Respecting Synthia

since 23andme recently changed almost unnoticed their terms of subscription, most of V3 chip accounts after cancelling will turn into a sort of demo-accounts with only access to their rawdata.
When Jim McMillan put together a virtual person as a reference for a northwesteuropean person and I added a face to that, we both installed a demoaccount at 23andme and I even asked the staff for the possibility to upload Jims data to their database - as usual with no response.
Well, I have the impression, that 23andme is losing their capacity to differenciate between real and virtual people.
Installing a facebook account for Synthia Zaender, as I called her, I used the following text for my invitations:
 
"hi,
I'm Synthia, a synthetic woman, who's genome (about 570000 basepairs) was  compiled by Jim McMillan, using the most common segments,  he could find in the databases of 23andme testees of european descent. According to my snpedia/promethease results, as he could define, I'm light skinned, prone to freckling, lactose tolerant, with type A blood, red or light blond hair, blue eyes, would pick up 4 IQ points if breast feed, and more.
Following this, Hartmut Zänder made my portrait, including my possible mtdna haplogroup H1.

 

You can see my comparisons at:
http://www.box.net/shared/oskds8h9by"

This is, was Synthia ( not the real me! ) got today at her account:

"You really are as fascinating as you think you are.

23andMe in 2011: Helping Customers Tell Their Stories
   
Dear Synthia,
The 23andMe team made great strides this year in our mission to bring the world of genetics to you. Thank you for taking part in the personal genetics revolution, and making this possible. We take inspiration every day from the stories you share about the positive impact of our unique service. Here are the highlights of 2011, including some of the most inspiring of these stories:

New and Updated Content
   
    * Our scientists selected the highest quality information from thousands of research articles to deliver 78 new and updated reports about your health and traits.
    * Along with extensive reports on diseases such as Alzheimer’s disease, we delivered “conversational” reports — for example describing how your genes might impact your coffee habit.
    * Our blog The Spittoon kept you current throughout the year on the latest discoveries in genetics and more.
Karen Durrett may have saved her life when she talked to her doctor about her increased genetic risk for breast cancer.
   
New Tools
    * Our improved Relative Finder tool connected more family trees than ever before, with most members seeing more than 250 new relatives.
    * The new Neanderthal Ancestry feature let you explore your caveman roots.
    * You can now team up with your family on your Family Health History to get a more complete picture of your health.
    * New community tools made it easier to share your stories and connect common interests.

Neil Schwartzman used 23andMe's Relative Finder to connect with the sister he never knew he had.
   

New Research and Discoveries
    * Thanks to the contributions of 23andMe members, we published a groundbreaking study on the genetics of Parkinson’s disease.
    * Our Roots into the Future initiative, a revolutionary study exploring the impact of genetics on health in African Americans, enrolled thousands of participants.
    * We continued to support research for rare diseases by launching the myeloproliferative disorders community.
    * We added 15 new Research Discoveries, on topics silly to serious, driven by the participation of people like you.

Jim Wong joined the Parkinson's Community and fought back against his Parkinson’s.
   
23andMe brings the stories in your DNA to life. We can't wait to add exciting new chapters in 2012.

Happy New Year!

The 23andMe Team           
   
Because no one is just like you.

Homo floresiensis

Dienekes today pointed to a new study about the Flores dwarfs:
http://dienekes.blogspot.com/2011/11/homo-floresiensis-dramatically-dwarfed.html

I couldn't find a foto about this, so I post a painting, I did 6 years ago:
"Ebu Gogo", Acr/canvas, 112 x 200 cm, 2005

http://zaender.com/malerei/2005/ebugogo.jpg

My personal "Ariernachweis"

