Wednesday, 9 August 2017

23andMe launch a new v5 chip and revise their health and trait offerings in the UK

23andMe have quietly rolled out their new v5 chip. There has not so far been any official announcement from 23andMe, though the news was confirmed yesterday by a moderator in the 23andMe Forums. We believe 23andMe are now using Illumina's new Global Screening Array chip which is already being used by Living DNA. 23andMe were one of the 12 customers who signed up to the GSA in June 2016. They also belong to the Global Screening Array Consortium.

The GSA has 640,000 markers and the ability to include up to 50,000 custom markers. Here is a description of the chip from Illumina:
The Infinium Global Screening Array-24 v1.0 BeadChip combines multi-ethnic genome-wide content, curated clinical research variants, and quality control (QC) markers for precision medicine research. 
The genome-wide content was selected for high imputation accuracy at minor allele frequencies of >1% across all 26 1000 Genomes Project populations. The clinical research content includes variants with established disease associations, relevant pharmacogenomics markers, and curated exonic content based on ClinVar, NHGRI, PharmGKB, and ExAC databases. Quality control content enables sample identification and tracking for large-scale genomics and screening applications.
The full technical specifications for the GSA chip can be found here on the Illumina website.

The Illumina Omniexpress chip, which was previously used by all the genetic genealogy companies, is being phased out, so we are likely to see other companies moving to the GSA in due course. The OmniExpress worked well for European populations but was not so good for other populations. The GSA provides much better global coverage and should improve the results for people with non-European ancestry.

The GSA is designed for imputation. Imputation is the process of inferring the missing markers in a DNA sequence. This can be done by statistical methods because DNA is passed on in chunks, which means that markers travel together. Researchers can use imputation to reconstruct an entire genome sequence, and it provides a much more cost-efficient way of doing large-scale studies. However, I know of no scientific papers which have looked at the efficacy of imputation for cousin matching. The companies will have a significant challenge ahead in the months to come as they adapt to the new chip and test out their imputation pipelines.

Because there are so few overlapping markers between the GSA and the OmniExpress this change will also present problems for companies and third-party websites that accept autosomal DNA transfers. A choice will need to be made as to whether to do comparisons using only the overlapping markers or whether to experiment with imputation. GEDmatch is already experimenting with its new Genesis database, which can now accept GSA transfers. It will be interesting to see what solutions are found by other companies.

Along with the move to the new chip, 23andMe have also changed their product offering in the UK. There has not been any official announcement but as far as I can establish from the archived versions of their British website in the Internet Archive the changeover seems to have occurred some time towards the beginning of May. When the website was archived on 29th April 23andMe were still offering UK customers 100 health and trait reports. They offered 40+ reports for inherited conditions, 40+ drug response reports, 10+ genetic risk factor reports and 40+ trait reports. The genetic risk factor reports including reports for haemophilia and some breast cancer genes (BRCA1 and BRCA 2). A full list of the previously offered health reports can be seen here.
The 23andMe GB home page on 29th April 2107.
The next archived version of the 23andMe GB website dates from 6 May 2017. From that date onwards UK customers have been offered a very much reduced range of health reports. There are now 40+ carrier status reports, 3+ genetic risk reports and 25+ traits and wellness reports. The drug response reports are no longer provided at all, and the breast cancer and haemophilia reports have been dropped. A full list of the new reports offered can be found here. As far as I can establish UK customers now receive exactly the same version of the test as customers in the US, the only difference being that we do not have an option to order an ancestry-only version of the test for half the price.
The 23andMe GB home page on 9th August 2017.

23andMe have slowly been moving their customers over to their new website (otherwise known as The New Experience or TNE for short). My accounts were finally transitioned on 15th June 2017. I understand that all the UK accounts were transitioned at the same time. I believe the transition process is now complete, with the Canadians appearing to be the last people to be transitioned in July.

With the transfer to the new website all our old health reports have been archived. There are no new health reports. Instead there are five ancestry reports, 19 trait reports and 7 "wellness" reports.


I was on holiday in the US when I was transitioned and I initially assumed that the lack of new health reports was because I was accessing the website from the US and not the UK. However, I later established that none of the transitioned accounts in the UK were receiving any new health reports. I wrote to 23andMe customer service to find out why this was the case and received the following message on 10th July:
Per FDA restrictions, newly authorized reports will not be provided to customers genotyped on your current chip version. The conditions covered by our newly authorized reports are addressed by reports in your Reports Archive.

In order to receive the newly authorized reports, you will need to be genotyped again. Upgrades are unavailable at this time. We are currently working on an upgrade policy for our customers and would encourage you to wait for this policy to be finalized. The upgrade policy will allow you to be genotyped on our most up-to-date chip at a discounted rate within the next few months. More information about upgrades will be available soon.
My guess is that 23andMe customers in the UK have been tested on the new v5 chip from May 2017 onwards when the website changed and the number of reports was reduced.

