The updated mtDNA tree at Family Tree DNA and an upgrade sale

Family Tree DNA have finally updated the mitochondrial DNA haplogroup assignments for all their customers to Build 17, the latest version of the mtDNA tree. The mtDNA tree is documented by scientists on the Phylotree website. Build 17 of the mtDNA was introduced in February 2016, but until this week FTDNA were using Build 14, which dates back to April 2012, so this update is long overdue. Here is what FTDNA have said about the upgrade in an e-mail to group administrators:

You or your members may have received an email about the update of the mitochondrial DNA database from Build 14 to Build 17, which is the most recent phylogenetic build for mtDNA. This update has been in the works for several months while the scientific team tested and verified the programming and results. We were able to release it this week, so some of you may have seen a change to your mtDNA haplogroup. 

To give you an idea of the scope of this project, Build 14 was based on the analysis of 8,216 modern mitogenomes, while Build 17 was designed using 24,275 mtDNA sequences - almost three times as much information! Build 17 increased to 5437 nodes from 3550 in Build 14, an increase of 1887 haplogroups. Obviously, the update provides a much finer resolution in terms of haplogroup assignment. 

In a very few cases haplogroups may have reverted to a higher branch on the tree. Usually, this is because in Build 14, some of the branches of the tree were predicted, not confirmed. The additional sequences added between Build 14 and Build 17 did not provide supporting data to justify their existence, so these branches have been removed.

What this means in practice is that some people who have taken a full mitochondrial sequence (FMS) test with Family Tree DNA will now find that they have extra letters and numbers in their haplogroup name reflecting the latest discoveries in mtDNA research. For example if you were previously a U4a1a you might learn that you are now either a U4a1a1, a U4a1a2 or a U4a1a3. This is because, as more and more full sequences have become available, it is possible to identify new subclades or branches on the tree.

You can see an updated list of the mtDNA haplogroup-defining mutations on the FTDNA website. Not all subclades have been updated this time but it is always possible your subclade could be refined the next time the tree is updated.

To see where you belong on the mtDNA tree go to the Phylotree website and navigate to your branch of the tree. In the screenshot from Phylotree below you can see the three new daughter clades of U4a1a. Next to the subclade names there is a list of the mutations that define these subclades. The letter and number codes on the far right represent the GenBank IDs of the sequences that were used to define these new subclades.

For a sequence to be used to build the tree it has to be published in the GenBank database. Sequences appearing in scientific papers are uploaded to GenBank on publication. In addition, many Family Tree DNA customers have uploaded their sequences to GenBank so that they can contribute their results to science. If your sequence is used to identify a new subclade you might have the honour of having your sequence listed as one of the two references for that subclade. You might even find that your sequence gets used in a scientific paper! My own personal mtDNA sequence has already appeared in two scientific papers to date.

If you are interested in uploading your mtDNA sequence to GenBank you can find further information on the ISOGG Wiki page on GenBank. 

It's important to remember that you will share your mtDNA sequence with your siblings, your mother, and any cousins who descend in an all-female line from your matrilineal ancestors. There are 37 genes in the mtDNA molecule and in some cases people will have mutations that have medical significance so any mutation that potentially affects you will also affect your other matrilineal relatives. It's very rare to find such mutations but it's always a good idea to get your sequence checked out before sharing it publicly. If you are technically minded you can look up your own mutations on Mitomap. Alternatively you can order a custom mtDNA report from Dr Ann Turner for a small and very reasonable fee. I ordered a report for myself and I can highly recommend this service. 

If you want to find out more about your haplogroup have a look at Rebekah Canada's wonderful Encyclopedia of mtDNA Origins. If you type in the name of your subclade you can pull up a list of all the sequences in your subclade on GenBank and in the Genographic Project database together with a list of relevant publications from the scientific literature, and an estimate of the age of your subclade.

There are some cases where the haplogroup names have not yet been updated. We have a few examples in the mtDNA Haplogroup U4 Project. These have occurred where the subclade-defining mutation is an insertion or deletion. An example of an insertion is 965.2C. This means that, in comparison to the reference sequence, the person has two extra Cs at position 965. An example of a deletion is 301-  or T310d. The way the deletion is reported depends on which reference sequence is being used  – the revised Cambridge Reference Sequence or the Reconstructed Sapiens Reference Sequence. What this deletion means is that there is a letter T in the reference sequence but this letter T is not present in the person who has tested. The FTDNA algorithms currently seem to be unable to handle these insertions and deletions but hopefully this will be sorted out in due course.

In the meantime if you want to check your own haplogroup assignment you can use James Lick's mtHap tool, which is equipped to handle insertions and deletions. It's also a good idea to join the relevant mtDNA Haplogroup Project. Some of the volunteer haplogroup project admins will be able to check the haplogroup assignment for you.

FMS upgrade sale

To coincide with the update to the mtDNA tree FTDNA have announced an upgrade sale. For the next week only you can upgrade to the full sequence from HVR1 or HVR1+HVR2 for just $99. You will only get the detailed haplogroup assignment with the full sequence test. The FMS upgrade is particularly useful if you have a lot of matches at the lower testing levels. mtDNA can also be used at FTDNA in combination with autosomal DNA testing to rule matches in or out on the matriline. Remember too that FTDNA is the only company where you can use your mtDNA results for genealogical matching purposes.They have the world's largest database of full mitochondrial sequences. As of today's date there are 99,847 FMS records in their database. It's only a matter of time before the 100,000 milestone is reached.

