Friday, 20 December 2013

A first look at the BritainsDNA Chromo 2 Y-DNA and mtDNA tests

Larry Vick has kindly shared screenshots of the results from his Chromo 2 test from BritainsDNA*. I wrote in my previous blog post about the results from his All My Ancestry admixture test. We will now have a look at his Y-DNA and mtDNA test results. The Chromo 2 test is a useful product for anyone wishing to have a detailed Y-DNA haplogroup assignment but who doesn't wish to pay out for one of the new but much more expensive comprehensive Y-chromosome sequencing tests. The test looks at around 15,000 Y-SNPs. For anyone with ancestry from the British Isles the Chromo 2 Y-DNA test is currently probably a better choice than the Geno 2.0 test from the Genographic Project. However, this is a rapidly changing market, and there are indications that the Genographic Project will be offering a new chip in 2014. For up-to-date comparisons of the various Y-SNP tests on the market see the Y-DNA SNP testing chart in the ISOGG Wiki.

There are a number of different options for the Chromo 2 test. The Chromo 2 Y-DNA test costs £189 ($299). A cheaper option is to purchase the Raw Y-DNA test for £129 ($199) which gives you your raw Y-DNA results without the ancestral and interpretative reports. If you are ordering the Raw Y test you will need to ensure that you share your results with the relevant haplogroup project administrators so that they can determine where your SNPs are placed on the Y-SNP tree as the position of many of the SNPs on the Chromo 2 chip is not yet known. The Chromo 2 test can also be purchased in packages in combination with the All My Ancestry test and a mitochondrial DNA haplogroup test. Larry had previously tested with Ethnoancestry (the former name of BritainsDNA) and was able to upgrade to the new test at a discounted price so he opted to have the full works. Make sure you click on all the images below to enlarge them to see the full details of each report.

The following screenshot shows the Y-DNA results welcome screen. Larry is haplogroup Q and BritainsDNA have identified his most downstream SNP as S324 (also known as L56). Larry tells me that he got a much better haplogroup assignment from BritainsDNA than he did from the Geno 2.0 test, and Chromo 2 has confirmed everything he already knew about his haplogroup except for what he has now discovered from the Full Genomes comprehensive sequencing test.

The Genetic Signature Report lists all the SNPs on the Chromo 2 chip for which Larry tested positive. Not all of these SNPs have been placed on the Y-tree and it is possible that his subclade assignment will be updated in future as the structure of the tree becomes clearer.

The Haplogroup Story provides a somewhat fanciful narrative about the origins of haplogroup Q which is defined by the SNP M242. It is of course mere speculation that haplogroup Q originated in the Altai mountains in Central Asia as they suggest. BritainsDNA give nicknames to the base haplogroups, and Altai is the name they have chosen in this case to represent haplogroup Q. Note that these nicknames have no scientific basis and should not be taken literally.

The World Distribution Map shows the percentage distribution of haplogroup Q in various populations around the world. BritainsDNA tell us that "the results for the world distribution have been brought to you from a combination of the published literature, our own data, and databases available from other research projects". It would have been helpful to have the full details of the sources used but unfortunately this information has not been provided. You can zoom in and out of the map to see the distribution of your haplogroup in different countries.

The Regional Distribution Map provides a breakdown of the distribution of haplogroup Q in the British Isles. The map represents "the locations of lineages 100 years ago" and is seemingly based on information provided by BritainsDNA customers who have been asked to give the birth place of their paternal grandfather.
This is an interesting feature which is not provided by any other companies. However, it would have been useful to have more details of the sampling process and, more specifically, the number of people sampled in each country. The date when the map was generated is not given and there is no indication as to how often the company plan to update the map.

The Four Nations map shows the distribution of Larry's haplogroup in the four countries that make up the British Isles. The company tell us: "The ancestral data that you and all of our customers provided on ordering has informed both the regional distribution across Britain and Ireland and uncovered the frequencies across our four home nations." The grandparents' place of birth is used for this chart which is again intended to represent "the location of lineages 100 years ago or more". As with the maps, this chart would have been more meaningful if details of the number of samples in each country had been provided. Presumably such information is considered to be commercially sensitive.

The Phylogenetic Tree shows the position of Larry's haplogroup in relation to the full Y-SNP tree. There is a slider to zoom around the tree, and a red line allows Larry to trace his lineage back to the root of the tree. With the anticipated SNP tsunami in 2014 the Y-tree is likely to undergo major restructuring, and this tree is likely to become out of date very quickly. ISOGG maintains the most up-to-date version of the Y-SNP tree.

The Y-DNA haplogroup frequencies chart shows the percentage of BritainsDNA customers who belong to each haplogroup.  Again, the underlying data are not provided, and it is not clear whether these frequencies include the whole customer base or just those customers who have a paternal grandfather who was born in the British Isles. The haplogroups are identified by their name and also by their BritainsDNA nickname. Note that the ISOGG Wiki has a chart which lists all these nicknames and the alternative SNP names.

BritainsDNA also offer the option to download the raw Y-SNP data. Larry sent me his raw data file which is in the form of a Notepad file with a list of all the SNPs tested. The results show whether Larry was positive or negative for each SNP tested and the genotype (the A, C, T and G letters) for each SNP. The file is provided in tab-delimited text file which can be opened up in a spreadsheet program.

Larry's mtDNA results follow the same format. Here is a screenshot of his mtDNA results welcome page.

Larry has been assigned to haplogroup H212b4, which is the same assignment he received for his full mitochondrial sequence test from Family Tree DNA. The Chromo 2 test covers around 3000 mt SNPs, and provides the same coverage as the Geno 2.0 chip. There are 16,569 base pairs in the full mitochondrial genome. 3000 SNPs is usually sufficient to give a reasonably detailed haplogroup assignment, but interpretation errors can occur and it is then necessary to have access to the raw data. There is, however, no option to download the raw mtDNA data. Larry tells me that BritainsDNA have advised him that they will not be providing the raw mtDNA data or indeed the raw autosomal DNA data. I would suggest that anyone who has taken an mtDNA or autosomal test with BritainsDNA should write to the company and ask for their raw data, and perhaps they will eventually change their mind. For a comparison of the mtDNA tests available see the ISOGG mtDNA testing comparison chart.

All in all I think the Chromo 2 test is a useful product for males wishing to have a detailed Y-DNA haplogroup assignment. It is certainly a big improvement on the previous offering from BritainsDNA/ScotlandsDNA which tested only 300 Y-DNA SNPs and 300 mtDNA SNPs, and was accompanied by a generic, melodramatic and fanciful narrative story with tales of the eruption of Mount Toba and ridiculous statements such as the supposed "fact" that "what directly caused populations to expand rapidly was the invention of porridge". The new haplogroup frequency charts and maps provide much more useful information, though the reports would have been more informative if details of the sample sizes had been provided. The experienced genetic genealogist is probably best advised to stick with the Raw Y test, unless he has a particular desire to have the charts and maps. If you've already taken a standard Y-STR test it is always best to seek advice first from the haplogroup project administrators or the relevant haplogroup-specific mailing list. In some cases it's possible to predict the most downstream Y-SNP with high confidence from a Y-STR signature and it is then only necessary to order a single SNP for $39 to confirm your placement on the Y-tree. It is also worth keeping up with the various genetic genealogy mailing lists and Facebook groups because there are likely to be many exciting new developments in 2014.

*Note that BritainsDNA also trades as ScotlandsDNA, IrelandsDNA, YorkshiresDNA and CymruDNAWales.

Related blog posts
- A first look at the Chromo 2 All My Ancestry test from BritainsDNA
Alistair Moffat, BritainsDNA and the BBC - a "uniquely British farce"
- More pseudoscience from Alistair Moffat on the BBC
BritainsDNA, the BBC and Eddie Izzard
The British: a genetic muddle by Alistair Moffat
BritainsDNA, The Times and Prince William: the perils of publication by press release
The saga continues - CymruDNAWales, S4C, the Tudor surname and "Who are the Welsh?"
More on the S4C DNACymru controversy and my review of "Who are the Welsh?"

© 2013 Debbie Kennett

A first look at the Chromo 2 All My Ancestry test from BritainsDNA

Larry Vick has very kindly shared some screenshots with me from his BritainsDNA* Chromo 2 test. Larry previously tested with the company in the days when it was known as Ethnoancestry. As an existing customer he was given the opportunity to order the Chromo 2 test at a very favourable price. Larry ordered the combination package which includes a Y-DNA (fatherline) test, an mtDNA (motherline) test and the All My Ancestry (biogeographical analysis) test. I will cover the All My Ancestry test in this post and will discuss the other tests in a follow-up post. Click on the images to enlarge them.