The dreams of ethnic or national purity sometimes produce terrible consequences. European arrogance, based both on a vague feeling of racial superiority and a dogmatic interpretation of Christian beliefs led to this disastrous mixture of a theology without a possible argument and a biologistic view without a proof.
After a millennium of rather peaceful coexistence, grounding in roman tolerance towards different populations and religions, the medieval area developed the frameset of a North European anti-Semitism, leading to crusades and first in Spain to a law with the name “limpieza de sangre” at the end of the 15th century, which should exclude all Jews and Maures from high social positions. This pregenetic concept of a purity of blood ( with all its social hierarchy implied ) was still virulent, when the National Socialists in 1933 started to demand a proof for a pure German descent – the Ariernachweis. He caused a hype for genealogy until the end of WW2. It seems perverted, but after all that physical and cultural destruction the Ariernachweis today often is the only source for a genealogical startup. Without those records, collected by my grandfather before his public job as a teacher I would know nearly nothing about my ancestors.
80 years ago no genetic instrument was at hand to determine any Ashkenazi admixture, so mere declaration about the baptisms of the grandparents was mainly demanded. This procedure could lead to absurdities, since any conversion of someone of the Great-Greatparent generation could not be considered. In genetic terms we would call this a mismatch. Today with autosomal comparisons we have better instruments at hand to look for any Ashkenazi connection.
Within the tools of 23andme we can look for several indicators, the total amount of genetic cousins, the occurrence of specific haplogroups, the number of connections with declared Jewish grandparents in Ancestry Finder, the number of relatives in Relative Finder. My results look like this:

Up to a dozen connections in Ancestry Finder is what seems to be usual in German data files, as far as I can see. It is either background noise or the amount of admixture we should expect after such a long time of coexistence. Two Jewish haplogroups in Relative Finder does not look like recent relationship either.
This picture changed, when the results of my mother came in. One generation further back seem to open a new window:

She has less matches in Ancestry Finder, what could mean, that I have possible additional connections on my fathers side, but she encounters a complete different situation in Relative Finder. We have only one Jewish cousin in common ( N1b2 ), but I gathered all available information together about the provenience of her cousins ( some appear in AF too ) and was even able to locate most of her matches in a cluster on chromosome 7. The grandfather of the 26,9 cM match left Volhynia in 1912 and went to Buenos Aires.

The practice of declaring the Ashkenazi background of grandparents looks a bit similar to the above mentioned Ariernachweis, but the goal is a different one, not discrimination, just pure information.

Köln, Oct 2011

 

Mei jrine Kusine 2: A genetic Tsunami?

Again I’m looking for an illustrative explanation concerning the simple fact, that people with an Ashkenazim background have about ten times more genetic cousins than me. The two main reasons, cited in countless forum postings are heading both historical developments and a higher inbreeding ratio. This always sounds logical, but is nevertheless hard to understand. So here it goes with a personal visual approach!
In Cologne we have just started to explore a new excavation site in the old Jewish quarter, built in the 12th century, when the town expanded toward a muddy Rhine arm. They already found fine jewellery, burnt remains of the Bartholomew night and even a big Jewish romance of chivalry, containing a lot of erotic adventures. At that time the members of the Jewish community along the Rhine valley named them self  Ashkenazim.  There are thought to be about 25000 in the cities of Speyer, Worms, Mainz and Köln. Beside their ritual language Hebrew they spoke a German medieval dialect as everyday language.  In the dynamics of the beginning crusades with all its hate propaganda they were pushed by west-European Christian anti-Semitism to leave their homes and move more and more eastwards, enriching their language with Czechish, Polish and Russian idioms, thus developing Yiddish.
There are almost 2000 years of Jewish presence in Europe. In 321 Caesar Diocletian confirmed a declaration from Cologne, demanding, that members of the Jewish community now should have the right to join the city government, what exactly means, that there must have been a considerable amount of Jewish citizens with enough cultural and financial power to compete in a city of about 30.000 people. The soldier camps along the roman LIMES ( including Mainz, Speyer, Worms and other) are exactly the same as mentioned to be Jewish centers later, what makes me believe, they had been here since roman times. Romans lived in the Rhine valley for about 500 years - enough time for Jewish merchants and families to find a way up north.
While the Ashkenazim were forced to emigrate eastward, parts of their Sephardic distant cousins joined them, leaving Spain and Portugal. Later on others became the first to cross the ocean for the Americas. They reached New Amsterdam via Brazil in 1654. This first immigration wave was followed by a German one after 1840, before the main wave started around 1880,  bringing until 1924 more than 2500000 eastern Jews into the US. This seems to be the wave, whose genetic echo we encounter nowadays.
But this alone cannot explain the amount of matches, so I wanted to have a closer look on what is called the “inbreeding ratio”. Traditional genealogy already gave definitions, explaining the simple fact, that our binary ancestor tree (doubling in each generation) would produce an absurd situation, outnumbering the world population after enough generations. The solution for this paradox is called implex or pedigree collapse or Ahnenschwund. It means that further back in time some ancestors must appear in several positions, that there must have been more and more cases of cousin or uncle-niece marriages. I do not want to focus on the different reasons for this phenomenon, but head for its principal genetic implications, which are to illustrate. The usual pedigree tree gives us eight great-grandparents, thus shrinking the genetic partition of each to about 12,5 % of a great-grandson or daughter after three generations.
This is what it looks like in the light of a cousin or uncle-niece marriage. As one can easily see, a cousin marriage reduces the number of great-grandparents to six and produces two generations of same percentage, while marrying an uncle only needs four great-grandparents.