BritainsDNA, The Times and Prince William – the perils of publication by press release

The news of Prince William’s Indian DNA was featured in a number of newspapers around the world on Friday. The Daily Mail reported that “DNA testing has revealed that Prince William will become the first British monarch of Indian ancestry”. The Times clearly considered the story so momentous that it devoted most of its front page to the news and also carried a huge spread across pages four and five. Prince William was also the subject of a somewhat gushing editorial marvelling at “the power of science in the age of genetics to illuminate our history” and extolling the virtues of genetic genealogy which “can solve personal mysteries by linking individuals to vast extended families they did not know they had”.¹

The Times is normally regarded as one of the more serious "quality" newspapers in the UK. It was therefore surprising to see a seemingly trivial story more suited to the pages of a family history magazine receiving such prominent and extensive coverage. Furthermore, the story was prominently linked to a readers' offer for the commercial genetic ancestry company BritainsDNA (which also trades as ScotlandsDNA, IrelandsDNA and YorkshiresDNA), who had very conveniently arranged for their new Chromo 2 test to be launched to coincide with the publication of The Times feature. A large box that was to all intents and purposes part of the editorial content on page four of The Times invited readers to discover their "ancient history" with BritainsDNA. As a Times+ subscriber I was advised that I could order a "free upgrade package worth £65" if I ordered a test from BritainsDNA.

The DNA tests for the research were said to have been carried out by Jim Wilson, "a genetics expert at the University of Edinburgh and BritainsDNA". The Times did not clarify that Jim Wilson is a Director of the Moffat Partnership, the name by which BritainsDNA is registered at Companies House, and that he therefore has a direct financial interest in the company.² It is also not clear whether the research was done by Jim Wilson in his capacity as a director of BritainsDNA or as part of his job as Senior Lecturer in Population and Disease Genetics at the University of Edinburgh. Somewhat surprisingly, The Times made no attempt to seek comments on the story from any other expert geneticists for the sake of balance. Nor indeed did any of the other newspapers.

The results of scientific research are usually published in peer-reviewed scientific journals. The peer-review process is particularly important for science because it helps to filter out unreliable research and it also ensures that the full methodology and supplementary information are published with the paper so that the results can be scrutinised and verified by other researchers. The Times makes no mention of a forthcoming paper in a scientific journal, and it would therefore appear that the research is based solely on information given to The Times by BritainsDNA.  The fact that the researchers have bypassed the peer review process and published their results in such an unorthodox way means that there are many questions about the research which have not been answered. The company have a history of making claims in the media and to date none of their research has appeared in a scientific journal. This affair also raises serious questions about the judgement of The Times who have effectively provided an extended advertorial for a commercial company purely on the strength of research that has only been published in a press release.

mtDNA results
The royal ancestor at the centre of the Indian DNA story is a lady by the name of Eliza Kewark, who is the great-great-great-great-great-grandmother of Prince William and Prince Harry. Eliza lived in Surat in the Indian state of Gujarat, but she is usually described in family records as Armenian. To determine the mitochondrial DNA haplogroup (branch of the human mtDNA tree) of Eliza Kewark mtDNA testing was done on two of Prince William's cousins who are direct descendants of Eliza on the direct maternal line. mtDNA is passed on by a mother to her children, but while males inherit their mtDNA from their mother they cannot pass it on to the next generation. As Princes William and Harry and their mother Princess Diana are also direct matriline descendants of Eliza Kewark it can therefore be safely inferred that they would share the same mtDNA haplogroup as their cousins, provided of course that the genealogical research is correct and that there were no hidden adoptions in the family tree.

The Times article does not reveal the level of mitochondrial DNA testing that was performed on Prince William's cousins. However, as BritainsDNA are claiming credit for the research we can only assume that they used their own chip for the tests. The standard BritainsDNA mtDNA test looks at around 300 mtDNA SNPs (markers), while their newly launched Chromo 2 test covers just over 3000 SNPs. mtDNA researchers now prefer to test the full mtDNA genome (all 16569 base pairs). While a well selected panel of mtDNA SNPs is usually sufficient to confirm the base haplogroup we would be more confident of the haplogroup prediction if the results had been made publicly available so that they could be independently verified.

BritainsDNA have confidently claimed their research "confirms… that the mtDNA of Eliza Kewark of Surat was of Indian heritage"³ which led The Times to proclaim that "the Duke of Cambridge will be Britain’s first king to have proven Indian ancestry". An examination of the evidence in the public domain reveals that this claim is something of an exaggeration.

Eliza Kewark’s inferred mtDNA haplogroup is R30b, which is said be incredibly rare, and is certainly not a haplogroup that one would expect to find in a person of British origin. However, this finding is consistent with the genealogical research, and a non-British haplogroup is only to be expected. The question then arises as to whether the haplogroup is one which is indicative of Indian or Armenian ancestry. According to The Times: “Comparison with databases of more than 65,000 individuals from around the world showed that only 14 examples of R30b have been reported, 13 of whom were Indian and one Nepalese. The other related branches, R30a and R30*, are also entirely South Asian.” The databases that were searched have not been revealed but I would imagine that searches have been done in Genbank, mtDNACommunity and Mitosearch. All these public databases are heavily biased and are dominated by people of Western European origin, who tend to be the most active genetic genealogists. GenBank, for example, currently has around 18,000 full mtDNA sequences, with almost 40% of these having been provided by customers of the commercial genetic genealogy company Family Tree DNA.

Clearly, to test the hypothesis that Eliza’s maternal line is from India and not from Armenia it would be necessary to test a sufficiently large sample of people of documented Armenian and Indian origin to determine with reasonable confidence that R30b is only found in India and is absent in Armenia. As far as can be ascertained from the scant details available such research does not appear to have been done. The situation is further complicated by the fact that the Armenians have had colonies in India since the sixteenth century⁴ with one such colony, as reported in The Times, having been in Surat:

"There had been a thriving Armenian trading community in Surat since the 17th century and there was some inter-marriage with the local population. When Theodore [Forbes] met Eliza it was common for British men to begin relationships with Indian women and to have children, even if they already had a family back in Britain.

Susan Harvard, who has been researching Eliza and Theodore’s relationship for almost 30 years, believes that the couple were married in the Armenian church in Surat in early 1812, shortly before he was posted to Mocha in current-day Yemen. However, it may not have been legally recognised.”

