for SNP testing. The Genographic Project have announced that they will be introducing a new test within the next seven to 12 months and I would imagine that their new test will use next generation sequencing. No doubt a rival new NGS test is in the works from BritainsDNA too.
The new next generation sequencing Y-SNP tests do have the potential in the long run to be genealogically relevant. There is supposedly a new SNP roughly every one and a half generations. In other words, if there's no SNP found in a son then there will more than likely be a SNP in the grandson. One day the SNPs will effectively allow us to draw complete trees for Y-lines within a genealogical a timeframe. As with any DNA test, a full Y-chromosome SNP test is only useful if you can compare your results with large numbers of other people so that we can work out the chronological order of the more recent SNPs and establish which ones are unique to specific lineages. With the Full Genomes test people in the common haplogroups are reportedly getting between 25 and 40 private SNPs. I imagine the numbers will be pretty similar for the Big Y test from FTDNA.
The numbers of people taking these tests are still relatively small – probably in the hundreds rather than the thousands. Even at $495 a time large-scale testing within a surname project is not going to be a practical proposition. However, if low-hanging SNPs are found that are specific to particular surname lineages then, if these SNPs are added to the a la carte menu, people could test for these single SNPs at $39 a time. STR markers can be used in combination with SNPs to predict who will be positive for which SNP, but ideally you need to be tested to at least 67 markers to make a confident prediction.
The potential problem is that FTDNA are only likely to want to invest money developing single SNPs if there are a reasonable number of people who would be willing to pay for such a test. The more recent the SNPs the fewer people will share them and consequently there will be less chance of the custom SNP tests being developed. FTDNA also only currently have the capacity to offer an additional 2000 custom SNPs. However, they have indicated that they will be re-introducing some form of static deep clade test, probably in the first quarter of 2014, which will be at a much more affordable price. SNPs found in the first phase of the Big Y testing will be candidates for inclusion on these chips so there is possibly some incentive for selected representatives of the various subclades to be tested to ensure that the key new SNPs are included in these tests. Full Genomes have also indicated that they hope to offer single SNPs, and a more economically priced SNP test, but it remains to be seen what they will offer. At the current prices NGS full Y testing is really only for people who wish to contribute to our scientific knowledge and to help delineate all the branches on the Y-tree. No doubt the costs will come down in time. Perhaps in five years or ten years the full Y test will be the norm but we're not there yet.
If you are interested in SNP testing the choice of testing company will be down to the individual and will depend on your budget and your objectives. The ISOGG SNP Testing Chart in the ISOGG Wiki provides a comparison between all the testing companies and is updated as new information becomes available. There will inevitably be new products coming onto the market in the next year with each new test appearing to have a slight advantage over its competitors until the next big thing comes along. I strongly recommend that you join the relevant haplogroup project. The group administrators are all very knowledgeable and will be able to offer good advice. There is a list of Y-DNA haplogroups in the ISOGG Wiki. Most of the projects have associated mailing lists which are currently buzzing with activity, and these will often be the best source of information and commentary.
The SNP tsunami
The large number of SNPs that will be generated in what has been described as the SNP tsunami will represent a significant challenge for the haplogroup project admins and the citizen scientists who are trying to interpret these data. The new 2014 SNP tree from the Genographic Project, with a mere 6000 or so SNPs, will be something of an irrelevance, and by the time it is published it will be massively out of date, though it will at least lay the foundations for a new nomenclature. The volunteers who maintain the ISOGG tree will have their work cut out to keep up with the new developments. One of the team, David Dowell, has already commented: "It is clear that our processes need to be reorganized and streamlined if we are going to be able to continue to serve the genetic genealogy community and researchers in related disciplines in a timely basis."10
It seems likely that the current confusion will prevail for several months. As one poster on the U106 list has commented, the now infamous quote by Donald Rumsfeld is a very good summary of the current SNP situation:
2. Moore LT, McEvoy B, Cape E et al. A Y-chromosome signature of hegemony in Gaelic Ireland. American Journal of Human Genetics 2006 78(2): 334–338. Note, however, that this study only used 59 low-resolution STR haplotypes, and many people disagree with the conclusions, both in age and origins.
