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tirsdag 29. november 2011

Geographic MDS maps of Fennoscandia and Europe (updated)

There exists some similarity between Finns and Lithuanians not seen in Saamis, so when adding the Lithuanians the Finns moved out of the North-Saami cluster compared to the previous analysis. Therefore Lithuanians where added. Also FI5 and FI6 where 2nd cousins pulled down the Finns into the North-Saami cluster. Removing each indepentently resulted in the same effect suggesting the relatedness had an effect in the analysis. FI6 was therefore removed.

The MDS plots can be confusing for some. I therefore made a map showing the geographic average distributions for the 3 main components and it may show an intriging history. Dimension 1 accounts for the most of the variation, while dimension 2 account for the second largest genetic variantion while dimension 3 account for the third largest genetic variation. Therefore the dimensions do not acount equally when represented in a 3D view.

The map appears to show Saamis as extremes in all three dimensions.

This is how much each dimension explains the genetic variation in each dimension:

 D1: 20 604 SNP 4.2%
 D2: 10 417 SNP 2.1%
 D3: 8 560 SNP 1.8%
Dimension Total: 8.1%

D1: Saamis, Finns and Vologda Russians appears to make a far eastern bridge. Earlier analysis seem to suggest that this is a Siberian component seen in Europe. It appears absolutely lowest among the Italians. Note that the Italians appears to be "isolated" in Europe in this context with much higher rates seen in close populations. Scandinavians appear closest to Belorussians and Hungarians in this dimension.

D2 also appears very high among the Saami and seem to have a western European distribution as it has high frequency also among Finns, Swedes and Norwegians. It is also higher in western Europe as seen among the French and Italians. However it drops very dramatically from Finns to Lithuanians, Estonia and Vologda Russian. The level increases again in more western east-European populations like Hungarians and Romanians.

D3 also appears very high among the Saami but shows an intriguing pattern. Its very low among Scandinavians, Lithuanians and Estonians, however the next highest occurrences are found among the Italians, then the Romanians and the Vologda Russians and then finally Finns just somewhat above intermediate levels like the French, Hungarians and Belorussians. 

May it be the "eastern component" researcher Tambets mentions in her abstract for the coming paper about genetic of the uralic speakers? If yes why is it also found second highest among Italians?

Also the local opposite clustering of this component only seen among Norwegians, Swedes, Lithuanians and Estonians are intriguing suggesting something in common.

As the result indicate the Saami outlierness appears to be the sum of these 3 different dimensions or genetic components. Italians appears to be opposite outlier in D1, Lithuanians appears to be opposite outlier in D2 and Swedes appears to be opposite outlier in D3.

fredag 25. november 2011

Fennoscandia BGA regional MDS update (2nd update)

We got 5 new project members since last update. SWE17, SWE18, SWE19. FI12 and FI13. The interpretations are much the same as given in earlier posts. We can see that SWE14 and SWE17 are outside the main Scandinavian cluster pulling toward the eastern European populations. SWE19 appears to cluster well into the Scandinavain cluster. Interesting that FI12 a southern Finn appears close to the Estonian ES1 halfway towards the Vologda Russians and the Belorussians. FI13 have ancestry from Savo and cluster in the Karelian cluster.  

We also see some slight movements of others after adding more individuals. This is normal as adding more individuals influence the positioning of all other individuals especially the closer ones to new added individuals.

tirsdag 22. november 2011

Fennoscandian Mutation Sharing Matrix

All participants have received the Mutation Sharing Matrix of currently known unique haplotype mutations map for Fennoscandia shared with two or more individuals. These mutations is currently only known in Fennoscandia.

Its highly recommended to use Excel 2007 or later when using. Enclosed Excel 2007 and Excel 2003 versions.

X-axis - Individuals
Y-axis - Clusters

How to use:

1. Find your code at the top.
2. Hit the filter and choose "1".
3. You now have a overview over at what cluster and to what other individuals you share mutations with.
4. To the far right is a indicative distribution of the cluster etnical distribution. Please use with extreme caution in regards to interpretation.

Other things:

* Individuals of known partly Saami ancestry is indicated with blue colour.
* Individuals of known partly Saami ancestry is labeled as Norwegians and Swedes.
* Interpretation of mutation patterns must be done with extreme caution. There are many possible problems like etnical categorisations for haplotypes that is also shared outside ethical boundaries but within geographical boundaries. The mutation could be "native" but also arrived trough later migration.
* Widespread distributions may indicate higher age for the mutation cluster or it may indicate a common immigrant who hit the genetic jackpot.