There is very little in the scientific literature on haplogroup R30b. It was first discovered by Palanichamy et al in 2004.⁵ Chaubey et al surveyed around 12,000 mtDNAs from across India as part of an investigation into the phylogeography of mtDNA haplogroup R7 in the Indian peninsula and briefly discussed R30:

"Haplogroup R30 splits into two subclades R30a and R30b, the former supported by ten coding region substitutions and the latter by 24 coding and control region mutations. Similarly, in haplogroup R31 a new subclade R31a can be distinguished by 17 control and coding region mutations. Coalescent estimates suggest an ancient branching pattern in hgs R30 and R31, dating back almost to the earliest diversification of the superhaplogroup R itself. This most probably occurred soon after the out of Africa dispersals into the Indian subcontinent."⁶

I have only been able to find one paper which sampled mtDNA from Armenia. Harutyunyan, Khudoyan and Yepiskoposyan took samples from 741 self-identified Armenian males in four regional areas of the country. A further 94 samples were collected from the Armenian community of London.⁷ However, the researchers do not appear to have published the sequences or the haplogroups. They only sequenced the hypervariable region and did not test any coding region SNPs. It is common to find people with identical HVR1 sequences who are in completely different haplogroups. (Note, however, that population geneticists are asking different questions from genetic genealogists and for their purposes it is the relationship between the tree and population history which is important rather than a well-resolved mtDNA genealogy.)

BritainsDNA claim that R30b is rare in India and that only 0.3% of Indian people have this "lineage", though the source of this statement is not given. The fact that R30b is rare even in India makes the need for comprehensive sampling even more important. India has a population of around 1.2 billion and Armenia has a population of over three million, yet we have just a few thousand samples to represent the potentially huge genetic diversity of India, and just a few hundred samples to represent the population of Armenia. If one were to claim at least 10:1 support in favour of an Indian versus an Armenian origin then it would be necessary to test thousands of Armenians to establish that the frequency of R30b in Armenia is significantly less than 0.03%.

The BritainsDNA researchers have brought to light some interesting examples of a rare mtDNA haplogroup. However, there is no proof that Eliza Kewark's maternal line is from India, Armenia or indeed any other country. It is clear that R30b has a very ancient origin and it could, therefore, potentially have a very wide geographical spread. As we have seen there are simply not enough samples available from these regions of the world to draw any firm conclusions.

Autosomal DNA results
The BritainsDNA researchers did further tests on Prince William's cousins using autosomal DNA. These tests show that the cousins were "about 0.3 per cent and 0.8 per cent South Asian, made up of three different blocks of South Asian DNA in each of their genomes, while all the rest was European in origin". They claim that "This provides independent genetic evidence corroborating the mtDNA work" but the evidence is in fact very weak.

There is little information provided about the methodology. As BritainsDNA are claiming the credit for doing the testing I would have thought that they would have used their own chip for the tests. Their new "All my Ancestry" test uses 250,000 autosomal SNPs. Yet, in an article entitled "A royal revelation" on the BritainsDNA website we are told that the researchers read "over 700,000 markers scattered across the genome of Princess Diana's matrilineal cousins". The technical details therefore remain a mystery. We don't know which reference populations were used and which software tools were deployed to calculate the ethnicity percentages. It's common to get conflicting DNA ethnicity results when testing with different companies. However, the experience from the commercial autosomal tests on the market suggests that they are usually adequate to detect inter-continental differences so we can perhaps give BritainsDNA the benefit of the doubt and assume that the South Asian ancestry detected is genuine and not noise.

We inherit a random mix of autosomal DNA from all our ancestors and it is not easy to determine which ancestor contributed which particular segment of DNA. It can be done by a combination of phasing and triangulation if you test enough family members, but it is a very difficult, expensive and labour-intensive process. As Razib Khan has pointed out, it is in fact quite likely that Prince William has no Indian ancestry at all on his autosomal genome.⁸ Genetic ancestors begin to drop off our DNA tree very rapidly and the chances of inheriting a segment of DNA from a specific great-great-great-great-great-grandparent are very slim indeed. The problem has been nicely summarised by Luke Jostins:

The probability of having DNA from all of your genealogical ancestors at a particular generation becomes vanishingly small very rapidly; there is a 99.6% chance that you will have DNA from all of your 16 great-great grandparents, only a 54% of sharing DNA with all 32 of your G-G-G grandparents, and a 0.01% chance for your 64 G-G-G-G grandparents.⁹

It is also important to research the family trees of the two cousins on all their family lines to help to eliminate the possibility that the Asian percentages might have come from ancestors on another part of the tree. Many British people have ancestors who lived and worked in India, and it's quite possible that some people will have multiple ancestors of Indian origin on their tree. As BritainsDNA have not published the details of their genealogical research we do not know if this possibility has been ruled out.

Far from corroborating the mtDNA research the limited autosomal DNA results that have been released to the public provide more questions than answers.

Public invasion of genetic privacy?
Other commentators have cautioned about the ethical implications of revealing the mtDNA haplogroup of a public figure without consent.^{10, 11, 12, 13} This was not something that had occurred to me when I read the story and I am still undecided on the issue. While the haplogroup does not reveal any personal information it is possible that some people will receive DNA results that challenge their views of their identity. It is only common courtesy to ask permission before publishing information about living people, whether they are a celebrity, a member of the Royal Family or just an ordinary individual. It is a debate that we clearly should be having, though a wide consultation would be needed to reach some consensus. The situation is only likely to become more complicated in the future when full mitochondrial sequence testing becomes the norm for genealogy purposes. The full sequence test can sometimes reveal medically informative mutations, and it would be highly unethical to reveal such associations by inference and without consent.

Conclusion
In the last few days we have seen an uncomfortable blurring of the boundaries between academic research and a commercial venture. A genetic ancestry company which claims to be “closely involved in scientific research” has once again failed to follow the standard scientific protocols and has published its research in a press release rather than a peer-reviewed journal. A respected UK national newspaper has compromised its integrity by publishing an advertorial in support of a commercial PR campaign.^{14, 15} We have learnt that Princess Diana, Prince William and Prince Harry all belong to the rare R30b mtDNA haplogroup. This haplogroup might or might not be associated with India. Was it worth it? What do you think?