The All My Ancestry test analyses around 250,000 autosomal SNPs. The screenshot below shows the All My Ancestry welcome screen.  There are three different viewing options: Global Connections, Population Percentage, and Chromosome Painting.

The Global Connections menu compares your results with reference samples from around four thousand people from around the world. The results are plotted on a colour-coded chart and you can see which population is your closest match. There is a drop-down list which gives you the option to choose a variety of alternative views: Worldwide 1; Worldwide 2; African; Sub-Saharan; West Asian; South and Central Asian; East and Northern Asian; Hispanic and Afro-Caribbean 1; Hispanic and Afro-Caribbean 2; Native American mixture; and Jewish mixture. The image below shows the Worldwide 1 view.

This image shows the European view from the Global Connections menu:

The next menu allows you to look at your Population Percentages. This plot "uses a population genetic model to estimate your overall ancestry and puts this in context using nearly 4000 people from across the world". There is again a drop-down list which allows you to see your results compared to a number of different populations. The following options are available: global; Africa; Europe; West Asia; South and Central Asia; East and North Asia; and Hispanic-Afro-Caribbean-Native American. The following screenshot shows the global comparison:

This screenshot shows the European comparison:

The final viewing option is the Chromosome Painting. This allows you to see the contribution made to each of your chromosomes from three broad population groups: West Eurasian, Sub Saharan African and Asian-Native American. The company say "An ancestor six or more generations ago will have only contributed a small segment of DNA to your genome but this method can see these small segments which are not obvious in methods which provide a summary of the whole genome." As can be seen from the painting below this method has detected what are possibly small segments of African and Native American DNA.

Larry describes his documented ancestry as follows.
I think my ancestry would be best described as colonial American with a lot of UK, significant Irish, some German, and a little African and Native American mixture. I am not sure of the amount of African and Native American. My mother's 2nd great grandmother was from an area of tri-racial people, and I have no idea as to who her African or Native American ancestors were (in fact I don't even know my mother's 2nd great grandmother's parents' names). My mother's ancestry paintings have merely supported a family story about her 2nd great grandmother being from Newman's Ridge in Hancock County, Tennessee.  This 2nd great grandmother's maiden name was COLLINS, and that is a very prominent Melungeon surname (the reputed founder of this area was Vardy COLLINS).
I have to say I've personally never been able to work up much enthusiasm for these admixture tests. I already know that all my documented ancestors are from the British Isles and none of the tests are as yet able to tell me anything more than I already know from my genealogical research. However, Larry's genetic ancestry is much more interesting than mine which makes the results a little more appealing. I particularly liked the very colourful population percentage plots, a feature which is not available from any of the other testing companies. It would have been helpful to have information on the reference populations used for the analysis, something which all the other companies now provide. Another feature which is lacking is the ability to download the raw autosomal data. Compared to the alternative offerings on the market the All My Ancestry test is rather expensive at £169 ($269). It is a little cheaper when bought as part of a package in combination with the Chromo 2 Y-DNA and mtDNA tests. For a comparison of the autosomal DNA offerings from the other testing companies see Tim Janzen's autosomal DNA testing comparison chart in the ISOGG Wiki. The BritainsDNA All My Ancestry test is not yet included on this chart but Tim will no doubt wish to update it in due course when he's had the chance to assess his own results.

* Note that BritainsDNA also trades under the names ScotlandsDNA, IrelandsDNA, YorkshiresDNA and CymruDNAWales.

Related blog posts
- A first look at the BritainsDNA Chromo 2 Y-DNA and mtDNA tests
Alistair Moffat, BritainsDNA and the BBC - a "uniquely British farce"
More pseudoscience from Alistair Moffat on the BBC
BritainsDNA, the BBC and Eddie Izzard
The British: a genetic muddle by Alistair Moffat
BritainsDNA, The Times and Prince William: the perils of publication by press release
- The saga continues - CymruDNAWales, S4C, the Tudor surname and "Who are the Welsh?"
- More on the S4C DNACymru controversy and my review of "Who are the Welsh?"

© 2013 Debbie Kennett

Monday, 16 December 2013

The British: a genetic muddle by Alistair Moffat

The British: A Genetic Journey is the latest book by Alistair Moffat, the co-founder of the DNA testing companies BritainsDNA, ScotlandsDNA, IrelandsDNA and YorkshiresDNA. Moffat was previously the Director of the Edinburgh Fringe Festival and Director of Programmes at Scottish Television. He currently also serves as the Rector of St Andrew’s University. Moffat’s business partner is James Wilson, who works at the Centre for Population Health Sciences at the University of Edinburgh, and is BritainsDNA’s chief scientist.

According to the pre-publication publicity from the publisher Birlinn Books the book was originally planned to be written by both Alistair Moffat and James Wilson with the comedian Eddie Izzard lined up to write the foreword. It was originally scheduled for publication in March 2013 to coincide with the screening of the BBC programme Meet the Izzards in which Eddie Izzard, with the aid of Jim Wilson, went on a journey to explore his deep ancestry though DNA testing.

For whatever reasons the book was obviously extensively delayed but it was eventually published at the beginning of November. Until fairly close to the publication date the book was shown on and other websites with both Jim Wilson and Alistair Moffat as co-authors and with the advertised foreword from Eddie Izzard. An example of the old cover can be seen here.

I was therefore somewhat surprised when I received my copy of the book from Amazon to find that Alistair Moffat was listed as the sole author. I could not find Jim Wilson’s name mentioned anywhere in the book. Furthermore, the long-promised foreword from Eddie Izzard is notable by its absence. Eddie Izzard similarly doesn’t get a mention in the book despite the fact that BritainsDNA did the DNA testing for Meet the Izzards and even went to the trouble of setting up a dedicated IzzardsDNA website.

The book is described on the dustjacket as being “based on exciting new research”. Having now read the book I’m at a loss to understand quite what this exciting new research actually is. The book itself mostly focuses on history and pre-history, with a heavy emphasis on pre-history, and there is very little on genetics. The genetics component largely consists of summaries of a small selection of genetics papers combined with a rehash of the many press releases issued by BritainsDNA over the last few years, some of which have attracted publicity in the British media.

Chapter 6 covers the Roman occupation of Britain. Alistair Moffat read out large extracts from this chapter during his lecture at Who Do You Think You Are? Live in February 2013.  I wrote about the misconceptions in this talk at the time. Sadly nothing has changed and no new evidence is offered.

In Chapter 9 on “The Royal British” we are regaled with the story of Prince William’s supposed Indian ancestry. This story was published in an advertorial in The Times newspaper in June this year and I discussed the problems with this research in an earlier blog post. Unfortunately, the book adds no further evidence to support the claims.

The casual reader of the book who is not familiar with the scientific literature will possibly have difficulty distinguishing between the genuine research published in peer-reviewed scientific journals and Alistair Moffat’s own somewhat unique take on our ancestral origins. There is not a single reference in the book and it is therefore not clear which genetics findings are based on peer-reviewed research, which sections are based on BritainsDNA’s unpublished research, and which sections are merely Moffat's own speculations. Some of the more ludicrous interpretations appear to be the product of Moffat’s fertile imagination.

The reader who is not familiar with the basics of genetic genealogy will probably also be somewhat confused by Moffat’s rather muddled terminology and his highly romanticised and at times laughable interpretations of our genetic history. He appears to have a very limited understanding of genetics. Confusingly he uses the word “marker” to describe both haplogroups (the branches of the human Y-chromosome DNA and mitochondrial DNA trees) and the markers known as SNPs – single-nucleotide polymorphisms –  that define those branches. For example, the mtDNA haplogroup L3 is described as being “a marker labelled L3”. This is particularly misleading for mitochondrial DNA because haplogroups are sometimes defined by several SNPs and, as can be seen on Phylotree, there are in fact three markers commonly used to define L3. Furthermore, especially for mtDNA, the same SNPs can occur in parallel in different haplogroups.