If you have not received the sheets please contact me on email.


mandag 21. november 2011

Accurate method for pinpointing autosomal ancestry?

In the earlier post I reported to have found 2 haplotype clusters seen in 6 individuals each. I here look closer at 1 of those 2 clusters to see what can be inferred from them.

The core haplotype

The haplotype identified occured in 6 individuals: 3 Finns, 2 Swedes and 1 Norwegian (no Saamis) and no one else in the population panel. The core of the haplotype is GC with the markers rs6683734 and rs4649296. These are together mutations that can only be found among Fennoscandians. However the spread is very limited only occuring in 6 of 88 haplotypes (or "3" of 44 individuals).

The extented haplotype

The haplotype can be furter extended for all with these markers: rs16858853 rs12087818 rs701177 rs16858884 rs701176 rs701173 rs11800619 rs10489806 rs7546115 rs10910120 rs1033322 rs12124323 rs17752790 rs6697791 rs12140862 rs12130755 rs6683734 rs4649296. The physical distance between the first and last is 75kb or 0.075 Mb. The individual haplotype appears to have gone trough recombination if extending the haplotype further.

The extended haplotypes founder haplotype appears to have accumulated several mutations that appears to have some local variation suggest it has a age and history in Fennoscandia seen in total. Two Finns FI11 and FI12 appears to share what appears to be the founder haplotype. FI10 have accumulated two mutations not seen in anywhere else. The SWE1 and SWE13 haplotypes appears to have separate history from the founderhaplotype seen in the two Finns. Here the SWE1 appears to be the founder while the SWE13 appears as a subfounder. The one Norwegian haplotype NO5 appears to have a history closest to the Finn haplotype.

The mutation diversity suggest a history even its widespread. The founder haplotype is seen in Finland while 4 of 6 mutations is seen in Swedes and a Norwegian. The Swedes even have a sub-node haplotype. This suggest that Sweden is the oldest location for this haplotype with Finland as runner up. It may be youngest in Norway but belong to the Scandinavian cluster in other analysis so it may be grouped with Swedes. More samples could possibly enlight the question of origin.

The ancestral haplotype

It would be of great interest to identify the true ancestral haplotype to the above described haplotype in Continental-Europe to be able to infer the "point" of entry to Fennoscandia.

I managed to extract this possible ancestral haplotypes. Two from Spain and 1 from the French Basque. As seen from these it appears like third last and last SNP mutated in Fennoscandia from AGA to GGC. The Norwegian's AGC may be due to back mutations, error or it could be transition between the third last and and last SNP. If correct this could mean the point of entry was Norway but it is inconsistent with extended haplotype having the lowest diversity but not if we group Swedes and Norwegians.

The SNP before the last tree is the common founder haplotype. I attempted to find sign of diversity for the Iberians for this part but didnt manage to detect any at first screening. The zero diversity of the Iberian group for this part compared to the Fennoscandian suggest the Fennoscandian haplotype are older. The difference is mutated positions for the third last and last SNP.

SUMMARY:  As seen from this posting trying to reconstruct a autosomal haplotype could be complex but give accurate and informative genetic history. The core haplotype appears to be simple and effective in proving Fennoscandinavian ancestry despite its tiny size, while the extended haplotype can provide clues to its age and history.

This method using core haplotypes with limited distributed mutations appears to be very accurate in pinpointing ancestry

fredag 18. november 2011

Autosomal Haplotype Clustering Patterns - Actual or Error? (updated)

I have found this pattern of haplotype clustering within individuals from Norway, Sweden and Finland on Chr 1 using 38.5k SNP:

Unique haplotypes not shared with others - 1 344 (typical between 15 to 50 per individual)
Haplotypes shared between 2 ind - 157
Haplotypes shared between 3 ind - 30
Haplotypes shared between 4 ind - 3
Haplotypes shared between 5 ind - 2
Haplotypes shared between 6 ind - 2

As this shows widespread haplotype clusters are much rarer than those shared with only two individuals, but the "unique" haplotype clusters appears to be absolutely highest at the individual level.