See also
- Genetic astrology: a tale of misleading claims and legal threats

Related blog posts
- BritainsDNA, the BBC and Eddie Izzard
- Alistair Moffat, BritainsDNA and the BBC - a "uniquely British farce"
- More pseudoscience from Alistair Moffat
- The British: A genetic muddle by Alistair Moffat

References
1. Articles on The Times website are available to subscribers only. The four articles on Prince William’s DNA that appeared in The Times on 14 June 2013 are:
* David Brown. Revealed the Indian Ancestry of William, p1.
* David Brown. Doomed Indian love story had happy end for the daughter who sailed to a better life, p4.
* David Brown. How a retired writer found out that he was within spitting distance of royalty, p5
* Editorial. Accidents of birth: the extraordinary tale of mtDNA haplogroup R30b has lessons for us all, p28
2. Records at Companies House show that Dr James Wilson was appointed as a director of The Moffat Partnership on 12 December 2012.
3. "Revealed the Indian ancestry of William". BritainsDNA press release, 14 June 2013.
4. Zenian D. The Armenians of India. Armenian General Benevolent Union News Magazine, 1 July 2001.
5. Palanichamy M, Sun C, Agrawal S et al. Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia. American Journal of Human Genetics 2004; 75(6): 966–978.
6. Chaubey G, Karmin M, Metspalu E et al. Phylogeography of mtDNA haplogroup R7 in the Indian peninsula. BMC Evolutionary Biology 2008; 8: 227.
7. Harutyunyan A, Khudoyan A, and Yepiskoposyan L. Patrilocality and recent migrations have little impact on shaping patterns of genetic structure of the Armenian population. Genetika (Russian Journal of Genetics) 2009; 45(8):1125-31.
8. Khan R. Prince William may have little to no Indian ancestry. Gene Expression blog, 14 June 2013.
9. Jostins L. How many ancestors share our DNA? Genetic Inference blog, 11 November 2009.
10. Middleton A. Attention The Times: Prince William's DNA is not a toy. The Conversation, 14 June 2013.
11. Hern A. Are there ethical lapses in the Times' story on William's "Indian ancestry"? New Statesman, 14 June 2013.
12. Brice P. Public invasion of genetic privacy for UK royal family? PHG Foundation, 14 June 2013
13. Khan R. Ancestry should not be subject to privacy restraints. Gene Expression blog, 14 June 2013.
14. Johnson B. How a spit of royal DNA makes money for Rupert Murdoch: When science in the news goes terribly, terribly wrong. Stories that Matter, 14 June 2013.
15. Greenslade R. The Times's Prince William splash linked to readers' offer, Greenslade blog, The Guardian, 14 June 2013.

Resources
The ISOGG Wiki has charts comparing the services of all the major genetic genealogy testing companies. The Wiki also includes a list of genetic genealogy mailing lists and forums where people can ask for advice about DNA testing and understanding their DNA results.

Sense About Science have provided a pamphlet entitled Sense About Genetic Ancestry Testing which highlights the limitations of the inferences that can be made from deep ancestry tests.

My commissioned blog post for Sense About Science entitled Sense About Genealogical DNA Testing explains the practical applications of DNA testing for the family historian.

Exploring your Indian ancestry
If you have ancestors who lived in British India I recommend that you join the Families in British India Society. They have an excellent website with a huge selection of genealogical sources which can be found at www.new.fibis.org and they offer many additional services for their members. FIBIS also have their own DNA project which is open to both members and non-members. Further details can be found at www.new.fibis.org/dna.

© 2013-2015 Debbie Kennett

Mitochondrial DNA testing at a new low price

Family Tree DNA have announced a new permanent low price of US $49 (about £32) for their entry-level mitochondrial DNA test. The new low pricing has been made possible thanks to a change to next generation sequencing technology, and brings the starter price for mtDNA testing in line with the new low-cost 12-marker Y-DNA that was introduced on 1st April this year. The $49 price applies to the mtDNAPlus test (HVR1 + HVR2). The basic HVR1 test, which used to be the cheapest available mtDNA test, has now been discontinued. FTDNA have also announced a temporary reduction in the price of their full sequence test which is currently on offer for just $199 or £130 (reduced from $299 or £194). Family Finder, FTDNA's autosomal DNA test, has also temporarily been reduced in price from $289 (£187) to $199 (£130). In an e-mail to group administrators FTDNA have cautioned that the "prices may go up on different tests at any time based on lab volume". Let's hope that the new low prices will attract sufficient sales to make such an increase unnecessary.

A mitochondrial DNA test will tell you about your direct maternal line (ie, your mother, your mother's mother, your mother's mother's mother, and so on back in time). The path of mtDNA transmission can be seen in this diagram on the ISOGG website. An mtDNA test can be used to find genealogical matches on the direct maternal line but also gives you a haplogroup assignment which tells you about your deep ancestry. Haplogroups are the branches of the human mtDNA tree, and the haplogroups all tend to have different geographical distribution patterns. Information on the distribution of the major European mtDNA haplogroups can be found on the Eupedia website.

The choice of mtDNA test will depend on your testing objectives. The mtDNAPlus test sequences the two hypervariable regions - HVR1 and HVR2 - where mutations are more likely to occur. There are 1,143 base pairs in the hypervariable region comprising around 6% of the mtDNA genome. The full mitochondrial sequence (FMS) test sequences all 16,569 base pairs in the mtDNA genome - HVR1, HVR2, plus the coding region where all the genes are found. With both tests your results go into FTDNA's large genealogical matching database and you will be notified of any matches at the three different levels - HVR1, HVR1+HVR2, and HVR1, HVR2 plus the coding region.