Moffat has a touching but misguided faith in the “ability of scientists to identify the origins and dates of DNA markers and to use them to track the movement of people across the Earth”. He tells us that “The dim and very distant prehistoric past can come brilliantly and movingly alive when the passage of a marker is traced from Manchuria and the shores of the Yellow Sea in the North Pacific clear across the Eurasian landmass to be found in Edinburgh in 2013.”  He attempts to correlate specific "markers" (more correctly, haplogroups) with ethnic groups or tribes such as the Vikings, the Picts, and the Maetae based on the flimsiest of evidence, conjuring up pictures in the reader’s mind of little bands of haplogroup armies migrating in unison in order to preserve the integrity of their markers. Unfortunately our genetic ancestry is somewhat more complicated than that. The problems of making such simplified interpretations and assigning arbitrary labels to groups and cultures are nicely summarised in Sense About Genetic Ancestry Testing, a pamphlet published earlier this year by Sense About Science.

Moffat unfortunately makes no attempt to explain any of the marker names and labels that he uses and provides no resources where the reader might seek clarification. The problem is readily apparent in the opening chapter of the book where Moffat’s imagination runs riot with the descriptive names used for the genetic groups that he describes:
     "On any London Monday morning packed trains rattle into King’s Cross, Euston, Cannon Street and Waterloo. The brakes hiss, the doors open and Saracens, Saxons, Berbers, Cave Painters, Vikings, Angles and Picts pour out onto the platforms. On any Saturday afternoon at Ibrox, St James’s Park, Old Trafford and Anfield crowds of Caledonians, Deer Hunters, Kurgans, Iberians, Rhinelanders and Anatolians roar on their teams, passionate in support, their sporting allegiances central to their identities. On any weekday morning all over Britain the school run delivers the children of the First Farmers, the Shell Collectors, the Foragers, the Shebans and the Yenesei to the gates of the playground.
     These are the British, named by their DNA markers, all of them immigrants, all of them descendants of men and women from somewhere else, from the distant, shadowy millennia of deep time, the survivors of many epic journeys lost in the darkness of the past."
The names he uses here are in fact the nicknames that BritainsDNA assigns to the various Y-DNA and mtDNA haplogroups and their sub-branches. There is a page in the ISOGG Wiki which provides a translation of the BritainsDNA nicknames for the Y-DNA haplogroups, but such names have no scientific basis. Furthermore, the ancestry we inherit on the Y-chromosome line (males only) and the mitochondrial DNA line represents only a decreasing fraction of our total ancestry as we look further back in time.

BritainsDNA mostly use their own proprietary S series names for the Y-SNPs that define the male-line branches of the tree, and these marker names are used throughout the book. A full list of the alternative and better known SNP names can be found in the ISOGG Y-SNP index.

In Moffat’s confused and simplified version of our genetic ancestry “Only 1.5% of all British and Irish Y-chromosome markers, principally M26 [the SNP that defines haplogroup I2a1a] from the ice age refuges and S185 [also known as L161.1, the SNP which defines haplogroup I2a1b2] from across Doggerland, certainly predated the arrival of the farmers c4000 BC, and a further 3.5% may have done.” We are then told that “Archaeology and DNA appear to agree on the origins of the vast majority of the incomers to Britain and Ireland after c4200 BC, those enriched for the G lineages.” The reason for this is supposed to be that the Y-chromosome “marker” of Ötzi the Iceman is “in the haplogroup G and it makes a clear link with the development of farming in Europe.” He then adds: “Almost certainly, those who carried the G markers sailed to Britain and Ireland in groups.”

The true story is of course much more complicated than that, and scientists and archaeologists don't have all the answers. There is no general agreement as to when and, most importantly, where the various haplogroups originated. There is also no evidence that any haplogroup was exclusive to any particular ethnic group in the past. Ancient DNA analysis and comprehensive Y-chromosome sequencing will provide further insights. Only a limited number of Y-DNA samples have been extracted from ancient DNA specimens to date. Richard Stevens provides a useful map showing the location of the finds together with details of the associated scientific papers where the results were published. Note that no ancient Y-DNA samples have yet been analysed from the British Isles. Comprehensive Y-chromosome sequencing is still in its infancy though we can expect to see a flood of new results in 2014 from genetic genealogists who have taken the state-of-the-art comprehensive Y-DNA sequencing tests. And of course the Y-chromosome markers, which are the primary focus of Moffat's book, only tell us about our ancestry on the fatherline or patriline, which represents only a small percentage of our total ancestry.

At times the prose is so melodramatic as to be unintentionally hilarious. For example, Moffat correctly notes that R1b-M269 is the most common haplogroup in Europe, and that it increases in frequency from east to west, but then goes on to offer the following explanation for the dominance of R1b (pages 99-100):
     "This increase in frequency from east to west obviously shows the direction of travel and the marker’s origins. R1b-M269 is the DNA of a second wave of farmers and as this revolutionary way of life, of producing food, washed across Europe, this marker, which first arose in the Near East, became tremendously widespread. And its dynamic movement to every corner of the continent shows something unarguable, that this new wave of farming and farmers was not a process of acculturation or adoption. Rather, it was the cultural cargo of an invasion, the deposit of a takeover by new people, the bearers of the marker of R1b-M269.
     Recent research has dated the origin of the cluster of R1b Y-chromosome markers to the middle of the third millennium BC and attached its dramatic spread across Europe to the advance of the Beaker People. And it seems that there was conflict, perhaps even something close to genocide. When the carriers of the R1b lineages arrived in Britain and Ireland, they took over, and this process must have involved the elimination of many of the men who carried the G lineages of the first farmers." 
Y-DNA haplogroup G is indeed the predominant haplogroup found in the very limited range of ancient DNA samples from the Neolithic period and only one R1b sample has been published to date, but we cannot extrapolate from 40 or so samples and conclude that all of the first farmers were haplogroup G. The published scientific papers on R1b are in fact contradictory and do not agree on the date of the origin of R1b. Mass genocide is one far-fetched hypothesis to account for the present-day dominance of R1b in Europe, but it is equally possible that R1b has spread dramatically purely by chance. Moffat is seemingly unaware of the work of his Chief Scientist, Jim Wilson, who was one of the authors of a recent paper entitled The peopling of Europe and the cautionary tale of Y chromosome lineage R-M269 (Busby GBJ, Brisighelli F, Sanchez-Diz P et al. Proceedings of the Royal Society B 2012; 279: 884–892) in which the authors concluded that "the existing data and tools are insufficient to make credible estimates for the age of this haplogroup, and conclusions about the timing of its origin and dispersal should be viewed with a large degree of caution". A recent paper by Sikora et al in Investigative Genetics (2013; 4: 25) entitled Modeling the contrasting Neolithic male lineage expansions in Europe and Africa provides a summary of the contrasting findings in the literature. The authors use a simple demographic model which suggests that "in Europe, the R1b lineage experienced an extremely rapid and extensive increase as soon as it entered the continent, expanding more than a thousandfold in a few generations".

The lack of basic research that has gone into the genetics aspects of the book is evidenced in the statement in the final chapter on Comings and Goings: “Near Eastern markers can be distinguished in the modern population of Britain but specifically Jewish DNA is hard to find.” Moffat goes on to provide an outdated description of the Cohen Modal Haplotype, but seems to be blissfully unaware of the large number of scientific studies investigating “Jewish” DNA. It has been found that there are a number of Y-DNA and mtDNA subclades that are almost exclusively confined to people with Jewish ancestry. This oversight might perhaps explain why, as I wrote in an earlier blog post, his company mistakenly ascribed a Japanese origin to an Ashkenazi Jewish customer.

Some of the genetic findings he discusses may be more plausible, but it is a shame that the company’s scientists have so far failed to publish any of their research. I do not feel qualified to comment on the historical content which comprises the majority of the book. This subject matter might well be of interest to the general reader who wishes to have an overview of British history and pre-history. However, the lack of references is a cause for concern, especially in view of the fact that Moffat has a background in journalism rather than academic research.

However, if you are interested in the genetic history of the British then I regret that this genetic jumble of a book cannot be recommended. I can only think that Jim Wilson and Eddie Izzard are very grateful that they do not have their names associated with it.

Despite my reservations about Alistair Moffat's book, please note that the Chromo 2 test offered by his company BritainsDNA is a credible and useful test for males wishing to explore their deep ancestry and who would like to have a detailed Y-DNA haplogroup assignment. There are also a number of other tests on the market at varying prices. For details see the ISOGG Y-SNP testing chart. For an explanation of the different deep ancestry tests and possible future developments in this fast-changing market see my article on a confusion of SNPs. Y-SNP testing is best co-ordinated through a Y-DNA haplogroup project. Please note that Y-SNP tests do not currently have a direct application for genealogy. For information on suitable tests for genealogical purposes see the beginners' guides to genetic genealogy in the ISOGG Wiki.