4. Estes R. 2013 Family Tree DNA Conference Day 2. DNAeXplained blog, 12 November 2013.
5. Wang C-C, Li H. Discovery of phylogenetic relevant Y-chromosome variants in 1000 Genomes Project data. ArXiv preprint server. Submitted 24 October 2013.
6. Elhaik E, Greenspan E, Staats S et al. The GenoChip: a new tool for genetic anthropology. Genome Biology and Evolution 2013; 5(5): 1021-31.
7. See the thread entitled Full Y chromosome sequencing: Phase III Pilot on the Anthrogenica Forum.
8. Magoon G. Message posted in the R1b-U06 mailing list, 11 November 2013.
9. See the comment thread in the private ISOGG Facebook group at https://www.facebook.com/groups/isogg/permalink/10152015234637922/.
10. Dowell D. ISOGG group gears up for SNP tsunami. Dr D Digs Up Ancestors blog, 13 November 2013.
11. For the background to the quote see the entry for Donald Rumsfeld at Wikiquote: https://en.wikiquote.org/wiki/Donald_Rumsfeld.
© 2013 Debbie Kennett
The launch of the new Big Y test from Family Tree DNA has brought to light the difficulties in comparing the offerings of the different testing companies. We have a chart in the ISOGG Wiki which compares the various Y-SNP tests on the market but it is clear that we are not always comparing apples with apples. One of the major difficulties relates to the claims by the companies about the number of Y-SNPs on their chip. A SNP is a change or a mutation in the DNA alphabet at a single position on the Y-chromosome (eg, a C changing to a T). There are around 59 million base pairs in the Y-chromosome. However, surprising as it might be in this genomic era, there are still large sections of the Y-chromosome that have not yet been explored. Build 37, the current build of the human genome reference sequence, has only mapped out the positions of around 25 million base pairs – less than half of the Y-chromosome.1 The discovery of new SNPs is therefore limited to the parts of the Y-chromosome that can be sequenced using current technology. These areas represent just over 40% of the Y-chromosome. In theory, therefore, a SNP could be found on any one of the 25 million bases that can be sequenced.
The exact number of SNPs on the Y-chromosome is not yet known. There is no central resource listing all known SNPs because there is fierce competition and the companies are keen to keep knowledge of the SNPs that they have discovered from their competitors for as long as possible. We therefore have some SNPs that are in the public domain, some unpublished SNPs that are known only to Family Tree DNA/the Genographic Project, some SNPs that are known only to Full Genomes Corporation and some SNPs that are known only to BritainsDNA. To make matters worse all three companies use different naming systems for their SNPs. Full Genomes SNPs are prefixed by the letters FG, and BritainsDNA SNPs bear the prefix S. I understand from the reports from the Family Tree DNA 2013 Conference that the Genographic Project will be publishing a paper some time in the New Year with the new 2014 Y-SNP tree. It therefore remains to be seen what naming system they will use for their SNPs. There will undoubtedly be considerable overlap in the SNPs offered by the different testing companies but until they release their data or until we have comparative results available we will not be able to work out which SNPs are equivalent (synonymous) – in other words which SNPs occur at the same position but which have been given different names by different companies. For example U106 and S21 are alternative names for a single SNP which defines one of the major branches of the R1b haplogroup.
The problem is well illustrated by the recent developments in R1b-M222, a subclade which predominates in Ireland and Scotland, and is seen in many of the surnames that are associated with the clans reputed to descend from the semi-legendary Irish historical figure Niall of the Nine Hostages.2 According to the early results from the Chromo 2 testing at BritainsDNA 27 new SNPs have been discovered downstream of M222.3 Yet at the Family Tree DNA Conference last weekend Miguel Vilar from the Genographic Project advised that they have identified 22 SNPS below M222. Do any of the Geno 2.0 SNPs correspond with the SNPs found by BritainsDNA? The answer is we simply do not know. Neither company releases the full raw data that will allow the participant to determine the genome reference position of the SNPs for which he has tested positive so the results from the two companies cannot be compared. Few results are in any case available at present from the Chromo 2 testing. The Genographic Project are presenting the results of their Gathering the Mayo Genes Project at a public event in Castlebar on Sunday so it may be that further information will be forthcoming then.