The number of matches that you can expect to have varies considerably. Some people like me have no HVR1 matches at all. At the other extreme some people, particularly in haplogroup H, the most common European haplogroup, can have over 12,000 matches at HVR1 and over 2,500 matches at the HVR1+HVR2 level. The full sequence test has only been available at an affordable price for the last few years and consequently there are currently fewer people in the database who have tested at this level. However, the matching criteria are more relaxed at the full sequence level so it is possible to have FMS matches despite having no matches at the lower resolutions. I have no HVR1 or HVR2 matches but I have two full sequence matches. Family Tree DNA have the world's largest collection of mtDNA sequences both at low resolution (HVR1 and HVR2) and at the full sequence level.¹   As of today's date FTDNA have 159,015 mtDNA records in their database, of which 24,579 are FMS tests. With the price reductions we can expect the database to grow at a rapid pace.

The full sequence test is needed for matches in a genealogical timeframe. FTDNA estimate that 90% of exact full sequence matches will fall within 16 generations (around 400 years).²  However, lower resolution matches can sometimes provide clues for further genealogical research if your matches have ancestors from the same geographical area. If you start with the mtDNAPlus test you can always upgrade to the full sequence test at a later date.

For deep ancestry purposes the mtDNAPlus test will give you a base haplogroup assignment (eg, haplogroup H, haplogroup I, haplogroup U4, haplogroup U5, etc). The full sequence test will give you a more detailed haplogroup assignment with lots of extra letters and numbers after the base haplogroup. For example, I am a U4c1a and my dad is a U5a2b3. The most up-to-date version of the mtDNA tree is maintained by Phylotree. You can expect to see your haplogroup updated as new branches are discovered on the mtDNA tree.  If you take the full sequence test you can also contribute your results to scientific research, and you might find that your results help to define a new branch on the tree. My own full sequence results were used in the 2012 paper by Dr Doron Behar et al which provided a major update to the mtDNA tree and introduced the concept of the Reconstructed Sapiens Reference Sequence.³

For assistance with understanding mtDNA results it's a good idea to join the relevant mtDNA haplogroup project at FTDNA. In some cases the project administrators will be able to provide you with a more detailed haplogroup assignment than that provided by FTDNA. It should be remembered that all the administrators are volunteers and some have more time than others to devote to their projects. A full list of mtDNA haplogroup projects can be found in the ISOGG Wiki.

It is astonishing to see how the cost of mtDNA testing has plummeted in the last few years. Family Tree DNA introduced the full mitochondrial sequence test (formerly known as the full genomic sequence test) in 2005 and the test was initially sold for $895 (£580). By 2009 the price had dropped to $439 (£284). Now it is possible to buy the full sequence test for roughly the same price that I paid to purchase the mtDNAPlus test in a sale back in December 2007.

FTDNA are of course not the only company offering mtDNA tests but they are now the clear market leader and offer by far the most competitive prices as well as having the advantage of the largest and most international mtDNA database. While it would be nice to support the British DNA testing companies unfortunately their prices are prohibitively expensive. Oxford Ancestors now charge £199 ($306) for a very basic HVR1 test with no facility to upgrade. BritainsDNA (which also trades as ScotlandsDNA, IrelandsDNA, and YorkshiresDNA) offer a chip-based testing service which looks at around 300 mtDNA markers from across the mtDNA genome. For a female this test costs £170 ($261). This is sufficient to give you a haplogroup assignment but the results cannot be used to check for matches and the test therefore has no genealogical utility.The BritainsDNA test is slightly better value for males as an mtDNA analysis can be purchased for £30 (446) on top of the Y-SNP test which costs £170 ($261) and analyses around 400 Y-SNPs for deep ancestry purposes.  [*Update 18 June 2013: BritainsDNA introduced a new Chromo 2 test on 14 June. The mtDNA Chromo 2 test looks at around 3000 mt SNPs and costs £189 ($299). A new Y-DNA test is also available looking at over 15,000 Y-SNPs.]  However, if you are interested in your deep ancestry the new Geno 2.0 test from the Genographic Project is a much better investment as it tests over 12,000 Y-SNPs along with over 3000 mtDNA markers at a much lower price than the BritainsDNA test. The Geno 2.0 chip also includes autosomal and X-chromosome SNPs. Geno 2.0 Y-DNA and mtDNA results can be transferred to FTDNA free of charge, where you can join the relevant haplogroup, surname and geographical projects. The 23andMe test is a good alternative to the Geno 2.0 test at a reasonable price if you just wish to know your mtDNA haplogroup, and your Y-DNA haplogroup if you are a male. The 23andMe test has the benefit of providing additional health and ancestry information. Both the Geno 2.0 test and the 23andMe test will give you reasonably detailed haplogroup assignments. Note, however, that, like the BritainsDNA test, neither the Geno 2.0 test nor the 23andMe test can be used for genealogical matching purposes on the maternal or paternal lines. For further information on the tests offered by the major genetic genealogy companies see the comparison charts in the ISOGG Wiki:

- ISOGG mtDNA testing comparison chart
- ISOGG autosomal DNA testing comparison chart.
- ISOGG Y-DNA testing comparison chart

It is certainly an exciting time to be involved in the world of DNA testing. The new low introductory prices mean that price is no longer a barrier. No doubt many new people will be added to the FTDNA database who hadn't previously considered testing. If you've not yet had your DNA tested then there is now no excuse for delaying! I will of course be delighted to welcome new members to my Devon DNA Project and my Cruse/Cruise/Crews/Cruwys DNA Project. I'm also hoping that one day someone will take an mtDNA test and will be an exact match for my rare U4c1a haplotype.

References
1. Congiu A, Anagnostou P, Milia N et al. Online databases for mtDNA and Y chromosome polymorphisms in human populations. Journal of Anthropological Sciences 2012 90; 1-15.
2. How do I tell how closely I am related to a mitochondrial DNA (mtDNA) match?  FTDNA FAQ ID 2140.
3. Behar DM, Van Oven M, Rosset S et al. A “Copernican” reassessment of the human mitochondrial DNA tree from its root. American Journal of Human Genetics, Volume 90, Issue 4, 6 April 2012, Pages 675-684.