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

© 2013 Debbie Kennett

Thursday, 12 December 2013

Recordings of Royal Society's Ancient DNA talks now online

In November I attend the Royal Society's two-day meeting on Ancient DNA. The recordings of the presentations are now available online on the Society's website:

I previously posted my notes from the meeting which might help you to decide which talks you would like to listen to:

- Day 1 at the Royal Society's Ancient DNA meeting

Day 2 at the Royal Society's Ancient DNA meeting

My personal favourites were the talks by Carles Lalueza Fox, David Reich, Johannes Krause, Greger Larson and Alice Storey.

Sunday, 8 December 2013

Setting the record straight about Sara Sheridan’s “Japanese” DNA

I’ve previously written about the exaggerated and misleading haplogroup stories provided by some DNA testing companies. BritainsDNA, which also trades under the names ScotlandsDNA, IrelandsDNA and YorkshiresDNA, has been one of the worst offenders in this regard in the last year or so. I commented previously on the problems with their story about Prince William’s supposed Indian ancestry. In May this year a Scottish novelist by the name of Sara Sheridan told the story of the unusual findings from her ScotlandsDNA test in an article for the Huffington Post. She was informed by ScotlandsDNA that, despite her family history of Jewish ancestry, she descends “from a female line called 9Na [sic] that developed 17000 years ago in the area around Japan's most northerly island and on the mainland just opposite”. 9NA is a typo in the article and does in fact refer to N9a which is a mitochondrial DNA haplogroup. While haplogroup N9a might well have arisen 17,000 years ago, plus or minus several thousand years, determining precisely where a haplogroup originated is a different matter altogether. We are mostly reliant on the mtDNA of living people to make inferences about the genetic make-up of our matrilineal ancestors, but the present-day location of the bearers of a specific haplogroup does not necessarily correlate with its ancient origins. An awful lot of migration can happen in 17,000 years! In addition, the population today will probably only represent a tiny fraction of the mtDNA diversity of our distant ancestors because so many lineages will have become extinct. It is therefore quite preposterous to propose such a precise origin for a haplogroup so many thousands of years ago. Any theories on the origins of the various haplogroups should be regarded as highly speculative and should not be taken too seriously. They most certainly should not be presented as fact as they were here.

The test Sara would have taken with ScotlandsDNA is what they now call their Standard mtDNA Test. This test looks at just 300 mtDNA markers – known as SNPs (single-nucleotide polymorphisms) – from across the mtDNA genome and costs £170.  An improved higher-resolution test known as Chromo 2 was introduced by the company in June 2013. The newer test looks at around 3000 mt SNPs and costs £189 (males also benefit from a Y-chromosome analysis from the same test). The 300 mt SNPs covered in Sara Sheridan’s ScotlandsDNA test represent just under 2% of the mtDNA genome. The new Chromo 2 test covers around 18% of the mt genome.

There are in fact many daughter branches below N9a as can be seen from the most up-to-date version of the mtDNA tree on Phylotree. However, in order to determine the sub-branch it is necessary to test many more than the 300 mt SNPs covered by ScotlandsDNA, and ideally the whole mtDNA genome (all 16569 base pairs) should be sequenced. The sub-branches are of more recent origin and can sometimes provide better geographical resolution, though there are currently not enough full mtDNA sequences available in the literature to draw reasonable conclusions.

For females the ScotlandsDNA/BritainsDNA mitochondrial DNA tests are very poor value for money. Sara Sheridan could have had her entire mitochondrial genome tested at Family Tree DNA, the market leader for mtDNA testing, for much less than the price she paid for her low-resolution and very expensive mtDNA test from ScotlandsDNA. The full mitochondrial sequence (FMS), which literally sequences all 16569 base pairs in the mt genome, normally costs $199 (about £122) and is currently on offer for $169 (about £103) in the FTDNA sale which closes at the end of December. FTDNA are currently the only company to offer a full mitochondrial sequence test direct to the consumer. The FMS test gives you the most detailed possible haplogroup assignment, which can be further refined as new sub-branches are discovered. FTDNA also have the advantage of a large genealogical matching database and the ability to join the appropriate mtDNA haplogroup project for further comparisons.

Note that although the BritainsDNA/ScotlandsDNA Chromo 2 test is poor value for females it is a useful test for males of British ancestry who wish to have a detailed Y-DNA haplogroup assignment (females do not of course have a Y-chromosome). For a comparison of the different Y-SNP tests on the market see the ISOGG Y-SNP testing chart.

When the news of Sara Sheridan’s supposed “Japanese” ancestry was first published I discussed the story with Jill Whitehead who, like Sara, has Ashkenazi Jewish ancestry from Scotland. As the Jewish community is very inter-connected it is highly likely that Jill and Sara are related within a fairly recent time frame, so Jill took a particular interest in this case. Jill is one of the pioneers in the genetic genealogy community. She had her mitochondrial DNA tested with Family Tree DNA back in 2003, and has also tested with 23andMe. Jill is a member of the Jewish Genealogical Society of Great Britain and has written several articles on Jewish genetic genealogy for the society’s journal. Jill wanted to have the opportunity to set the record straight about Sara Sheridan’s erroneous haplogroup interpretation, and has kindly provided below a much more plausible explanation of Sara's matrilineal origins:
A number of us in the DNA community are aware of the presentation of DNA results used by the company BritainsDNA/ScotlandsDNA. These have been cursory to say the least, especially in terms of unusual DNA haplogroups that are not of British origins. ScotlandsDNA advised the Scottish author Sara Sheridan that her N9a haplogroup was Japanese or Korean even though she was of Jewish Ashkenazi origins. Surely alarm bells should have rung? Instead of paying for an expensive DNA test (and ScotlandsDNA can be pricey in comparison with others) she would have been better advised to carry out a paper trail search first. 
I traced her family back through the ScotlandsPeople website, and also using the naturalisation records on the National Archives website and the JewishGen shtetl finder. I found her ancestral town of origin in Belarus within half an hour of searching. The cost was only £14 worth of credits on ScotlandsPeople. If you can get back to a naturalisation record, and bearing in mind that Scottish records show dates and places of marriages of parents (even those overseas), then it is quite a simple process to trace Jewish families (provided the name is not a common one). This was how I found my own Jewish Brown family of Edinburgh twenty years ago, before I tried DNA testing eleven years ago now. 
I could not believe the description of the N9 haplogroup given by BritainsDNA. I match up with several thousand Ashkenazi Jews on both FTDNA's Family Finder and 23andMe's DNA Relatives feature. Their tests are much more sensitive and they recognise that the Jewish sub-haplogroup of N9 is in fact N9a3. I match half a dozen people of Ashkenazi Jewish origin who are also haplogroup N9a3. There has also been quite a bit of recent international research on N9 haplogroups, and FTDNA for one always publishes recent research papers. ScotlandsDNA obviously had no idea this research existed otherwise they would have known the difference between a Jewish N9 and a non-Jewish N9. 
I reproduce below the comments I made on the Scotsman newspaper website after an article appeared in that newspaper which again described Ms Sheridan's haplogroup as being Japanese/Korean
"I come from a prominent Edinburgh Jewish family that came to the city in the 1860s. I have also been interested in genetic genealogy for over ten years having published articles on this for Shemot, the Journal of the Jewish Genealogical Society of Great Britain, e.g. their recent specialist Jewish Genetics edition. 
I was somewhat surprised to read the description of Sara Sheridan's N9a3 maternal mtdna haplogroup. The Japanese make up only one small part of N9, there are many other N9s to be found throughout the world, as shown in a number of academic genetics journals recently. I have never come across a Japanese Jew, but there is a Jewish subclade of N called N9a3 with recent origins in Poland/ Belarus/ Lithuania. In fact, a very recent academic paper from 2012 by Derenko et al from the Russian Academy of Sciences points to a series of Neolithic skeletons found in Hungary as being N9a3. 
To add to that, I have no less than four assigned third cousins on the DNA testing site 23andMe, who are all N9a3, and they are all American Ashkenazi Jews originally from Poland/Lithuania/Belarus, who are related to me some time back in about the late 18th/early 19th century. I think ScotlandsDNA needs to be more accurate in its assessment and description of haplogroups. When haplogroups were being formed in ancient times, not all humans went in one direction, they scattered east and west. That is why we have Hungarian Neolithic skeletons, East European Jews and Asian populations who make up N9 haplogroups."
Update 30 May 2015
A paper by Tian et al published in February 2015 in Scientific Reports documented four Ashekenazi Jewish individuals who were assigned to haplogroup N9A

Further reading and resources
-  A list of Jewish DNA projects provided by JewishGen

The Haplogroup N Project at Family Tree DNA

- The ISOGG list of mtDNA haplogroup projects

- The ISOGG mtDNA testing comparison chart

- The Jewish Genealogical Society of Great Britain. The April 2013 issue of the society's journal Shemot was a special edition devoted to DNA testing and provides a useful introduction to Jewish genetic genealogy.