So where can we find out about SNPs and their position on the Y-DNA haplotree? By far the most important source is the Y-SNP tree maintained by ISOGG - the International Society of Genetic Genealogy. The tree was launched on 10th April 2006. By the end of the year there were 436 SNPs on the tree. By September 2013 there were 3610 SNPs on the ISOGG tree. According to Roberta Estes' report from Day 2 of the FTDNA conference the new 2014 Y-SNP tree, which will be published by the Genographic Project in 2014, will have 6200 SNPS and 1000 branches.4 This effectively doubles the size of the existing tree and will represent a significant workload for the team of volunteer project administrators who maintain the tree.
However, the ISOGG tree only documents the SNPs whose precise location on the Y-haplotree is known – in other words SNPs that define particular branches of the human family tree on the Y-line. There are thousands more known SNPs. For these SNPs we know that a mutation has been found on the Y-chromosome at the position in question but we do not know if it has any phylogenetic significance, that is, if these SNPs define branches on the Y-tree or if they are unique to the individual.
ISOGG have a SNP index that lists not just the SNPs that are on the haplotree but also those which "are or have been under active investigation and consideration for addition to the Y Haplotree." ISOGG further state that the "SNPs listed here are less than 10% of the currently known SNPs". To supplement the SNP index ISOGG member David Reynolds maintains the ISOGG SNP Compendium Spreadsheet. This was last updated about a month ago and contains a list of 47,680 SNPs which have yet to be added to the ISOGG tree and the SNP index. A small minority of these SNPs are alternative names for previously known SNPs that are already on the tree (for example, some S series SNPs correspond with some of the Z series SNPs that have already been placed on the tree). Most of the rest are SNPs whose position on the Y-chromosome is known but where we do not as yet know where they belong on the Y-tree. David Reynolds reported back in September that he had about another 5000 SNPs to process. He is "curating and combining duplicates" as he goes along so it is a time-consuming process.
There are no doubt many more SNPs that are being published in scientific papers and I don't know if anyone in the genetic genealogy community is currently keeping track of these. In one recent paper uploaded to the ArXiv preprint server two Chinese researchers discovered 25,000 new phylogenetically relevant SNPs.5
Let's now have a look at the offerings of the various testing companies in the light of these numbers. I'm discussing the companies in chronological order based on the dates when their tests were launched. Some companies offer chip-based SNP tests. These tests can only test for previously known SNPs, but the companies can customise the chips to include their own proprietary SNPs for investigation. The new gold standard tests are those which use next-generation sequencing technology. These have the potential to discover thousands of new SNPs.
The Geno 2.0 test from the Genographic Project
The Geno 2.0 test from the Genographic Project was launched in July 2012 and was the first chip test to come on the market with a comprehensive panel of Y-SNPs. The Genographic Consortium published a paper earlier this year with all the technical details of their new GenoChip.6 The supplementary data tell us that the Genographic Project started with "a raw SNP candidate database of approximately 27,500 SNPs" though some of these were duplicates. The original target was to produce a chip with 15,000 SNPs but according to the paper the chip includes around 12,000 SNPs. Customers can download a CSV file with a list of the SNPs. There were 12,059 SNPs in the most recent file that I downloaded for one of my project members. The Genographic Project do not currently provide the genome reference positions of the SNPs on their chip, and it seems likely that this information is being withheld pending publication of the 2014 tree.