The following is the official press release from Family Tree DNA:

Family Tree DNA Offers mtDNA Test For $49
Groundbreaking low pricing made possible by cutting-edge Next Generation Sequencing technology that is dramatically driving down costs

HOUSTON, May 9, 2013 /PRNewswire/ -- FamilyTreeDNA.com, the genetic genealogy arm of Gene By Gene, Ltd., has lowered the price of its mid-level maternal line mtDNA test to $49, effective immediately.  The company announced it will offer its mtDNAPlus product at a two-third price reduction permanently, in just its latest step toward universal access by individuals to their personal genetic data. 

"This groundbreaking pricing illustrates how next generation sequencing (NGS) is changing the DNA testing landscape," Gene By Gene President Bennett Greenspan said.  "For Family Tree DNA to be able to offer this test at such an affordable price would have been unheard of before NGS.  We're hopeful that by lowering the price of products like our mtDNAPlus, we'll be able to expand the horizon of DNA testing and, importantly, grow our database to fuel future genetic discoveries."

Earlier this year, Family Tree DNA -- the world's largest processor of Y-DNA and full mitochondrial sequences -- dropped the price of its basic Y-DNA test for males by 60 percent, in order to eliminate cost as a barrier to individuals interested in learning more about their personal genetic and genomic data. 

Since then, the company has been working to do the same with its mtDNA test, which is applicable to both males and females and provides data on the direct maternal line by testing the mitochondria.  The mtDNAPlus product tests Hypervariable Regions 1 and 2, or HVR1 and HVR2, providing individuals with both anthropological and genealogical information. 

With the largest DNA database in the world, Family Tree DNA has processed over 5 million discrete tests for more than 700,000 individuals and organizations since it introduced its Y-DNA test in 2000.  Data gathered from the mtDNAPlus test will be stored, free of charge, in the company's database. If customers are interested in performing any other DNA tests that the company offers in the future, they won't be required to resubmit DNA samples.

Customer Inquiries Individuals interested in Family Tree DNA's $49 mtDNA test, or any of its ancestral testing products, can visit www.familytreedna.com or call (713) 868-1438 for more information.

About Gene By Gene, Ltd. Founded in 2000, Gene By Gene, Ltd. provides reliable DNA testing to a wide range of consumer and institutional customers through its four divisions focusing on ancestry, health, research and paternity.  Gene By Gene provides DNA tests through its Family Tree DNA division, which pioneered the concept of direct-to-consumer testing in the field of genetic genealogy more than a decade ago.  Gene by Gene is CLIA registered and through its clinical-health division DNA Traits offers regulated diagnostic tests.  DNA DTC is the Research Use Only (RUO) division serving both direct-to-consumer and institutional clients worldwide.  Gene By Gene offers AABB certified relationship tests through its paternity testing division, DNA Findings. The privately held company is headquartered in Houston, which is also home to its state-of-the-art Genomics Research Center. 

Media Contact:
Kate Croft
for Gene By Gene, Ltd.
Casteel Schoenborn
888-609-8351
croft@csirfirm.com

Richard III - a king is found

I have been fascinated by the story of Richard III ever since reading the intriguing historical detective story The Daughter of Time by Josephine Tey many years ago. I was therefore glued to the computer this morning watching the BBC's livestream of the Richard III press conference when the results were announced of the five-month investigation into the findings from the archaeological dig in the now world-famous car park in Leicester. The research has been an extraordinary multidisciplinary effort involving the work of experts in archaeology, history, genetics, osteoarchaeology and engineering. The lead archaeologist Richard Buckley announced to cheers from the world's press that "It is the academic conclusion of the University of Leicester that beyond reasonable doubt the individual exhumed at Greyfriars in September 2012 is indeed Richard the III, the last Plantagenet king of England." The full story can be read in an article on the BBC website entitled Richard III dig: DNA confirms bones are king's.

The University of Leicester has today launched a new Richard III website with further information on the research. There is currently an incomplete page of multimedia resources but it looks as though there will be some very interesting videos added to this page in the days and weeks to come, and we can probably expect to see a video of the full press conference for those who missed it.

Genealogy research was crucial to the investigation. The researchers were able to trace two direct matriline descendants of Anne of York, Richard III's sister, both of whom provided DNA samples for mitochondrial DNA testing.  One of the descendants chose to remain anonymous. The second descendant is a Canadian by the name of Michael Ibsen who is now living in London. The genealogical research was greatly facilitated by earlier research by the historian John Ashdown-Hill, and the line that he established has now been independently verified. An outline of the matriline can be seen here. Professor Kevin Schürer, the University of Leicester's Pro-Vice-Chancellor for Research and Enterprise, discusses the process in this YouTube video:

The full details of the DNA testing have not yet been revealed, so we do not yet have confirmation of the haplogroup and we do not know how much of Richard III's mtDNA could be sequenced. However, Michael Ibsen's mother, the late Joy Ibsen, had her mtDNA tested several years ago and we know that she belongs to haplogroup J, one of the rarer mtDNA haplogroups. Assuming that these earlier results were accurate we can, therefore, infer that Richard III is also haplogroup J. The University of Leicester website includes a stunning electropherogram showing the matching mitochondrial DNA results of Richard III, Michael Ibsen and the anonymous donor. There is already a large haplogroup J project at Family Tree DNA and, once the DNA results are known, it will be interesting to see if anyone in the project matches the Richard III DNA signature. Ideally for genealogical matching purposes we require a sequence of the full mitochondrial genome (all 16,569 base pairs). However, because of the rarity of haplogroup J and all the overwhelming evidence from other sources, a partial match would be sufficient in this particular case. Michael Ibsen and his sister do not have any children and their mtDNA line will, therefore, become extinct upon their death, demonstrating once again how important it is to obtain DNA records while you still have the chance.

The researchers are also hoping to extract some Y-chromosome DNA but this research is still in the early stages, and it will probably be some time before we know if this is possible.

Channel 4 has been following the dig and the subsequent research for the last five months and a programme will be shown tonight at 9.00 pm (UK) called Richard III: King in the Car Park. A preview can be seen here:

I wonder if the exciting discovery of the remains of Richard III will now open the doors for a scientific investigation of the remains of the two skeletons discovered under the stairs in the Tower of London in 1674 which are thought to be the bodies of the Princes in the Tower. The bones were reburied in Westminster Abbey but the Queen and the church authorities have refused previous requests to exhume the bodies.