This raises the questions why its like this. I suspect its the following reasons:

1. The effect of recombination splitting or killing haplotypes. However the maximum haplotype size in clusters is 500 SNP. Redusing it to 100 SNP only reduced to 1324 unique haplotype clusters. Reducing to max 10 SNP only reduced to 1189 unique haplotype clusters. Reducing to 5 SNP reduced only to 962 unique haplotype clusters. If reducing to 2 SNP only 277 unique haplotype clusters.
2. The effect of limited population data. Its possible more individuals and populations would reduce the number of unique haplotype clusters.
3. The effect of undetected errors in the genotypes. However no correlation between high unique haplotypes found in individuals and high detected genotype error rate for these.
4. The effect of incorrect phasing as the result of errors in genotype or/and ordinary phasing error as result of the model used.
5. The effect of haplotype or mutation extinction. Recent individual haplotypes or mutations have limited spread generally, while older haplotype clusters or mutations have larger geographic spread.

So what I infer from this is that these unique haplotype clusters is rather small and not very large. These numbers have been generated from software made for finding genetic diseases from haplotypes where you mark individuals with certain traits cases and check them vs the controls. If there is any haplotype strongly associated with a trait the associated haplotype is found. These haplotypes are usually not very large. Just check the SNP used by 23andme health section.. So is also the cases with these haplotypes.

The software do for many haplotypes infer parent-child relationships between them indicating that haplotype mutations are in the picture at least when I check at the individual level.

mandag 7. november 2011

How genetic similar or disimar where your parents ancestry? (updated)

How genetic similar or dissimilar your mother and father ancestry is of some interest in infering your past genetic history. In scientific language its called "Runs of homozygosity" or simply "ROH" and are segments of identical blocks of DNA on your autosomes that you received from both of your parents.

In one hypothetical extreme if your parents where closely related like cousins you would have a few large segments of ROH or if both came from the same population isolate or village but not recently related, many small ROH segments. On the other side if your parents where of very different origin  you would probably have very few and short ROH segments. In fact ROH works similar to 23andme's Relative Finder by finding common segments between your parents. If sharing many segments, probably related, if sharing few or no segment not related.

ROH therefore provides insight on whether your ancestors derived from a small isolated population, were of mixed or urban origins, or even if there was consanguinity in your lineage.

I have attempted to reconstruct a similar analysis provided by Etnoancestry using PLINK's ROH functionality. I used the following parameters (default settings):

Min ROH size: 1 Mb
Min ROH SNP: 100
Min ROH Density: Kb/SNP: 50
Largest ROH Gap: 1 Mb
Number of SNP: 530k, 22 autosomes, no pruning.

The ROH run for each participant is presented in the graph below. As shown there appears to be great variation between the samples. The Y-axis represent the number of ROH segments found while the X-axis represent the sum size in Mb for all those found ROH's. In the one extreme FI10 and SWE16 is found to have the largest  number of ROH's and the largest total size of ROH or in other words they had parents with the most similar ancestry. On the other extreme you find NO7 and NO11 both of mixed backgrounds, the first Norwegian-Saami mix and the second Norwegian-Swedish mix (and possibly some minor Saami/Finnic mix), in other words they had the parents with the most dissimilar ancestry.

So then the question naturally of course arise, do these individuals with high ROH is the result of recent inbreeding or consanguinity? The answer can be infered by calculating the average segment size by dividing the total size of ROH with the number of ROH found. If the calculation result in a few large segments its indication of recent consanguinity as few recombination events have divided the ROH into smaller pieces since the consanguinity, however if the calculation result in many number of small ROH its an indication that your came from a small population isolate with little consanguinity in recent times as recombination have split the ROH segments into many smaller pieces.

The calculation of the average ROH block size among all members appears consistent with a scenario with no recent consanguinity for all participants (visually confirmed with actual data). To illustrate it SA2 who score very high in both number and sum of ROH but the average ROH size isnt so much different from NO7 who's have the least similar ROH.

In MDS plots having a individual with extreme ROH would have similar effects like having related samples resulting in own clustering. In 23andme's Relative Finder individuals of from same population isolate would appear artificially as closer relatives than they actually where.

fredag 4. november 2011

Investigating the genetic background of Finns

We continue the analysis of the latest MDS run now looking at the Finns. In the plot it appears that Finns divide into several groups with different origins.

The first group is the Karelian group. These are individuals with most of their background from from Finnish Karelia. FI10 is entirely North-Karelian. This cluster appear to have somewhat lower Siberian influence than the Saami but with more similarites with Vologda Russians than other Finns as they appear to pull in the direction from the North-Saami and below mentioned Finns. FI2 who is outside this cluster pull even more towards the Vologda Russian cluster.