Scientific papers
- Costa MD, Pereira JB, and Pala M. A substantial prehistoric European ancestry amongst Ashkenazi maternal lineagesNature Communications 2013; 4 (2543).

- Ostrer H and Skorecki S. The population genetics of the Jewish peopleHuman Genetics 2013; 132 (2): 119-127.

- Derenko M, Malyarchuk B, Denisova G et al.  Complete mitochondrial DNA analysis of eastern Eurasian haplogroups rarely found in populations of northern Asia and eastern Europe.  PLoS One 2012;7(2).

- Behar DM, Yunusbayev B, Metspalu M et al. The genome-wide structure of the Jewish peopleNature 2010; 466 (7303): 238-242.

- Atzmon G, Hao L, Li Hao, Pe’er I et al. Abraham’s children in the genome era: major Jewish Diaspora populations comprise distinct genetic clusters with shared Middle Eastern ancestryAmerican Journal of Human Genetics 2010; 86 (6): 850-859.

- Behar DM, Metspalu E, Kivisild T et al. Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora. American Journal of Human Genetics 2006 78 (3): 487-497.

- Behar DM, Metspalu E, Kivisild T et al. The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event. American Journal of Human Genetics 2006; 78 (3): 487-497.

- Shriver MD, Kittles RA. Genetic ancestry and the search for personalized genetic histories. Nature Reviews Genetics 2004; 5: 611-618.

Ostrer H. Legacy: A Genetic History of the Jewish People. Oxford University Press, 2012.
Abulafia D. The Great Sea: A Human History of the Mediterranean. Allen Lane/Penguin, 2011.
Goldstein D. Jacob’s Legacy: A Genetic View of Jewish History. Yale University Press. 2008.
Entine J. Abraham’s Children: Race, Identity and the DNA of the Chosen People. Grand Central Publishing, 2007.

See also
- Mitochondrial DNA testing at a new low price

© 2013-2015 Debbie Kennett

Friday, 6 December 2013

23andMe update, third party tools and alternative personal genomics companies

Following on from the warning letter received by 23andMe from the FDA, the company have now announced that in order to comply with the FDA's requirements new customers will not receive health reports "while the company moves forward with the agency’s regulatory review". The ancestry reports are not affected, and new customers will also have access to their raw data files. Raw data files can be uploaded to third-party services such as Promethease or Interpretome where you can generate your own health reports. A full list of autosomal DNA tools can be found in the ISOGG Wiki: DNA tools

The FDA is not concerned with customers interpreting their own raw data and as far I understand these third-party tools do not fall under the FDA's remit.

The health reports have only been withdrawn for customers who have ordered a 23andMe test from 22nd November onwards.  This was the date when the warning letter was received from the FDA. Existing customers who ordered a test before 22nd November will continue to have access to their health reports.

Anne Wojcicki of 23andMe has posted a personal message to 23andMe users on the company blog:

More detailed FAQs can be found on the 23andMe website:

The official press release can be found here:

Blaine Bettinger, who writes the Genetic Genealogist blog, has provided some useful commentary on the latest developments and links to other posts on the subject:

Margaret A. Hamburg, a Commissioner for Food and Drugs at the FDA, has written a letter to the Wall Street Journal in which she states that the FDA "remain committed to continuing our ongoing dialogue with the company in order to bring a safe, effective and trusted product to the market". The full letter can be read here:

It is not yet known how long the regulatory process will take but I hope that a resolution will be reached sooner rather than later and that 23andMe will once again be able to market their DNA testing service.

In the meantime if you are interested in getting your DNA tested for the health reports there are a number of different companies outside the US which offer a similar service to 23andMe. A full list can be found in the ISOGG Wiki: of personal genomics companies

All the other American companies now require that the testing is done through a doctor. However, many of the companies in other countries still offer a direct-to-consumer service. Unfortunately, none of the other personal genomics companies have the advantage of a large database and a vibrant community forum which are the biggest benefits of the 23andMe service.

For the background on the 23andMe story read my earlier blog post on 23andMe and the FDA.

Update December 2014
The 23andMe health reports are now available once again in the UK and in Canada though in a somewhat pared down form. For further information see my blog post 23andMe relaunches health reports in the UK. See also the article 23andMe launches personal genome service in the UK by Philippa Brice of the PHG Foundation.

© 2013 Debbie Kennett

Tuesday, 3 December 2013

A new exome sequencing and interpretation service from Belgian company Gentle Labs

While the spotlight has been very much on 23andMe and the FDA this last week the launch of a new high-end genomics service has attracted little attention. Gentle Labs is a new company based in Belgium. They are offering an exome sequencing service with interpretation for $1990. The results are provided through a doctor. This is from their FAQs:
Why would I pay $1990 if I can get my DNA sequenced for $99?        Some companies are offering 'insights into your DNA' for only $99. These tests, however, are only based on 0.03% of your genome (corresponding with 1.9 % of your genes). It's like reading a novel by reading a letter on every page: you won't get much of the story. These cheaper tests do not allow for accurate or complete results or interpretation: some of these tests have false negative rates of 50% or more! In fact, companies offering these tests admit this themselves. One company clearly displays on their website that "The information on this page is intended for research and educational purposes only, and is not for diagnostic use." In other words: these tests should not be relied on for any medical purposes, nor for diagnostic use.
        In contrast, our Gentle test not only offers complete coverage of all your genes, it also includes counseling with some of the world's best medical geneticists provided by Royal Doctors. Other advantages include:
        *       a free subscription service through which we will keep you informed about your DNA as science evolves
        *       free DNA data storage (so that you can provide your medical doctors access to your DNA data in case of a health issue or emergency)
        *       user friendly iPad and web apps to explore your genetic results and - in the end - yourself
The Royal Doctors have no connection with royalty but offer a network of doctors who will provide advice for a fee of one Euro per day. Their website can be found at 

Dr. Bertalan Meskó, who writes the Science Roll blog, has signed up for the Gentle service and has published an interview with Peter Schols, the CEO of Gentle Labs, which can be found here.

The launch of Gentle Labs was covered by GenomeWeb but the story is behind a paywall.

Interestingly 23andMe launched their own exome sequencing pilot programme back in 2011. Exome sequencing is the logical next step for personal genomics tests but the costs are still prohibitively high for the average consumer. It will be interesting to see what transpires in the next five years.

© Debbie Kennett

Friday, 29 November 2013

23andMe and the FDA

The big news in the genetic genealogy world this week is the announcement that the personal genomics company 23andMe have received a stern warning letter from the FDA in which they were told that they "must immediately discontinue marketing the PGS [Personal Genome Service] until such time as it receives FDA marketing authorization for the device". However,  I note that despite the warning letter 23andMe have not withdrawn their test from sale.

This is the 23andMe ad which has been shown on national TV in the US which probably sparked the FDA's action. It seems to me inappropriate to advertise such a product on the television and I can understand the FDA's concern.

There have been many excellent articles and blog posts covering all sides of the debate so I won't comment here but will instead refer you to the best resources for further reading.

Blaine Bettinger, who writes The Genetic Genealogist blog, has given his take on the story and provided a very useful selection of links to the most interesting commentary on the subject. His post can be found here. If you are interested in the implications of the FDA's actions it's well worth reading all these links.

The journalist David Dobbs has also been tracking the coverage of the story and he has summarised all the different viewpoints and provided an extensive selection of links in his blog post FDA muzzles 23andMe after talks break down.

If you only have time to read one article on the subject I recommend reading Michael Eisen's thoughtful post FDA vs. 23andMe: how do we want genetic testing to be regulated. Michael Eisen's views most closely align with my own thoughts on the matter.