Update
See this thread on the Genealogy DNA mailing list and a further follow-up thread for a discussion of the mtDNA results.

Update 6 February 2013
The Richard III press conference can now be seen on YouTube.

Update 8th February 2013
James Lick has used his mtDNA haplogroup prediction program to analyse what is known of Richard III's mtDNA sequence. See his blog post "Analyzing the mtDNA of the presumed Richard III skeleton with mthap" and the follow-up blog post in which he suggests that the inferred haplogroup is most likely J1c2c. The J1c2c haplogroup has been confirmed by Dr Turi King in an article published in Science News.

Update December 2014
The scientific paper with the results of the DNA analysis has now been published. See my blog post Richard III and the use of DNA as evidence for further details.

Useful links
The following links might also be of interest:
- Leicester University's Richard III website
- Richard III: The King in the Car Park (Channel 4 website)
- Press release from the University of Leicester
- Press release from the Richard III Society
- The University of Leicester's Richard III Facebook page
- The Richard III Society
- The University of Leicester's Greyfriars Project website
- Live updates from the This is Leicestershire website
- Facial reconstruction shows how king may have looked
- Richard III: The twisted bones that reveal a king
- BBC 4 Today interview with the historian John Ashdown-Hill
- The Last Days of Richard III and the Fate of his DNA: the Book that Inspired the Dig by John Ashdown-Hill
- Wikipedia article on the exhumation of Richard III
- Now is the winter of our uncertainty made glorious summer by this sun of journalistic zeal by Julian Champkin

© 2013 Debbie Kennett

Major revision of the mtDNA tree

An important new paper has today been published in the American Journal of Human Genetics which proposes a major revision to the mitochondrial DNA tree. The abstract says:

Mutational events along the human mtDNA phylogeny are traditionally identified relative to the revised Cambridge Reference Sequence, a contemporary European sequence published in 1981. This historical choice is a continuous source of inconsistencies, misinterpretations, and errors in medical, forensic, and population genetic studies. Here, after having refined the human mtDNA phylogeny to an unprecedented level by adding information from 8,216 modern mitogenomes, we propose switching the reference to a Reconstructed Sapiens Reference Sequence, which was identified by considering all available mitogenomes from Homo neanderthalensis. This ''Copernican'' reassessment of the human mtDNA tree from its deepest root should resolve previous problems and will have a substantial practical and educational influence on the scientific and public perception of human evolution by clarifying the core principles of common ancestry for extant descendants.

The full paper can be read here.

Many of the sequences that were used in this paper to refine the mtDNA tree were submitted by customers of Family Tree DNA (including me!) who had taken the full mitochondrial sequence test and made their results available for research purposes. Rebekah Canada and Bill Hurst, the volunteer administrators of the haplogroup H and K projects helped with the H and K results. The authors publicly acknowledge the contribution of the genetic genealogy community in their acknowledgements: "We thank the genealogical community for donating their privately obtained complete mtDNA sequences for scientific studies and FamilyTreeDNA for compiling the data. We thank FamilyTreeDNA for supporting the establishment of the herein released website. We thank Eileen Krauss-Murphy of FamilyTreeDNA for help with assembly of the database. We thank Rebekah Canada and William R. Hurst for help with the assembly of haplogroup H and K samples, respectively."

A new mtDNA community website has been launched to accompany the paper. Anyone with full mitochondrial sequence results can upload their results to this website and get an up-to-date haplogroup assignment.

The mtDNA tree can also by seen at Phylotree which has just released Build 14 to account for the big change. Mannis Van Oven, who maintains the Phylotree website, is one of the authors of the new paper. The 4,265 mtDNA full sequence results used for this new paper, including a substantial proportion from FTDNA customers, are being added to the GenBank research database. There are already 1,237 FTDNA customer-submitted results on GenBank. Private submissions from FTDNA customers will now constitute almost half of the mtDNA sequences on GenBank.

©2012 Debbie Kennett

Indian mitochondrial DNA haplogroups

Last Saturday I was honoured to be invited to give a lecture on DNA testing at the Families in British India Society's Annual General Meeting. FIBIS members are particularly interested in mitochondrial DNA testing as the British men who lived in India often married local women. In many cases the only record of Indian ancestry will be found through a DNA test. FIBIS has just launched a new DNA project for its members at Family Tree DNA, and it will be very interesting to see what discoveries they make.

When preparing the presentation I was unable to find any reliable information on the distribution of mitochondrial DNA haplogroups in India. Family Tree DNA has the world's largest mtDNA database, and Eileen Krause very kindly searched the FTDNA database for me to compile statistics on the distribution of mtDNA haplogroups of known Indian origin. She has kindly given permission for me to reproduce the figures here. As Family Tree DNA is a commercial testing company it should be noted that their database is not necessarily representative, but these figures nevertheless give a good idea of the range of mtDNA haplogroups that are likely to be found in anyone of Indian ancestry.

Haplogroup	Percentage
M	51%
U	19%
R	12%
H	5%
HV	3%
W	3%
N	2%
C, F, K, J, T, A, D, L2, B, I, L0, L1, X	<1%

© Debbie Kennett 2011

Haplogroup U4 project

I wrote back on 7th June 2008 about my mitochondrial DNA (mtDNA) test and my rare U4 haplogroup. At that time I joined the mtDNA haplogroup U4 project at Family Tree DNA, but the project was very quiet and I received no communications from the group administrator. It therefore came as no surprise when the admin announced at the end of August that he was stepping down. William Allen, who runs the new U4 blog, has taken over as the group admin, and I offered to help out as a co-administrator. We are joined by Ron Scott, who is an expert on mtDNA and has done a considerable amount of work on the phylogeny (the family tree) of haplogroup U4 and all its subclades. Inevitably the project took up far more time than I originally envisaged, and I have been somewhat preoccupied in recent weeks, hence the lack of postings to this blog. I spent a lot of time updating the U4 project website, and have been busy recruiting new participants from Mitosearch, the public mtDNA database. My efforts were rewarded by a considerable boost in membership from 160 participants when we took over the project on 25th August to 280 as of today's date. The project is continuing to grow at a steady rate. If you have had your mtDNA tested either by Family Tree DNA or the Genographic Project and you belong to haplogroup U4 then I do hope you will join our project. It is free to join, and no further tests are required.