Mei jrine Kusine 1

The main goal of the regband-project was a visual one from the very beginning. How does it look, when multiple matches cluster together, are we able to detect visual pattern, that allow additional interpretation to usual algorythms. Three forms of clusters are quickly distinguishable and seem to be related to different time-frames. Independent from centiMorgan values a cluster, spreading his matches in a wider field, a looser composition ( soft edge ) looks definitely very much younger than those, who have already developed one sharp start- or ending point (hard edge ). Smaller clusters of only three to five MB length with sharp start AND endpoints can perhaps be contributed a considerable age. They are probably real ancestry bands, shared by people of very distant and different countries.
We all have still to learn about the nature of our IBD segments and it would be helpful to clearly distinguish between individual familiar matches, very old ancestry matches, shared by most Europeans and regionally composed stretches, which should have been enriched by specific motives, shaped through natural geographic, ethnic or religious borders up to the complete isolation of a small gene pool.

Ten Ancestry Finder screenshots of Ashkenazim, merged in one.

This is true of the Ashkenazim and knowing, that they show up with about ten times more relatives than a common European, I have to admit – I was much afraid of looking at the first inevitable CSV-files from Ancestry Finder for the regband project. I should have known! At the end of 2010 there were around 300 matches in my own AF-file, the usual range for a continental European. In files of colonial or Finnish descent this number could double, but encountering more than 3000 matches really caused more than one problem. Until then the checking of those usual files took one hour to a whole evening, but now I was busy for more than a week. The threshold problem, the team of 23andme faced in the beginning, showed up as well as a logistic one – namely the difficulty of a clear definition for soft or hard edge clusters. Scrolling up and down an excel-file cannot reveal the true shaping of different clusters, this can only the visual detour of a handmade collection in a chromosome style sheet. Since I don’t work with a computer program, it was impossible and too time consuming to head for all chromosomes, so I simply show the given problems exemplary in the picture of the smaller chromosome 15. On the left side we see a collection of single matches, as explored in two AF-files of full Ashkenazim descent, on the right side the compilation of all the other files.

Historical ancestry painting 1

German dreams of Namibia:

Triangulation 4 ( reflections )

Complications in HIR-comparing

Gedmatch, the new comparison tool of John Ohlson offers the opportunity to triangulate ones matches, what simply means, that one can proof, if cousin A also matches cousin B. Unfortunately this seems to be more complicated than expected at first glance. When I perceived the first bud of a multiple cluster of matches in the early beginnings of Relative Finder, I immediately sent out emails to my cousins, pointing to the possibility, that they could also match. No reply! Probably I share this naïve calculation with a lot of other people – if I share a half identical region with cousin A and B, those two should share the same segment too, what is simply wrong!

Let’s pretend, we could represent an IBD segment of an MRCA, a most recent common ancestor with a simple icon and let’s have a closer look on the logical possibilities on triangulated matches.

Cousin A has on the paternal side a segment in common with cousin C, on maternal side a HIR with cousin B, but cousin B and C have nothing in common.

A similar situation. Cousin A has on the paternal side a segment in common with cousin C, on maternal side a HIR with cousin B, but now cousin B and C share a third common ancestor on different stretches of the chromosome. This looks like a perfect triangulated match, but is not.

This is a perfect triangulated match, since the homozygotous status of cousin A does not allow any uncertainty.

It seems, that a given HIR from cousin A can be traced in the complete genome even, if parts of the sequence are removed from paternal to maternal side, like the example of cousin B shows. The multiple shifting of cousin C is of course not very probable, although such events sometimes occur on the borders of a HIR ( fuzzy boundaries ). That’s why members of a younger generation can encounter a longer segment than their parents.