It will be interesting to see what happens in the next couple of weeks. I'm not expecting the FDA to shut down 23andMe but it might be that some of the health reports are redacted until such time as an agreement can be reached. Nevertheless it's a good idea to ensure that you have downloaded your raw data and saved the health reports that are of particular relevance. Some of the health reports can be saved as PDF files. For other reports you will need to save screenshots. If you've tested with 23andMe for genealogy purposes you might also like to take advantage of the Family Tree DNA sale to transfer your results to the FTDNA's Family Finder database. The transfer will cost $49 until the end of the year (the usual price is $69).

You can read my series of articles on my own 23andMe test using the links on this page.

Monday, 25 November 2013 - a new company offering a single SNP testing service

This article is for advanced genetic genealogists who have an understanding of SNPs.
Thomas and Astrid Krahn have launched a new small business by the name of Thomas and Astrid were formerly employed by Family Tree DNA where they developed the Walk Through the Y SNP discovery programme. The new company will cater for a niche market developing custom SNPs on demand. Thomas announced the service on the Genealogy DNA list and in the ISOGG Facebook group as follows:
Expecting a flood of new SNPs from Next Gen sequencing we try to help with cleaning up the mess by offering very traditional Sanger sequencing for any marker you desire on the Y chromosome. The testing will be performed in our own laboratory.

Check out and

We don't have very many markers yet, but you can "Wish a SNP" of your choice and we'll make it available as fast as we can. We'll not limit the number of markers to 2000 or so. If you just received your NGS results, ask us for a bulk package offer by e-mail ( Let me know if you have questions.
YSEQ will focus on providing SNPs that are not available with other testing companies. SNPs will be available either singly or in panels. Family Tree DNA was previously the only other company to offer single SNP testing, but they currently do not have the capacity to provide testing for more than 2000 additional SNPs.

New SNPs can be suggested. There is a $1 fee for suggestions but this is a formal spam blocker, and it will be possible to send a long list of markers at once with a single submission.

YSEQ also plan to offer a Y-STR testing service in the near future. It is expected that this service will focus on the 300 or more STRs that are included in the next generation sequencing tests but which are not currently available to test separately from any commercial provider.

YSEQ will provide a very useful and much-needed service as we anticipate the arrival of the SNP tsunami. We are entering uncharted territory with next generation sequencing of the Y-chromosome. Custom SNP testing using the tried and tested Sanger sequencing technology will be necessary to validate the new SNPs found. Custom SNP testing will also provide a cheaper method for comparative testing of SNPs to verify their placement on the branches of the Y-tree.

I wish Thomas and Astrid Krahn every success with their new venture.

Friday, 22 November 2013

Day 2 at the Royal Society's 2013 Ancient DNA Meeting

This is my second and final report from the Royal Society's Ancient DNA Meeting. See my previous post on Day 1 at the Royal Society's 2013 Ancient DNA Meeting for the full details of the meeting. As before, the accuracy of my notes and my interpretation of the lectures is not guaranteed, but I hope that some people might find the information useful until such time as the audio recordings become available.
The room starts to fill up as delegates arrive for the start of Day 2.

Robin Allaby, University of Warwick, England 
Using archaeogenomic and computational approaches to unravel the history of local adaptation in crops
Most of the plant studies to date have been on crop evolution. New computational approaches are now being used.
Barley degrades after 350 years in North African climates.
We don’t expect to see much ancient DNA from barley after about 4000 years.
There has been a shift in emphasis  from "what". Scientists are now looking at how the crops got domesticated and how they adapted to new latitudes.
Plant exploitation by humans has been going on a for a long time before the Younger Dryas.
He showed us models which suggested that plants which have had a rapid adaptation have a lower survival rate.
Does next generation sequencing work with low latitude samples?
He shared his research on samples from the Qasr Ibrim archaeological site in Egypt. The site had been occupied for about 3000 years by five different cultures. This is a very dry site and is particularly good for preservation as there are few bacteria found in the samples. The barley still looked edible after 1000 years.
They found evidence that a new type of barley was introduced in this region during the Christian period coinciding with the Crusades.

Alice Storey, University of New England, USA
A multidisciplinary view on the domestication and dispersal of the chicken
Alice was clearly passionate about her subject and gave a very interesting and illuminating talk. I never thought I would find chickens so interesting! As she pointed out, chickens have been transported by humans and by studying chickens we can answer questions about human history. Many of the very valid points she made were just as applicable to other disciplines.
 “It is a cursed evil to any man to become as absorbed in any subject as I am in mine”. This quote has been attributed to Darwin but the source is not known. Can anyone help?
Chicken research goes back to Aristotle (384-322 BCE).
Chicken research is 20 years behind ancient DNA research into cattle and horses.
The context and provenance are important. Where something comes from and how it got there matters. “Context isn’t always what it seems”.
“The past is a palimpsest assemblage”.
A good example of the problem is the paper by Harris et al 2013 looking at chickens in Santa Cruz where they found that there had been lots of movement of chickens.
There are currently 871 chicken sequences but only 18.5% come from the wild. Many of the samples have come from zoos but they have no provenance.
People move animals around. They are portable wealth. There is a documented transfer of chickens from India to China in 1400 BC.
If you look at a modern DNA signature you are getting a mixture – an omnishambles.
Multiple DNA signatures in chickens.
Contemporary flocks are 80% foreign.
Only 17 whole mtDNA genomes.
Other samples have sequenced 500 bases pairs in control region.
The earliest accepted domestic chicken remains have been found in Northern China.
Over 30 candidate domestication genes have been identified.
Samples can be radio-carbon-dated to fix age.
There is one full chicken genome but we can’t read it properly.

Greger Larsen, Durham University, England
Testing the chronology of domestication genes using ancient DNA
This was by far the funniest and most entertaining talk of the conference. Larsen told us that Ian Barnes is much funnier than he is. However, Larsen can ride a bike and Barnes can't! Ian Barnes was not at the conference and I have not yet had the opportunity to hear him speak so I was unable to make comparisons.
Domestication genes are genes that control traits during the initial process and are typically fixed. Improvement genes are variable amongst domestic populations.
Chickens in the western world all have yellow legs. It’s always been assumed that because of the wide distribution of yellow legs they evolved early and it was thought that the trait was favoured by early farmers. Ancient DNA has now shown that this theory is wrong as the genes for yellow legs are not found in ancient DNA samples. Ancient DNA reveals a lack of fixation.
The reviewers (especially that pesky Reviewer Number 2!) had problems believing the research because it went against accepted thinking. Paper after paper has shown that a wide present-day distribution correlates with early evolution.
He had the audience in stitches by speculating on how his research might be received by the media:
Daily Mail: "Shocking waste of taxes on study that proves all 100 million UK chickens are dirty foreign birds".
Editors of high profile journals: "Chickens are first and best domesticated animal". (Extra brownie points for getting two superlatives into one paper!)
BBC: "Yeti proven to be giant chicken". 2bps of 16S perfectly matches a chicken.
 “The past is a different country”. The vast majority of variation has gone extinct. We can’t see it in modern-day populations. He showed here a slide showing the phylogenetic trees for a number of different animals. The trees were based on both modern populations and ancient DNA research. Large parts of the trees included branches found in ancient DNA that are now extinct in modern populations. One of the trees (bears?) was particularly striking as about 90% of the tree was now extinct.
Don’t make assumptions based on modern populations however obvious they might seem.
It has always been assumed that when something is fixed in a single breed this is a sign of early origins. Strong selection leads to fixation and is followed by geographical proliferation. There has been study after study in animals which seem to prove this point. Larsen’s chicken research now shows that this is not always the case. There is no link between modern ubiquity and ancient origins. Assumptions based on modern data need to be re-tested. The old papers need to be reinvestigated.
There are temporal changes in allele frequency. Bottlenecks are insane.

Comment from Alice Storey: There are good written records for chickens and with a search through the literature it might be possible to determine the date when yellow chicken legs were first reported as a result of crossing experiments. There do not appear to have been any reports of yellow legs before about 1820.