The Chromo 2 test from BritainsDNA/ScotlandsDNA
The Chromo 2 test from BritainsDNA/ScotlandsDNA was launched in June 2013. It uses a customised Illumina chip which is advertised as "covering over 15,000 Y chromosome markers, carefully selected to be most informative, and as free from duplication as possible". Only a limited number of results have been released from this test so far, but a flood of results is expected in the next couple of weeks. Customers receive an Excel spreadsheet with a list of all the markers that have been tested. In the one spreadsheet that I've seen there was a list of 14,184 SNPs. Of these, 8,682 SNPs had the S prefix. On the current ISOGG 2013 Y-SNP index the S series SNPs stop at S530. In the list of SNPs that I saw there were 8385 S series SNPs with numbers higher than S530. Many of these SNPs will probably define new branches on the Y-tree but many more could simply be alternative names for currently known SNPs. We do know that the BritainsDNA chip includes SNPs found in the Genomes of the Netherlands Project, and also many SNPs that are likely to be informative for people of British descent. However, BritainsDNA, in common with the Genographic Project, do not publish the genome reference positions of their SNPs. Unless they provide ISOGG with the positions of their SNPs we will have no way of knowing where they fit on the tree and which of their SNPs correspond with those identified by other testing companies.
Full Genomes
Full Genomes is a new start-up company which made a quiet entry onto the market some time towards the end of 2012. They only began advertising their services publicly towards the end of March 2013.7 They currently offer the most comprehensive Y-DNA test on the market covering about 20 to 25 million base pairs representing around 42% of the Y-chromosome. Full Genomes claim to cover 47,000 of the known SNPs on the ISOGG tree and in the ISOGG SNP Compendium. This is after removing "ambiguous results, and synonyms from consideration".8 Around 14 million of the SNPs are reported to be within mappable regions. However, their test is also uncovering many new private SNPs which have not as yet been made public, and the number of new SNPs discovered can be expected to rise as more and more people get tested. At present each testee in one of the common haplogroups can probably expect to find between 25 and 40 private high-quality SNPs. Full Genomes make the raw data available in a BAM file so that customers will have access to the genome reference numbers and can check the ISOGG tree for alternative SNP names as and when new SNPs are placed on the tree.
The Big Y test from Family TreeDNA
The new Big Y test from Family Tree DNA was launched at the weekend at Family Tree DNA's Conference. I've provided preliminary details in a previous blog post. As this is a new test, no results are yet available, and proper comparisons with the other available tests cannot be done. The FTDNA FAQs tell us that the test covers "at least 10 million base-pairs of reliably mapped positions of non-recombining Y-Chromosome", though the exact number of base pairs sequenced has not been disclosed. One conference attendee who spoke to the FTDNA staff was told that "the number of bp [base pairs] analysed will be at least 10 million, but could in some samples go up to 12 million".9 FTDNA claim that their test provides more coverage "than any Y-DNA test on the market". However, the test is clearly not quite so comprehensive as the Full Genomes test but it does have the virtue of being considerably cheaper which will make testing multiple people within a single subclade a feasible proposition. Confusingly FTDNA claim that the test will cover "nearly 25,000 known SNPs placing you deep on the haplotree". I can only think they've taken their figure of 25,000 known SNPs from the research into the Geno 2.0 chip and that they are seemingly unaware of the ISOGG SNP Compendium Index which, as discussed above, lists over 47,000 SNPs. If they are covering over 10 million SNPs then they will surely test most of the SNPs in the Compendium. Fortunately FTDNA have confirmed that they will make the raw data in the form of BAM files available to their customers so we will eventually be able to make comparisons.
Is next generation sequencing SNP testing for you?
Next generation sequencing is clearly becoming the gold standard for SNP testing. The Genographic Project have announced that they will be introducing a new test within the next seven to 12 months and I would imagine that their new test will use next generation sequencing. No doubt a rival new NGS test is in the works from BritainsDNA too.
The new next generation sequencing Y-SNP tests do have the potential in the long run to be genealogically relevant. There is supposedly a new SNP roughly every one and a half generations. In other words, if there's no SNP found in a son then there will more than likely be a SNP in the grandson. One day the SNPs will effectively allow us to draw complete trees for Y-lines within a genealogical a timeframe. As with any DNA test, a full Y-chromosome SNP test is only useful if you can compare your results with large numbers of other people so that we can work out the chronological order of the more recent SNPs and establish which ones are unique to specific lineages. With the Full Genomes test people in the common haplogroups are reportedly getting between 25 and 40 private SNPs. I imagine the numbers will be pretty similar for the Big Y test from FTDNA.