Triangulation 3 (reflections)

My Polish cousin

In spring 2010 the clients of 23andme encountered a new tool - Ancestry Finder. It shows a possible Ashkenazi heritage, as all participants are asked to list especially this item plus the original countries of their grandparents. As the published experiences in some forums show, I was not the only one to be astonished and surprised finding a lot of never expected countries among all those matches with a lowered centiMorgan threshold. A closer look should help to understand this phenomenon. Defining my country of origin had been a problem, since all my German ancestors lived in nowadays Poland. The probability of meeting distant cousins from Poland or other countries in the neighborhood is rather high. This is confirmed by Davidskis and Dienekens diagrams, where I’m placed at the outer most eastern edge, even behind some Polish and Hungarian people (DE1 & DOD219). So a reciprocal genetic influence has to be considered as normal for a country of origin and its neighborhood. But this does not explain matches with countries like Italy or Portugal or Mexico. This question depends on traditional genealogical framesets. Checking the own ascending tree reveals a triangle like pyramid, standing on its top and doubling the number of ancestors in each generation.

The visualization of such a tree leads like a time machine through the generations into time layers of complete different political and social conditions. People had dozens of descendants, one half of them dying early, more than 90% lived on the countryside, mostly starving during the small ice age, the disastrous 30 year war and after. The pressure to leave the own country to create new colonies somewhere in the East or to head unknown continents was a lot higher than today. Most of 23andme users are US citizens with a colonial or more recent immigration background. Matching one of these makes clear, that a second ancestry pyramid is necessary to allow a plausible comparison.

Two different ancestry pyramids only need one common ancestor some 5, 7, 10 generations ago and of course we can encounter in the second pyramid also people from co-emigration or immigration countries, not belonging to one’s own ancestry. This is the reason not to list immigration countries in my Regband project. Of course one has to bear in mind, that this is based on a pure European perspective.
One additional calculation is to mention:
If I have as a German or Polish citizen around 100 relatives in a dataset of about 70000 clients, I can expect more than 2 million cousins in a global North European context. Turning an ancestry pyramid around and setting our most recent common ancestor on top, thus having an irregular triangle reveals, that we can expect the same amount of descendants as above, following all possible lines. In this illustration I only marked two of these lines.

Triangulation 2 ( reflections )

My Chinese cousin

Comparing even two identical mitochondrial Full Genome Sequences cannot proof a possible familiar relationship, since the last mutation may have occurred 2 – 5 thousand years ago. Y-chromosomes are mutating faster and can scratch on the timeframe of genealogical interest, but are also not easy to handle possible relationships. Only autosomal comparing can reveal stretches, pointing to a common ancestor. Beside the mere information about the genetic distance, start and endpoints of the predominant smaller HIR’s, “Ancestry Finder” lists all the countries, our grandparent generation comes from plus a possible Ashkenazi heritage.
At first glance almost everybody will have been surprised to find countries listed, no one would have expected as part of his own ancestry. How is it possible with my pure German descent to have a distant cousin with some grandparents from China?
This is a point worth to be focused – and illustrated.
There has been a famous son of my town Cologne in the 17th century – Johann Adam Schall von Bell, whom I would like to abuse as an example in an experiment of thoughts. He was a Jesuit missionary and succeeded in becoming a mandarin of the first class at the Chinese emperors court, named Tang Ruowang. The fundament for this career have been his skills in mathematics, astronomy and his knowledge in the cannonball construction. As a highly gifted young man of sixteen he decided in 1608 to leave Cologne and head for Rome to join the Collegium Germanicum, although the age of entrance was eighteen, but he could successfully convince them.
There are no spouses or love affairs reported, but let us pretend for our experiment, that he had at least two of them. We could imagine, that he left a young German girl pregnant behind in Cologne and later in China had an affair with a noble Chinese woman.

  

As a possible common ancestor we should have a look, what could become of his genome in two different geographical contexts.

   

Due to recombination his original genome will be reduced by halves in each generation, but we cannot know, which segments will completely vanish or rest conserved as tiny bits and pieces. In our Chinese simulation we can expect this reduction in the given ratio, as his German contribution functions like a drop in the ocean. After 12/13 generations it will be hard to trace German parts in his Chinese offsprings.