Dan Bradley, Trinity College Dublin, Ireland
Cattle and codices – aDNA in bone and parchment
There are two main types of cattle: Bos taurus and Bos indicus. Genetic data show that the two species diverged hundreds of thousands of years ago. It is thought that there were two independent domestications.
Next generation sequencing is now used for ancient DNA research in cattle. There are lots of sequence errors.
Whole genome mtDNA resolution gives greater clarity.
Ancient DNA fills out the phylogenetic history and helps with the calibration and the mutation rates. Use time-stamped variants to calibrate the tree.
[Autosomal] microsatellite genomic data also show that the two cattle species have very divergent alleles.
It’s now been shown that both species share a common ancestor.
Manuscript parchment and ancient DNA analysis.
Parchments are ubiquitous in the historical record from the 13th to the 18th century.
Parchments can be directly dated. They are robust, well preserved and valuable documents and are a good source of domestic DNA.
The ancient DNA standards suggest that we should “Do it right or not at all”. Dan Bradley says we should “Do it all or not at all”. Do it all (high-coverage next generation sequencing) is now within our reach

Comments from audience
David Reich: Have you thought of using linkage disequilibrium?

David Lambert, Griffith University, Australia
Bursting the limits of time: ancient penguin genomics
He opened with a mention of Martin Rudwick’s book Bursting the Limits of Time which has greatly influenced him.
Georges Cuvier developed the first test of evolution 60 years before Darwin.
Jean-Baptise Lamarck is the father of the idea of evolution. He came up with many of the key principles 50 years before Darwin.
The most recent common ancestor of penguins lived 20.4 MYA (million years ago) (17.0-23.8 MYA).
The current population of Adélie penguins is 10 million. They only nest in ice-free areas. There is a lack of genetic differentiation, but there is a lot of mtDNA diversity.
The microsatellites (autosomal?) in penguins get longer over time.
Millar and Lambert 2008 PLOS article: Mutation and evolutionary rates of Adélie penguins from the Antarctic.
There are 20 complete mtDNA genomes. Eight of these are from ancient DNA. There are 26 modern genomes at 18-30x coverage.
There is a low level of differentiation of colonies all around Antarctica. There are 35-40 ancient genomes at 1-4 x coverage (mtDNA and nuclear genomes).
Penguins are an isolated population. They live in Antarctica and co-exist with only two other species. Consequently there are major opportunities for population genome studies aimed at understanding evolutionary processes.
Population genomics will enable us to better understand the genomic processes that underlie evolutionary changes (eg, mutational mechanisms).

Ludovic Orlando, University of Copenhagen, Denmark
Digging out the deep evolutionary past of equids: towards really ancient genomes
There is hardly any ancient DNA for the period from 126 KYA (thousand years ago) to 781 KYA. We have 16 base pairs from a bear in Southern Spain.
He described the methodology used to date the equus DNA extracted from a find in Thistle Creek in the Yukon Territory in the South Klondike. The equus was preserved in the permafrost.
The researchers deployed single molecule sequencing using machines from a company called Helicos Biosciences. The company has since gone bankrupt.
Paper: True single molecule DNA sequencing of a Pleistocene horse bone 1.3x – 3.4x.
Ancient DNA is short and fragmented.
Paper: Improving ancient DNA read mapping against modern reference genomes.
There are 83 complete mtDNAs of modern horses available.
Paper Achilli et al PNAS 2011: Mitochondrial genomes from modern horses reveal the major haplogroups that underwent domestication.
How to detect the degree of degradation.
The authors described the methods they had used to date the horse.
This talk was highly technical and a lot of it was above my head. Perhaps others who are more knowledgeable than me will be able to provide a better summary.

Laura Parducci, Uppsala University, Sweden
Ancient Plant DNA of Nordic environments
Plant mtDNA is very different from that of animals and has a very low mutation rate.
Ecological niche modelling.

Michael Hofreiter, University of Potsdam, Germany
(previously at the University of York, England)
The future of ancient DNA
“Predictions are difficult, especially about the future.”
We will not be able to extract any dinosaur DNA.
Homo floriensis (Hobbit) DNA also seems highly unlikely.
There are now lots of genomes and many more in the making.
Sanger sequencing was used until 2005.
454 sequencing was introduced in 2005.
Illumina next generation sequencing started in 2009.
We can’t do de novo assembly of a genome with next generation sequencing. You have to map to something.
There is not just one past, but many pasts – many many time slices.

Questions from the audience
I wasn't sure if I correctly understood the question but Mark Thomas asked something along the lines that if a sequence were generated with current technology would it actually work in theory if it could be used to create a new being. The answer was no, presumably because sequences are not 100% accurate.
I asked about full Y-chromosome sequencing and whether or not it might ever be deployed in ancient DNA research. The answer was that it is the worst locus to analyse. It is difficult to analyse because of all the repetitive sequences. I would like to think that Michael Hofreiter might be wrong and that the impossible will one day be possible!

Other news from the meeting
There is a new Ancient DNA Community on Google+ for both academics and members of the public.

Bruce Winney told me that, fingers crossed, he hopes the paper on the People of the British Isles Project will be submitted in the next few weeks.

Turi King has nearly finished the analysis of Richard III’s DNA. A paper won’t be submitted until next year.

As I was compiling this post an important new paper appeared online in Nature entitled Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans. The authors have sequenced the draft genome “of an approximately 24,000-year-old individual (MA-1), from Mal’ta in south-central Siberia, to an average depth of 1×”. They claim that, to their knowledge, “this is the oldest anatomically modern human genome reported to date”.

The recordings of all the lectures from this meeting are now freely available on the Royal Society's website.

See also
Day 1 at the Royal Society's 2013 Ancient DNA Meeting

© 2013 Debbie Kennett

Thursday, 21 November 2013

Day 1 at the Royal Society's 2013 Ancient DNA meeting

I spent two very interesting days this week attending the Royal Society’s meeting on Ancient DNA: the first three decades. Recorded audio of the presentations will be available on the Royal Society’s website at some point and the papers will be published in a future issue of Philosophical Transactions B. While at the meeting I made notes during the talks, and I thought that until the recordings have been uploaded to the website these notes might be of interest to those who were unable to attend the meeting. These notes are not intended to provide comprehensive coverage, and I only jotted down items that I personally found of particular interest. My primary focus is on the genealogical applications of DNA testing, and my interests will, therefore not necessarily coincide with those of other researchers. Many of the technical and scientific details of the talks were well outside my expertise. The accuracy of my notes and my interpretation of the lectures is not guaranteed, but I hope that some people might find the information useful.
The Royal Society in Carlton House Terrace, London SW1 - 
the venue for the Ancient DNA meeting.

Full details of the meeting, along with speaker biographies, can be found on the Royal Society’s website. The abstracts for these talks have not been made available on the website though they are all included in the programme which was issued to attendees.

A related satellite meeting is taking place in Buckinghamshire and finishing tomorrow. The speaker’s biographies and the abstracts are available on the website for the this meeting. I was not able to attend this event but I hope that other attendees will provide reports in due course.

Erika Hagelberg, University of Oslo, Norway
Ancient DNA: the first three decades
The first article on ancient DNA was published in 1984. It was a report of the cloning of a small piece of DNA from the skin of an extinct equid (a member of the horse family) that had been preserved in a museum.
The second important ancient DNA paper was on molecular Egyptology.
A lot of the early research centred on Allan Wilson’s lab
In the early days ancient DNA testing was done on the workbench without any protective clothing.
PCR [polymerase chain reaction – a process for amplifying DNA] was introduced in the late 1980s.
The first PCR machine was made with a kettle.
The late 1990s saw the development of standards of authenticity. Hagelberg felt that the new standards stifled research and open discussion.
The big technological advances in recent years have been in bioinformatics, contamination filters and next generation sequencing.
The early studies on ancient DNA (magnolia leaf, an insect embedded in amber) are now not considered very credible. It is also difficult to reproduce these early studies.
The first ancient DNA newsletter was published in 1992.
The limit for ancient DNA was originally thought to be 5000 years.
1 March 1990 Angel of Death newspaper article on the DNA of Mengele. This was the first use of DNA in forensics.
The 1990s also saw the DNA analysis of the remains of the Russian Imperial family. Some people disputed the results.
1994 Dinosaur DNA turned out to be human DNA
1997 Ryk Ward and Chris Stringer publish a paper in Nature in which they outline standards for ancient DNA research
2000 Cooper and Poiner letter in Science. “Do it right or not at all”
Hagelerg said that this was often interpreted as “Do it with me or not at all”.