Mitochondrial DNA has always been somewhat neglected by family history researchers, largely because fewer mutations occur and, with the standard HVR1 and HVR2 mtDNA tests, people can often have large numbers of matches, the majority of which will be of no genealogical significance. In 2005 Family Tree DNA introduced a full-genomic sequence (FGS) test, which can refine matches in a genealogical time frame, but the test has always been very expensive, and beyond the reach of the average researcher. However, earlier this month Family Tree DNA announced a special promotion for their existing customers with the offer of a substantial reduction in the cost of the FGS test.

Dear Family Tree DNA customer

I am pleased to make a very special announcement about our Full Mitochondria Sequence test.

As you know, this test has continually dropped in price from its initial introduction at $895 in 2005. These price decreases were related to volume and workflow, translating productivity into economies of scale that allowed us to reduce prices to those customers interested in testing their full mitochondrial sequence.

Now Family Tree DNA is doing it again, but this time we are going to take advantage of new technology that will allow us to run more samples in less time, and the savings are substantial. We expect that this price decrease will hearken a new era of Full Mitochondria Testing for the entire Genealogical community!

We will jumpstart this new era of complete mtDNA testing with an aggressive price in order to build the comparative database to the levels genetic genealogists require to answer precise ancestral and geographic questions.

So now on to the news that you've been waiting for. A new price for the mtFull Sequence test will be introduced in November but until then we are offering our current customers a promotional price through October 31st, 2009...

Depending upon the time that it takes to process these upgrade orders using our new hardware, we may experience a back order or lag time in November. If this occurs we expect to resolve the backlog in December.

The promotional prices for existing Family Tree DNA customers are:

- US $229 (was $439) for first time mtDNA test takers
- US $179 for those who have already tested HVR1 and HVR2
- US $199 for those who have already tested HVR1

The new price from November has not yet been announced but will no doubt represent a considerable saving on the current project price of $439, and will finally make the FGS test an affordable option for anyone wishing to use modern DNA techniques to aid research into their direct maternal line. Family Tree DNA are currently the only company to offer the full-sequence test. No doubt other companies will follow in due course, and the FGS test will eventually become the standard test for matriline researchers. It will however take time for the database to reach critical mass. Nevertheless, despite the fact that the test was previously so expensive, Family Tree DNA already have a considerable advantage over their competitors with 6,180 full-sequence tests in their database. We have had a large number of upgrade orders in the U4 project, and I have also ordered the upgrade for myself. No doubt other projects will have seen similar sales volumes. It can only be a matter of time before the FGS database grows to a sufficient size to answer some of our genealogical questions.

My mtDNA results

I've now received my mitochondrial DNA (mtDNA) test results from Family Tree DNA. Somewhat surprisingly my maternal line belongs to haplogroup U4, a small Indo-European haplogroup which seems to be quite rare. The haplogroup is found in only 1.63% of the population of England and Wales. The highest frequencies of U4 are found in southern Siberia, and it is also found in Eastern Europe, the Urals, in some German-speaking populations and in a few lineages in India.

Brian Sykes gives names to the seven main European mitochondrial haplogroups in his book The Seven Daughters of Eve. All the women in Europe can supposedly trace their genetic ancestry back to one of these seven women. Haplogroup U4 is not one of Sykes's original clan mothers but is a sub-clade or sub-branch of haplogroup U, otherwise known as Ursula. "Ursula" lived around 45,000 years ago. "Ulrike" is of more recent origin and lived around 18,000 years ago. Sykes describes Ulrike thus: thus:

The clan of Ulrike (German for Mistress of All) is not among the original "Seven Daughters of Eve" clans, but with just under 2% of Europeans among its members, it has a claim to being included among the numerically important clans. Ulrike lived about 18,000 years ago in the cold refuges of the Ukraine at the northern limits of human habitation. Though Ulrike's descendants are nowhere common, the clan is found today mainly in the east and north of Europe with particularly high concentrations in Scandinavia and the Baltic states.

I have so far been able to trace my direct maternal line back to Mary Ann Butler, the daughter of James Butler, a labourer. Mary Ann was born in Purton, Wiltshire, in around 1815. She married Moses Ball in 1842 in Walcot, Somerset. Moses and Mary Ann had six children who were born in Sherston, Wiltshire, and Westonbirt, Gloucestershire. My maternal line continues with their daughter Hannah Ball, who moved to London and married William Saunders, a coachman and stage coach driver, on 16th June 1872 at the Parish Church of St Marks in North Audley Street. The other names in the later generations of my maternal line are Tidbury, Rattey and of course Cruwys.

Mutations occur much less frequently in mitochondrial DNA and the tests are therefore not so useful as the Y-DNA test which we are using for the Cruwys DNA Project. Most people who take the mtDNA test have large numbers of matches in the various databases. Not surprisingly, with my rare U4 haplotype, I do not have a single match in the Family Tree DNA database. I have also uploaded my results to Mitosearch, the public mtDNA database sponsored by Family Tree DNA, but again I do not have any matches. It is also possible to search the Mitosearch database by haplogroup. There are only 472 people in the whole world with my haplogroup in the database at present.

I regard the mtDNA test as an investment for the future. My grandmother was an only child and my great-grandmother was the only daughter in her family. My sister and I have both had sons so our direct maternal line is now at an end. Sons do of course inherit mtDNA from their mother but they cannot pass it on to the next generation. My mtDNA results will have more value as more people in the UK get tested and once I start to make further progress with my research into my maternal line in Wiltshire. With a rare haplogroup it should also be much easier to verify my maternal line.