The numbers of people taking these tests are still relatively small – probably in the hundreds rather than the thousands. Even at $495 a time large-scale testing within a surname project is not going to be a practical proposition. However, if low-hanging SNPs are found that are specific to particular surname lineages then, if these SNPs are added to the a la carte menu, people could test for these single SNPs at $39 a time. STR markers can be used in combination with SNPs to predict who will be positive for which SNP, but ideally you need to be tested to at least 67 markers to make a confident prediction.
The potential problem is that FTDNA are only likely to want to invest money developing single SNPs if there are a reasonable number of people who would be willing to pay for such a test. The more recent the SNPs the fewer people will share them and consequently there will be less chance of the custom SNP tests being developed. FTDNA also only currently have the capacity to offer an additional 2000 custom SNPs. However, they have indicated that they will be re-introducing some form of static deep clade test, probably in the first quarter of 2014, which will be at a much more affordable price. SNPs found in the first phase of the Big Y testing will be candidates for inclusion on these chips so there is possibly some incentive for selected representatives of the various subclades to be tested to ensure that the key new SNPs are included in these tests. Full Genomes have also indicated that they hope to offer single SNPs, and a more economically priced SNP test, but it remains to be seen what they will offer. At the current prices NGS full Y testing is really only for people who wish to contribute to our scientific knowledge and to help delineate all the branches on the Y-tree. No doubt the costs will come down in time. Perhaps in five years or ten years the full Y test will be the norm but we're not there yet.
If you are interested in SNP testing the choice of testing company will be down to the individual and will depend on your budget and your objectives. The ISOGG SNP Testing Chart in the ISOGG Wiki provides a comparison between all the testing companies and is updated as new information becomes available. There will inevitably be new products coming onto the market in the next year with each new test appearing to have a slight advantage over its competitors until the next big thing comes along. I strongly recommend that you join the relevant haplogroup project. The group administrators are all very knowledgeable and will be able to offer good advice. There is a list of Y-DNA haplogroups in the ISOGG Wiki. Most of the projects have associated mailing lists which are currently buzzing with activity, and these will often be the best source of information and commentary.
The SNP tsunami
The large number of SNPs that will be generated in what has been described as the SNP tsunami will represent a significant challenge for the haplogroup project admins and the citizen scientists who are trying to interpret these data. The new 2014 SNP tree from the Genographic Project, with a mere 6000 or so SNPs, will be something of an irrelevance, and by the time it is published it will be massively out of date, though it will at least lay the foundations for a new nomenclature. The volunteers who maintain the ISOGG tree will have their work cut out to keep up with the new developments. One of the team, David Dowell, has already commented: "It is clear that our processes need to be reorganized and streamlined if we are going to be able to continue to serve the genetic genealogy community and researchers in related disciplines in a timely basis."10
It seems likely that the current confusion will prevail for several months. As one poster on the U106 list has commented, the now infamous quote by Donald Rumsfeld is a very good summary of the current SNP situation:
"There are known knowns; there are things we know that we know.There will be confusion, there will be chaos and there will be competition in the coming months, but from this confusion, chaos and competition many important new discoveries will emerge. I predict that as far as Y-chromosome research is concerned 2014 will be the Year of the SNP.
There are known unknowns; that is to say, there are things that we now know we don't know.
But there are also unknown unknowns – there are things we do not know we don't know."11
Updates
Vince Tilroe advises in a comment on Roberta Estes' blog that the 1.5 Y-SNPs per generation was based on the hypothetical presumption that "the entire 60 megabases [60 million bases] of the Y-chromosome could be sequenced. This is not the case by any means, and consequently a more realistic expectation should be closer to 1 Y-SNP per every 4 to 6 generations". Preliminary results from the Full Genomes testing suggest that there is around one Y-SNP every 3 to 4 generations.