23andMe received authorisation from the FDA in April this year to start offering genetic health risk reports for 10 diseases and conditions. No doubt they are also working towards approval for introducing other reports too. Clearly, in order to get the FDA approval, the reports will need to be validated on the new v5 chip and it's no longer worth their while trying to update and validate the old-style health reports. I can therefore understand the decision to stop offering these reports to existing customers.

tested with 23andMe back in 2010 on the v2 chip. I've never had to pay a subscription or pay for any updates so I've had very good value for money in the last seven years. I will be upgrading to the new chip when it becomes available to existing customers and I shall look forward to receiving all the new reports as and when they become available.

Update 10th August 2017
It has been confirmed in a post by a moderator in the 23andMe Forum that 23andMe are now using the Illumina Global Screening Array. They suggest that with an upgrade to the new chip: “Results shouldn’t change significantly, however, there may be some slight differences in Ancestry Composition, DNA Relatives, and small changes in your haplogroup assignment.”

We are told that 23andMe have updated their phasing algorithms so that “family members can still be phased, even if they are on different chips”.

It appears that the transition to the v5 chip is not yet complete. Here is a further quote from the moderator: “Our labs are currently transitioning to the v5 chip. While transitioning, there may be some overlap between v4 and v5 data being released. Future customers will be genotyped on v5.”

Tuesday, 8 August 2017

MyHeritage acquires Legacy Family Tree and discounts on Legacy webinar subscriptions


It was announced last week that MyHeritage have acquired the Millennia Corporation, the company who produce Legacy Family Tree genealogy desktop software and who also run the popular Legacy Family Tree Webinars.

For further details on this acquisition you can read the statements from MyHeritage and Legacy:
For commentary on the acquisition I recommend reading the following two articles which provide interesting insights and perspectives:
I'm not a Legacy user so I'm not affected by this change. (I use the British family tree program Family Historian which I highly recommend.) However, it will be interesting to see what impact this change has on the genealogy market and how MyHeritage and Legacy move forwards. The increased exposure through the Legacy webinar platform is likely to help MyHeritage improve their share of the DNA testing market.

Most of the Legacy webinars are free to view in the first week but you need to have a subscription to access the webinar archive and some premium webinars. It's also often necessary to have a subscription to access the speakers' handouts. Much of the content up until now has been aimed at US researchers but there have also been other webinars of more general interest. I've enjoyed watching a few webinars about DNA testing, particularly those from Blaine Bettinger and Diahan Southard, who always do an excellent job of explaining complicated science in easy-to-understand language. To celebrate the acquisition there is a special offer on the annual Legacy webinar subscription and it is on sale for just $24.98 (£19) until 13th August, which is 50% off the usual price. I've decided to splash out, as there quite a few webinars I would have liked to have seen that for one reason or another I didn't have time to watch when they first became available.

AncestryDNA hits the five million milestone

Ancestry have announced on their US Facebook page that they now have an astonishing five million AncestryDNA customers. Ancestry passed the four million milestone at the end of April this year and the three million milestone in January. That means they've sold two million tests in the first seven months of 2017. If sales continue at the current rate they will have tested seven million people by the end of the year. Christmas is always the peak selling period so sales could ultimately be much higher than that. How long will it take for the database to grow to 10 million or 20 million?

AncestryDNA do not give breakdowns of sales by country. Their test has been available in the US since May 2012 but only launched in the UK in January 2015. It became available in Australia and New Zealand in May 2015, Canada in June 2015 and 29 other countries in February 2016. I would estimate that about 80% of AncestryDNA's sales are now in the US. It seems likely that a considerable amount of their growth in the last year or so has come from people testing in these new markets.

Sales seem to be particularly strong in the UK, Ireland, Australia and New Zealand. AncestryDNA have been marketing their test extensively in these countries. In the UK, for example, AncestryDNA now sponsor the long-running TV programme Long Lost Family, which regularly attracts around five million viewers. The seventh series is currently being aired on ITV, and AncestryDNA are linking their promotions to the programme. The banner below now appears when you log into your Ancestry account.


The marketing is helping to bring in a new demographic to DNA testing. People are taking a DNA test out of curiosity and not as an aid to genealogical research. However, some of these new people who are testing will start to explore their matches and become interested in family history. This can only be good news for everyone.

Note
Although Ancestry's Facebook page shows that there is a sale on in the US until 15th August, the test does not appear to be on sale in any other country at present.

Further reading
Leah La Perle Larkin has published a blog post with updated figures on the size of the GEDmatch database and an updated graph showing the growth of the autosomal DNA databases. See her article Genealogical database sizes - August 2017 update.

Update
The official AncestryDNA press release can be read here.