The second group is a more mixed group with ancestry from Tornea river area, Oulu, Lappi, Finnsih Karelia, Central-Bothna, NW, SW and Central Finland. FI5 who have ancestry from Western Finland pull slightly toward the Scandinavian cluster. The proximity of this cluster to the North-Saami in D2 is interesting it could mean Saamis have a close common background with this cluster in this dimension. However in D3 (not shown) this affiliation disappear. Else these Finns appear to pull slightly towards both Scandianvians (especially FI5) while FI3 and FI6 pull towards the Karelians and The Vologda Russians. Interestingly in linguistic research the Saami self designation is suggested to be come from the Häme (Tavastia) region in West/Central-Finland.

The third group is F4 and FI9 who appear together to form a Bothnian cluster. Both have most or all of their background from this area. This group appear to be intermediate between the second Finnish group and the Scandinavian cluster. NO6 position here is the result of this individual beeing a mixture of Scandinavian and North-Saami and so is only artificially in this cluster, as in D3 this affiliation vanish while FI4 and FI9 stays put to each other in D3 (not shown) between the second Finnish group and Scandinavian. FI9 appears to pull more towards the Swedes while FI4 appears to point towards the "other end" of the Scandinavian cluster.

The fourth group is F1 who is the only known Swedish Finn in this project. This individual is between the Scandinavian and the Bothian Finnish group and appears to point further at the second Finnish group. In D3 this individual appears to pull strongly towards the Swedes in the Scandinavian cluster.

SUMMARY: So to conclude it appears that Finns have both common and different origins. Finns appear in these dimensions to divide into two groups. All Finns appears to have something in common with the Saami in D2 however western Finns and Eastern Finns have different external influences. Western Finns appear to be more influenced by Scandinavians while eastern Finns appears more influenced by the Vologda Russians.

torsdag 3. november 2011

Finding South-Saami ancestry in Scandinavians

It appears that the local analysis been done so far had weaknesses. It appears not managed to catch all people of at least partly South-Saami ancestry. I suspect the reason have been in the MDS program itself with different sample sizes in clusters and numbers of clusters affecting the result especially for partly mixed individuals. When including more outside populations it appears to make genetic distinctions clearer within Fennoscandia possibly from the earlier mentioned reasons.

Ref pop: French, Italians, Hungarians, Romanians, Vologda Russians, Norwegians, Swedes, Finns and Saami.
Number of SNP: 530k (not pruned) - 22 autosomal chromosomes.
PLINK MDS plot dimensions: 3

In the earlier local analysis it appeared obviously that samples NO6, NO7 and SWE7 must have been at least of partly Saami background with especially SWE7 plotting "weird", but not as obvious for sample SWE11 who earlier in the local analysis showed some weak pull out of the Scandinavian cluster. In this newest MDS run however SWE11 seperated very clearly from the Scandinavian cluster together with unrelated NO6 and SWE7.

Lets look first at the new MDS plot. In this plot top-bottom axis appears to be east and west geneticially speaking with the Vologda Russians and Belorussians at the top edge representing the most eastern population and Saamis at first glance the most "western" population with following Finns, Scandinavians and French.

Lets look at the second dimension in the left-right axis. This appears to reflect Siberian influence in Europe. The Saamis and many Finns appears to have the strongest influence from Siberia with Vologda Russians, Belorussians and Scandinavians following. The lowest Siberian influence appears to be among the Italians, French and Romanians.

So what differentiate North-Saami from South-Saami? It can be shown in the plot below. In Dimension 2 (D2) where the North-Saami and South Saami cleary is alone at the lower part of the plot in the extreme "West". Obviously both Saami group share ancestry in this common European dimension. This picture however change when we compare to Dimension 1 (D1) that shows levels of Siberian ancestry. Here the North-Saami peaks together with eastern Finns to the far right, while the South-Saami have levels comparable to Swedish Finns.

About the South Saami samples: SWE7 is confirmed at least partly of Saami background but not of North Saami background. SWE11 have also some geneological confirmed minor Saami background and have most of the origin from current and earlier known non-North-Saami areas. No information is known about NO7.

As comparisment NO6 who have geogaphical origin in the North-Saami area seperate very clearly from NO7, SWE7 and SWE11 by pulling straight at the North-Saami cluster (SA1-SA4) and appearing immediate between the Scandinavain and North-Saami cluster demonstrating that the Saami origin is different for NO7, SWE7 and SWE11.