Jim Wilson, the Chief Scientist from BritainsDNA, has provided a list of equivalent SNP names for some of the SNPs on the Chromo 2 chip. He has also advised that in due course he will be sharing the genome co-ordinates to allow comparisons with comprehensive Y-chromosome sequences. See CeCe Moore's blog post A list of alternate names for the Y-SNPs from BritainsDNA's Chromo 2 test for further details.
See also
- A simplified Y-tree and a common standard for Y-DNA haplogroup and SNP nomenclature
- The Y-chromosome sequence interpretation service from YFull
- YSEQ.net - a new company offering a single SNP testing service
References and notes
1. For further information see the ISOGG Wiki article on the Y-chromosome:
www.isogg.org/wiki/Y_chromosomeVince Tilroe advises in a comment on Roberta Estes' blog that the 1.5 Y-SNPs per generation was based on the hypothetical presumption that "the entire 60 megabases [60 million bases] of the Y-chromosome could be sequenced. This is not the case by any means, and consequently a more realistic expectation should be closer to 1 Y-SNP per every 4 to 6 generations". Preliminary results from the Full Genomes testing suggest that there is around one Y-SNP every 3 to 4 generations.
Jim Wilson, the Chief Scientist from BritainsDNA, has provided a list of equivalent SNP names for some of the SNPs on the Chromo 2 chip. He has also advised that in due course he will be sharing the genome co-ordinates to allow comparisons with comprehensive Y-chromosome sequences. See CeCe Moore's blog post A list of alternate names for the Y-SNPs from BritainsDNA's Chromo 2 test for further details.
See also
- A simplified Y-tree and a common standard for Y-DNA haplogroup and SNP nomenclature
- The Y-chromosome sequence interpretation service from YFull
- YSEQ.net - a new company offering a single SNP testing service
References and notes
2. Moore LT, McEvoy B, Cape E et al. A Y-chromosome signature of hegemony in Gaelic Ireland. American Journal of Human Genetics 2006 78(2): 334–338. Note, however, that this study only used 59 low-resolution STR haplotypes, and many people disagree with the conclusions, both in age and origins.
4. Estes R. 2013 Family Tree DNA Conference Day 2. DNAeXplained blog, 12 November 2013.
5. Wang C-C, Li H. Discovery of phylogenetic relevant Y-chromosome variants in 1000 Genomes Project data. ArXiv preprint server. Submitted 24 October 2013.
6. Elhaik E, Greenspan E, Staats S et al. The GenoChip: a new tool for genetic anthropology. Genome Biology and Evolution 2013; 5(5): 1021-31.
7. See the thread entitled Full Y chromosome sequencing: Phase III Pilot on the Anthrogenica Forum.
8. Magoon G. Message posted in the R1b-U06 mailing list, 11 November 2013.
9. See the comment thread in the private ISOGG Facebook group at https://www.facebook.com/groups/isogg/permalink/10152015234637922/.
10. Dowell D. ISOGG group gears up for SNP tsunami. Dr D Digs Up Ancestors blog, 13 November 2013.
11. For the background to the quote see the entry for Donald Rumsfeld at Wikiquote: https://en.wikiquote.org/wiki/Donald_Rumsfeld.
© 2013 Debbie Kennett
Saturday, 9 November 2013
The new Big Y Test from Family Tree DNA
Family Tree DNA have just announced at their conference the introduction of a new Y-chromosome DNA test to be known as the Big Y. The new test uses next generation sequencing technology which is much more reliable for the Y-chromosome than the chip testing used for the Geno 2.0 test from the Genographic Project and the Chromo 2 test from BritainsDNA. The Big Y is intended as a replacement for the Walk through the Y test which used the slower and much more expensive Sanger sequencing technology.
The Big Y test covers 10 million base pairs. It will provide results for almost 25,000 of the known Y-SNPs. However the exciting part is that this test can also be used for SNP discovery, opening up the tantalising possibility of finding SNPs that will prove to be unique to a particular surname lineage or an individual branch of a family tree.
The introductory price of the new test is $499 (£311). The selling price from 1st December will be $695 (£434). The test currently only seems to be available to existing customers, but it may that the FTDNA home page hasn't yet been updated. There is now a new splash page on the personal pages of male FTDNA customers.