Sunday, 6 August 2017

Comparing parent and child matches at AncestryDNA

A number of genetic genealogists have done comparisons of parent and child matches at AncestryDNA to see how many of the smaller matches do not match either parent:

  • Ann Raymont published an article in July 2016 When is a match a false positive? She found that 35.3% of her matches did not match either parent.
  • Blaine Bettinger wrote a blog post on The danger of distant matches back in January this year. He found that 32% of his matches were not shared with either of his parents.
  • Kevin Ireland published his results in an article entitled atDNA case study: two parents and one child. He found that 18.5% of his matches did not match either parent.
  • Karin Lovisa Borgerson has this week published a blog post Baby versus bathwater: distant matches. She found that 17% of her matches were not shared with either parent.
  • I recently tested both of my parents at AncestryDNA and I thought it would be an interesting exercise to do a detailed analysis of my own matches to see how my results compare with the other studies. I used the DNAGedcom Client to download my matches from AncestryDNA. I used the Match-O-Matic tool, which is included with the Client, to analyse my matches. See the methodology section below for details of how the analyses were done.

    My matches at AncestryDNA
    I tested on the AncestryDNA v1 chip in June 2012. I currently have 10,232 matches at AncestryDNA.

    Using the same categories as Blaine Bettinger my matches break down like this:

    Category Number Percentage
    Over 50 cMs 9 0.08%
    25 cMs or more 39 0.38%
    20 cMs or more 71 0.69%
    15 cMs or more 251 2%
    10 cMs or more 1403 14%
    Fewer than 10 cMs 8837 86%
    6-7 cMs 4512 44%

    Two of my matches in the over 50 cMs category are my parents. All the other matches have tested independently at AncestryDNA.

    Sharing with my parents at AncestryDNA
    My parents were tested on the AncestryDNA v2 chip in June 2017

    My dad has 8350 matches at AncestryDNA.

    My mum has 11285 matches at AncestryDNA.

    Here are my findings after comparing my matches with my mum and dad:
    • 3299 (32%) of my 10232 matches are shared with my dad
    • 3276 (32%) of my 10232 matches are shared with mum
    • 20 (0.2%) of my matches appear on the match lists of both my mum and my dad.
    • 3671 (36%) of my matches do not appear on the match lists of either of my parents.
    • Of the 3671 matches which do not match either of my parents 3559 (97%) shared a single DNA segment and 112 (3%) shared 2 segments. Ninety-six (86%) of the two segment matches shared less than 10 cMs, and 16 (14%) shared between 10 and 16 cMs.
    I divided the matches into "bins" to see what the match rate was for different levels of sharing. The results are shown in the table below.

    cM bins Total
    matches
    Total matching
    a parent
    % matching
     a parent
    Total matching
     neither parent
    % matching
     neither parent
    50 cMs + 9 9 100% 0 0%
    40-50 cMs 1 1 100% 0 0%
    30-40 cMs 10 10 100% 0 0%
    20-30 cMs 51 51 100% 0 0%
    19-20 cMs 25 25 100% 0 0%
    18-19 cMs 18 17 94% 1 6%
    17-18 cMs 30 30 100% 0 0%
    16-17 cMs 46 45 98% 1 2%
    15-16 cMs 61 58 95% 3 5%
    14-15 cMs 96 86 90% 10 10%
    13-14 cMs 148 134 91% 14 9%
    12-13 cMs 180 161 89% 19 11%
    11-12 cMs 291 274 94% 17 6%
    10-11 cMs 437 386 88% 51 12%
    9-10 cMs 799 679 85% 120 15%
    8-9 cMs 1275 1001 79% 274 21%
    7-8 cMs 2241 1534 68% 707 32%
    6-7 cMs 4512 2058 46% 2454 54%

    Double matches
    I also took a look at the 20 matches that my parents shared with each other. My parents do not appear as matches to each other and do not have any identifiable common genealogical ancestors. I also checked to see if these shared matches appeared on my match list. Here is the breakdown:

    Match cMs shared
     with Dad 
    cMs shared
     with Mum
    Match to Debbie
    Match 1 8.7576 7.9563 Yes
    Match 2 9.2653 6.984 Yes
    Match 3 9.3549 7.363 No
    Match 4 6.082 7.5295 Yes
    Match 5 6.4811 8.0814 No
    Match 6 9.3519 7.4345 Yes
    Match 7 27.0902 8.1206 No
    Match 8 10.009 14.0302 Yes
    Match 9 6.5761 9.6979 Yes
    Match 10 6.262 7.8819 No
    Match 11 6.4201 7.5106 No
    Match 12 7.9815 6.1787 Yes
    Match 13 9.2775 6.3962 No
    Match 14 11.4808 6.3302 Yes
    Match 15 7.26 6.1234 Yes
    Match 16 6.8033 7.0212 Yes
    Match 17 8.8658 6.2839 Yes
    Match 18 7.1988 6.0201 Yes
    Match 19 6.5682 8.9985 Yes
    Match 20 10.7345 14.5475 Yes

    Discussion
    Although 36% of my matches did not match either of my parents, the headline figure is not as gloomy as it might at first appear. The vast majority of these non-matches were on small segments under 10 cMs, and the lion's share of non-matches were on the very tiny segments under 7 cMs.