Christine Keyser, University of Strasbourg, France
Past human populations in Eurasia
Keyser reported on an ancient DNA study of samples obtained from 150 graves in Yakutia  in Northern Siberia.
146 bodies were found. They were frozen at the time of discovery. Genetic data was obtained from 130 bodies.
Optimal ancient DNA is obtained from bone.
Smallpox found in Yakut graves – identified by histology.
Y-chromosome analysis was done using a Y-filer kit (17 Y-STRs). There were 20 different haplotypes. A strong founder effect was found with one haplotype shared by 29 males (46%). They went up to 23 STRs on these samples but found only three differences in the 29 males.
For the mtDNA analysis they tested HVR1 and the coding region. There were 44 different mtDNA haplotypes (n=130) with haplogroups C and D predominating.
IrisPlex and HirisPlex were used to determine hair and eye colour. Six SNPs used to detect eye colour. Brown hair and brown eyes.
SNP testing. N1c1 was the predominant Y-DNA subclade.
Full mtDNA genomes sequenced. D5a2a most common subclade.

Anne Stone, Arizona State University, USA
Impacts of colonisation in the Americas
Anne Stone was invited to speak at the last minute after the scheduled speaker, Ripan Malhi, had to withdraw. Malhi’s talk was to be on the subject of “The evolutionary history of Native Americans”. There is a summary of his planned talk on Science Daily in an article entitled Ancient, modern DNA tell story of first humans in the Americas.

Stone's talk focused on the impacts of colonisation in the Americas.
The initial colonisation of America took place between 18,000 and 25,000 years ago.
The post-Clovis theory of colonisation is dead.
The major part of Stone’s talk focused on the Salesia mission in Tierra del Fuego.
TB was the leading cause of death at the mission. No genetic evidence of TB found in her study.
Targeted enrichment to get full mt genome.
The genetic evidence shows that TB was already in animals in America before humans arrived.
Hershberg et al 2008 paper on the biogeography of M.tuberculosis.
The genetic testing of Native Americans depends on view of individual tribal groups.

Questions from the audience
Q What is the evidence for the pre-Clovis theory?
A The genetic evidence for pre-Clovis colonisation of America is based on signals of expansion. Human coprolite data is also pre-Clovis [coprolite = fossilised poo!].

Helena Malmström, Uppsala University, Sweden
The Neolithic transition in Scandinavia
Farming started 12,000 years ago in the Near East and 7,000 years ago in Northern Europe.
In Scandinavia hunter gatherers and farmers co-existed for a period of about 1000 years.
The hunter gatherers (Pitted Ware complex) and the farmers (Funnel Beaker complex) had different maternal lineages.
Haplogroup U was found at the highest frequency with U4 top of the list.
Autosomal SNP analysis showed that the Neolithic hunter gatherers differ from modern Europeans and were most like Sardinians and Basques.
[DK note: For background see the 2012 Nature News article by Henry Nichols Ancient Swedish farmer came from the Mediterranean and the 2009 paper by Malmström et al.] 

Carles Lalueza-Fox, Institute of Evolutionary Biology (CSIC-UPF), Spain
Neandertal paleogenomics and the El Sidrón cave
This was an excellent and sometimes humorous talk on the exciting findings from El Sidrón cave in Asturias, Spain.
Lalueza-Fox started by sharing a number of illustrations showing how our perception of Neanderthals has changed over time. We now know that they used language, and they lived in family and social groups. The final picture representing the current thinking showed a picture of a Neanderthal mother and child looking not much different from modern humans.
See also the modern reconstruction picture shared by @mjpallen on Twitter.
 Laleuza-Fox took us on a photographic tour of El Sidrón cave. A group of Neanderthal individuals were found in this cave. They had been trapped in the cave after a rock fall and their DNA provides a snapshot in time of a Neanderthal social group.
Complete mtDNA genomes were obtained.  Three different Neanderthal mtDNA haplogroups were found which Laleula-Fox has labelled A B and C. 7/12 were A. 1/12 was B and 4/12 were C. Three adult males had the same mtDNA but the three adult females had different mtDNA. This is indicative of patrilocal reproductive behaviour.
There were cut marks on all the remains – evidence of cannibalism.
Laleuza-Fox et al 2007 paper in Science. Some Neanderthals had red hair

David Reich, Harvard Medical School, USA
Insights into population history from high coverage Neandertal and Denisova genomes
[DK comment: Why do Americans spell Neandertal without an H but pronounce the word as though it does have an H. Why do Brits spell Neanderthal with an H but pronounce it as though it doesn’t have an H?]
This was the highlight of the first day’s talks. It was delivered at breathtaking speed, barely allowing us time to digest the content on the slides. I would have liked to have had a pause button so that I could stop and look at everything again in more detail.
Neanderthal gene flow is about 2%:
1.72% in Europeans
1.89% in East Asians
(Confidence intervals were provided but the slide disappeared to quickly for me to note them.)
Autosomal DNA analysis used a recombination rate of 10cM per 10 generations, 100 cMs per 100 generations. I spotted Graham Coop’s name on this slide but wasn’t sure whether Reich was citing the paper The geography of recent ancestry across Europe 
We now have Neanderthal sequences from three different locations: Croatia, Russia and the Altai Cave in the Altai Mountains in Siberia. This is the cave where Denisovan DNA was found but the latest analyses show that Neanderthals also lived there.
Archaic split 77-114 kya.
There were multiple gene flows.
In the original Denisovan study DNA was extracted from the little finger of a young girl. The samples date back more than 50,000 years. DNA has now also been extracted from a molar.
1.9 fold coverage of genome.
Denisovans are more closedly related to Neanderthals than to humans. Their mtDNA is twice as deep compared to Neanderthals than humans.
Denisovans are closely related to people from New Guinea. New Guineans have 4.6% Denisovan and in addition 2.5% Neanderthal.
2013 paper to be published on Altai Neanderthal found in same cave. Sequencing done at high resolution 52x coverage.
The archaic populations have a very low level of genetic diversity. The Altai Neanderthal are highly inbred.
Reich showed us a number of slides exploring a number of hypotheses he investigated on the relatedness of Denisovans to Neanderthals and humans. He concluded that “Denisovans harbour ancestry from an unknown archaic population unrelated to Neanderthals and modern humans”.
[DK note: This finding was anticipated by Graham Coop in his Haldane’s sieve blog post Thoughts on: The date of interbreeding between Neandertals and modern humans.]
New research has shown that Denisovan DNA is now found in East Asians. See the Cooper and Stringer 2013 paper: Paleontology. Did the Denisovans cross Wallace's Line?
Conclusion: gene flow between diverged humans was common in late Pleistocene and there were five events.

Questions from the audience
Q Does this mean humans copulated with Neanderthals? A Yes!
Q Does this mean humans fancied Neanderthals? A Yes!

Reich’s talk seemed to be the one that was attracting all the interest from the media. Ewen Callaway, the reporter from Nature, was at the conference and he has already written an article for Nature Breaking News which can be found here. There is further coverage from Michael Marshall in New Scientist.

[DK note: The abstract for this paper also mentions Neanderthal X-chromosome ancestry. I don't know if I missed the mention of the X-chromosome in this high-velocity presentation or if it was perhaps not covered. Here is the relevant extract from the abstract: "The average Neandertal ancestry on the X chromosome is about a fifth of that in the rest of the genome. It is known from studies of many species that genetic variations causing hybrid sterility concentrate on chromosome X. This is consistent with Neandertals and modern humans having been on the edge of biological incompatibility when they met and mixed.]

Johannes Krause, University of Tübingen
Ancient pathogen genomics: what we learn from historical diseases
The Black Death killed 30-50% of the population of Europe. It probably originated in China. Yersinia pestis has the biggest diversity in China.
99% of pestis genome sequenced at 30x coverage.
Yersinia pestis MRCA within last 4000 years.
There is nothing in the genome to explain the high mortality rate.

Christina Warinner, University of Oklahoma, USA
A new era in paleomicrobiology: microbiomes
If you go by the number of cells in our body we are 90% bacteria.
The bacteria in our bodies weigh around three pounds.
The bacterial genome is also known as the accessory genome.
There has been a 38-fold increase in the number of known bacteria in the last seven years.
Best estimate before NGS is 500 species of bacteria in mouth. After NGS, 19,000!
You can get lots of DNA from calculus.

[DK note: I'm afraid I was flagging at this point after a 5.15 am start to my day and only four hours' sleep. This talk was highly technical and much of it was over my head. The take-home message from the final talk was that this is an important emerging new field for the study of ancient DNA.]

The recordings of all the lectures from this meeting are now freely available on the Royal Society's website.

See also
My notes from Day 2 at the Royal Society's 2013 Ancient DNA Meeting

© 2013 Debbie Kennett