So apparantly SWE7, SWE11 and NO7 have South-Saami background.

onsdag 2. november 2011

Little Study of the Saami, Finns and Scandinavians

As large sample sizes have a tendency to drown the 4 sample Saami clustering I have done a small study using only 4 individuals from each population to try to infer the Saamis relationship with other populations. Only 12 of the 41 participants is included in this analysis but its interferance should apply to the rest in general depending on your clustering in the earlier posten local plots using only Norwegians, Swedes, Finns and Saami.

What have been used:

Ref pop: French, Italians, Hungarians, Romanians, Vologda Russians, Chuvash, Norwegians, Swedes, Finns and Saami. Siberians: Ngan, Dolgans. 4 samples from each cluster.
Number of SNP: 530k (not pruned) - 22 autosomal chromosomes.
PLINK MDS plot dimensions: 3


Dimension plot D1-2:

1. D1: This dimension on the right-left axis may reflect possible Siberian ancestry levels among the populations. Two Saamis reach the same level as the two of the Chuvashes. Finns follows close after together with two Vologda Russians. To the far left we find Italians who are most geographical distant appears to have the least of this influence. See also Europe plus Siberian plot including four unadmixted Siberians.

2. D2: This dimension on the top-bottom axis may reflect extremes between the Saami and Finns on the top and the Chuvashes at the bottom and where contintal europeans and Scandinavians appear as intermediate but closer to Saamis and Finns. Saamis and Finns are at the same level in this dimension suggesting a common background in this dimension while central-europeans share considerable more with the Chuvashes maybe from eastern influences that didnt reach the Saamis and Finns to the same extent.

Dimension plot D2-3:

3. D2: The top-bottom axis is the same as in D2 so the comment there is the same here.

4. D3: This right-left dimension appears to divide the Saami and the Finns. Here the Saami share the far right with 1 French and 2 Italians and 1 Romanians as a close follow up in what appears at first as the western or central part of a continental european cluster. The Finns appears on the left side of the continental cluster that appears as the eastern part of a continental europeal cluster together with Vologda Russians and Scandinavians. This suggest that Finns and Scandiavians have a more eastern origin than the Saami in this dimension who appears far western.


* Saami at first glance appears to have the largest "Siberian" ancestry followed by Finns and then Vologda Russians. Scandianvians appears at the same level as central-europeans. (D1)
* Saami and Finns appears to share ancestry. Scandianvians and Continental Europeans and Scandinavians appears to have more eastern influences pulling them closer to the Chuvashes. (D2)
* Saami have what appears at first to be a western component pulling them far "west" than both Finns and Scandinavians who appears as far "east" as Vologda Russians. (D3).

-> This analysis may suggest that part of the "West" origin of the Saami do not have its root in recent Scandianvian admixture.


Dimension plot D1-2:

1. D1: This dimension on the left-right axis appears to be between Siberians to the far left and europeans to the far right. The Saami pull to the left the most after the Chuvash then followed equally Finns and Vologda Russians. Scandinavians appears to stay the same as continental-europeans in this respect see comment D1 in the EUROPE ONLY analysis.

2. D2: This dimension on the top-bottom axis appears to be with the Saami in the one extreme and the Italians at the bottom. Finns follows the Saami just after. The Vologda Russians and the Chuvash fills the void between the Saami and Finns vs the Scandinavians who appears to be at the "northernmost" part of the long continental european cluster. The Vologda Russian cluster appears to bridge to the Finns. Siberians appears here to have something in common with central-europeans maybe admixture however in ADMIXTURE runs the selected 4 Siberians do not appear to have european admixture.
Dimension plot D2-3:

3. D2: Same as D2 in Dimension plot D2.

4. D3: The left-right axis appears to be a east and west axis placing Chuvashes to the far left. Finns appear a little more to the left than the Saami. Scandinavians appears to pull even more to the left togheter with what appears to be central european cluster. Vologda Russians appears imidate between Chuvashes and Central-Europe.


* Saami at first glance appears to have the largest "Siberian" ancestry followed by Finns and then Vologda Russians. Scandianvians appears at the same level as central-europeans (D1):
* Saami appears far west in D3 while Finns and especially Scandinavians cluster with central-Europe.
* Saami appears uppermost or norternmost in the D2 plot followed by Finns, Vologda Russians/Chuvash and Scandinavians, then central-europeans and southern Europeans at the bottom.