People who have ordered the old Walk through the Y test will receive a voucher giving them an additional $50 off the cost of the new test. The new voucher (coupon) will be available on personal pages from Monday.
No doubt further information will be forthcoming in due course from the people who have attended the conference. It has been possible to pick up quite a bit of the news from the conference tweets (search on Twitter using the hashtag #FTDNA2013).
Details of all the other currently available SNP tests can be found on the ISOGG Y-SNP testing comparison chart. This will now need to be updated to include details of the new Big Y test.
In other news from the conference it would appear that the Genographic Project will be introducing a new Geno test within the next seven to 12 months. It may be that the next Geno test will also use next generation sequencing technology.
Updates
A set of FAQs on the Big Y test are now available on the FTDNA website at: https://www.familytreedna.com/learn/y-dna-testing/big-y/
The ISOGG Y-SNP testing comparison chart in the ISOGG Wiki has now been updated to incorporate details of the new Big Y test.
Roberta Estes has advised on her blog that results from the Big Y will be delivered in 10-12 weeks and the results will be accompanied by comparison tools. See her blog post here.
Jennifer Zinck has provided a very nice detailed summary of the first day of the FTDNA conference with further information on the talk on next generation sequencing by David Mittelman, FTDNA's new Chief Scientific Officer, in which the new Big Y test was announced. Click here to read Jennifer's blog post.
CeCe Moore has blogged briefly about the Big Y test. Most importantly she has received confirmation from David Mittelman of Family Tree DNA that Big Y customers will be able to download their raw data files on request.
See my blog post on The Family Tree DNA Conference 2013 for a compilation of all the blog posts and other coverage from the conference.
Related blog posts
- The Big Y roll out - the SNP tsunami is on its way!
- A confusion of SNPs
- The Y-chromosome interpretation service from YFull.com
The Big Y test covers 10 million base pairs. It will provide results for almost 25,000 of the known Y-SNPs. However the exciting part is that this test can also be used for SNP discovery, opening up the tantalising possibility of finding SNPs that will prove to be unique to a particular surname lineage or an individual branch of a family tree.
The introductory price of the new test is $499 (£311). The selling price from 1st December will be $695 (£434). The test currently only seems to be available to existing customers, but it may that the FTDNA home page hasn't yet been updated. There is now a new splash page on the personal pages of male FTDNA customers.
No doubt further information will be forthcoming in due course from the people who have attended the conference. It has been possible to pick up quite a bit of the news from the conference tweets (search on Twitter using the hashtag #FTDNA2013).
Details of all the other currently available SNP tests can be found on the ISOGG Y-SNP testing comparison chart. This will now need to be updated to include details of the new Big Y test.
In other news from the conference it would appear that the Genographic Project will be introducing a new Geno test within the next seven to 12 months. It may be that the next Geno test will also use next generation sequencing technology.
Updates
A set of FAQs on the Big Y test are now available on the FTDNA website at: https://www.familytreedna.com/learn/y-dna-testing/big-y/
The ISOGG Y-SNP testing comparison chart in the ISOGG Wiki has now been updated to incorporate details of the new Big Y test.
Roberta Estes has advised on her blog that results from the Big Y will be delivered in 10-12 weeks and the results will be accompanied by comparison tools. See her blog post here.
Jennifer Zinck has provided a very nice detailed summary of the first day of the FTDNA conference with further information on the talk on next generation sequencing by David Mittelman, FTDNA's new Chief Scientific Officer, in which the new Big Y test was announced. Click here to read Jennifer's blog post.
CeCe Moore has blogged briefly about the Big Y test. Most importantly she has received confirmation from David Mittelman of Family Tree DNA that Big Y customers will be able to download their raw data files on request.
See my blog post on The Family Tree DNA Conference 2013 for a compilation of all the blog posts and other coverage from the conference.
Related blog posts
- The Big Y roll out - the SNP tsunami is on its way!
- A confusion of SNPs
- The Y-chromosome interpretation service from YFull.com
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