    All matches sharing 19 cMs or more were shared with one of my parents so this can be considered my personal safe zone where matches are guaranteed to be valid.

    There were just four out of my 155 matches sharing between 15 and 19 cMs which did not match one of my parents. The largest non-shared match was 18.2 cMs. This means that 87.5% of my matches in this range were valid.

    Below 10 cMs the chance of not sharing a match begins to increase exponentially. With the very smallest matches sharing just 6-7 cMs only 46% matched one of my parents.

    Matches that do not match my parents are either false positives, which means the matches are not real matches, or false negatives, which means that the match is not showing up in the match list of my parent for one reason or another. However, without further investigation it is not possible for me to determine whether these matches are false positives or false negatives. This can only be done by careful chromosome mapping and by testing multiple close family members.

    AncestryDNA use a phased matching technique. Phasing is the process of assigning individual alleles to the maternal and paternal chromosomes. A lack of phasing results in many false matches. These are sometimes known as pseudosegments. For a discussion of the reasons for these false matches see the ISOGG Wiki article on identical by descent. Because AncestryDNA use phasing they are able to deliver matches on smaller segments than the other companies. While phasing provides more accurate matches, the process is not without its problems. One of the limitations is that we are not tested on our whole genome but rather a sampling of markers scattered across our genome. If matching were to be done on the whole genome we would no doubt find that many of our matches are not valid after all. A second problem is that the phasing algorithms are not perfect. Sometimes they break up a longer match into smaller segments. There is also a problem of what are known as phase switch errors, when the phase accidentally switches from the maternal to the paternal chromosome or vice versa.

    I am fortunate that I've been able to test both my parents which allows me to do a sanity check on my matches. However, if you are not able to test your parents you will have no way of knowing which of the small segment matches are likely to be valid. It was also interesting to note that some of my matches were shared by both my parents. If I hadn't tested both my parents or if I'd only tested one of my parents I could easily have been led astray with these matches.

    Matches at Family Tree DNA and 23andMe are not phased so the false match rate is going to be even higher there.

    Even if these small segments are real, the odds are still stacked against the match falling within a genealogical timeframe. We know from computer simulations that over 60% of 10 cM segments are likely to trace back beyond ten generations. This does of course also mean that 40% of 10 cM matches are likely to fall within the last ten generations, but computer simulations have the advantage of working in an idealised world where every segment can be reliably attributed. In real life it is much more complicated and with the current matching algorithms there is an additional risk that these segments will not be accurately identified.

    The genetic genealogy community has known for a long time the problem of using small segments in genealogical research, and my findings simply add to the existing evidence base. I already have 1773 matches at AncestryDNA that share 10 cMs or more. I can still only find genealogical connections with a handful of those matches. There is really no reason to get down in the weeds with these small segments under 10 cMs.

    Methodology
    I am using version 1.5.1.3 of the DNAGedcom Client with a PC running Windows 7. The DNAGedcom Client is a subscription service costing $5 a month. The Match-O-Matic tool is included in the subscription. Match-O-Matic was designed for a Mac but converted to a Windows format by Rob Warthen for use in the DNAGedcom Client. For details of the DNAGedcom Client and Match-O-Matic see the user guide

    I downloaded my match lists into Excel spreadsheets using the DNAGedcom client on 4th and 5th August.

    I used the Match-O-Matic tool provided with the DNAGedcom client to analyse my matches.

    To see how many matches I shared with my parents I used the report labelled Matches in common (matches in both files) [ICW] to combine the match lists for my mum and dad..

    To see how many matches did not appear in either of my matches lists I then used the report labelled Combine files (all matches without duplicates) [ALL]. In order to get the program to work correctly I renamed the output file with the prefix m_.

    I used the report labelled Matches in A that are not in b [ANB] to extract a list of matches that were in my match list but were not in the combined match list of my parents.

    Acknowledgements
    Thank you to Rob Warthen for developing the DNAGedcom Client. Thank you to Don Worth for developing the Match-O-Matic. Thank you to Richard Weiss for advice on using Match-O-Matic.

    Update
    Since publishing my blog post Alex Coles has also done an analysis of her parent and child matches at AncestryDNA. Alex and her parents all tested on the v1 chip. Alex found that 31% of her matches did not match either parent. All the non-matches were below 17 cMs apart from one intriguing outlier. Read Alex's article Imprecise science. Part 1 AncestryDNA on her Winging It blog

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