 

 If we draw the triangle comparing the genomes of Schall von Bells offsprings, we can perceive two phenomenons: at about the same ratio of proportions there should be a slightly different outcome, because recombination not occurs at the same breaking points. The second difference is the important one for me: in the Chinese genepool original segments will vanish regularly and rapidly, but in a regional German genepool there are repeated chances in the course of generations, that segments could accumulate and recombine over and over, thus creating segments, whose real age is unclear, but who should be considered as specific for geographical regions. But this has to be proved!  

http://de.wikipedia.org/wiki/Adam_Schall_von_Bell

Triangulation 1 ( Reflections )

My tyrolean cousin 

Each comparison generates its own visual form. Genetic ones don't need a spatial background like a measure scale, but something inevitable - time! And this form seems shaped to me like a ladder or a triangle. The most simple way of comparing works with mitochondria, since they are small, stable and mutate very slowly. One foot of that ladder now is defined by the revised full genome raw file of the Cambridge Reference Sequence, the rCRS. Before there has been a Yoruba sequence and others, since Anderson extracted the first sequence in 1981.
The third part of that triangle is the MRCA, the most recent common ancestor and depending on the amount of mutations he has to be placed further back in time.
Here is a first triangle, combining the rCRS with cousin clade - H11a2. The listed mutations correspond to the usual phylogenetic tree ( http://www.phylotree.org/ ). The faces belong to a series of drawings, tying various women of all parts of the world together in a vertical social network ( http://zaender.com/ur/magenta/marias.htm ) .

For a better understanding I laid the ladder aside, so the MRCA is now left hand instead of the top. But still each mutation – or better haplogroup – functions like a rung of a ladder.

I started to mistrust the former age estimations. H11 has been considered to be older than 40000 years, probably due to the fact, that each mutation on the Hyper Variable Region 1 was handled with a rate of 10000 years. In this clade you usually find four mutations, while most of the other about 40 subclades of haplogroup H can only be defined by a Coding Region mutation - ergo! The appearance of H11 in Siberia supported this time estimation.

The more mutations you find, the further back in time your last common ancestor must be considered. In the case of H11 you only have to go back until H, then turn aside on the branch of H11. To reach my own haplogroup K1b2a or that of my distant tyrolean cousin, the iceman from the Ötztal, we have to pass H and go back until R, about 60000 years, before we come to K via U and U8b.

Results:
http://zaender.com/ur/css/12chr.pdf

List of anonymised contributors
http://zaender.com/ur/css/regband.csv

Set of chromosome stylesheets
http://zaender.com/ur/css/css.pdf

First online version of a flagged european landscape
http://zaender.com/ur/css/cssmain.htm

Project description

Each new match in „Relative Finder“ opens up a line of possible connections towards a common recent ancestor somewhere back in 4, 7, 10 generations. RF was released by 23andme in autumn 2009, binding a small community of about 30000 genetoholics together in a facebook-like social network. Very few of them ended up to actually proof such a genetic connection in a traditional genealogical way, most are still full of hope. RF only encompasses half-identical regions (HIR’s) with a genetic distance value of greater than 7 centiMorgan and more than 700 single nucleotid polymorphisms (SNP’s).
Half a year later the users of 23andme could welcome an additional new tool – „Ancestry Finder“, listing also smaller matches between 5 and 7 centiMorgan and all the emigration-, coemigration and immigration countries, our grandfather generation comes from. The computer generated graphic design of AF is rather poor – the tiny chromosomes can only show one match on one spot, all additional clustering matches must stay hidden. And there is no scale!
I wanted to have a visual representation of a chromosome set, giving them an individual face with enough room for hundreds of matches. I therefore created a handle of stylesheet with columns for names, haplogroups and the number of SNP’s (URL).
Collecting ones matches in those stylesheets soon reveals, that most are not spread randomly along all chromosomes, but cluster together or are at least considerably overlapping, while a few others stay relatively isolated. Some of these clusters, especially those of lower cM values tend to start or end exactly at the same positions. Probably they are of a high age due to inversion or yet unknown geneprotecting reasons. Between single matches of perhaps individual interest and such of old pan-european background there are I expect clustering chromosome segments, recombined over and over, thus accumulating region specific pattern and shaping a possible european genetic landscape. This is actually not proven and may turn out to be just a phantom, but anyway a collection of clustering HIR’s should give a valuable background to judge ones matches. All postings around the Regional Ancestry Bands will be displayed in the form of Settings, Reflections and Results.