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.

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.

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.

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

EUROPE ONLY

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.

SUMMARY EUROPE ONLY:

* 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.

EUROPE PLUS SIBERIANS:

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.

SUMMARY EUROPE WITH SIBERIANS

* 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.

Updated local Fennoscandia analysis

-- 3 new participanst: 2 from Sweden and 1 from Finland.
-- Changable 3D plot for D1-3 sendt to all participants by email.
-- Else nothing new to comment.

Have questions or want to participate? Send email to tjaaehkere at yahoo.no

A SMALL COMPARISMENT OF LAMP, ADMIXTURE AND AIMs

INTRODUCTION

The LAMP 2.5 genetic analysis software picks AIM's in its analysis based on the allele frequences given to it. On this basis I would like to check how LAMP perform by comparing to the widely used ADMIXTURE software. Of special interest are if ADMIXTURE clusters individuals similar to LAMP.

METHOD

I first estimatet the ancestral frequency data for Norwegians, Swedes, Saami and Finns from a subset of individuals clustering to these based on their MDS plots. I then run LAMP on recommended settings except this time I run it assuming the populations had been mixing for 10 generations the same presumption used in ADMIXTURE. I then picked the AIM's chosen for this analysis by LAMP and used them in a run for the whole dataset of 36 individuals.

OBSERVATIONS:

* All the Finns who clustered close to or 100% in LAMP also did the same in ADMIXTURE.

* In LAMP 9 Norwegians appeared 100% or close to 100% Norwegian. In ADMIXTURE 2 of these 9 appeared strongly mixed with Saami and Finns in ADMIXTURE.

* Saami all appear in LAMP close to or at 100% Saami. In ADMIXTURE only 1 appears as heavily mixed.

* All the Swedes who appeared as 100% Swedish in LAMP was also classified as 100% Swedish in ADMIXTURE.

* The Norwegian mixture in Swedes and Finns appears stronger in LAMP than in ADMIXTURE for those individuals who have it.

* Saami amix proportions seen in considerabe proportions in ADMIXTURE are often very little or gone in LAMP.

COMMENT:

It seems LAMP and ADMIXTURE is largely consistent about the "pure breed" and supports that the ancestral allele frequency data used in LAMP are correct. What LAMP and ADMIXTURE do disagree some about are the admixtures. 3 individuals who in ADMIXTURE was classified as mixed was not or very little admixted in LAMP. The reason for this are that LAMP and ADMIXTURE uses different methods to estimate admixture.

ADMIXTURE basically estimate allele freqency differences between SNP that is assumed to be independent and than cluster it. It does not care about physical positions of SNP, cM (centimorgans) between SNP and recombination events as far as I can tell.

LAMP however first picks AIMs (ancestry informmative markers) and goes trough the whole chromosome piece by piece in a moving window that changes in size depending on the physical position and the recombination rate of the window where it constantly compares to the given ancestral alleles for different populations. In this it differ from ADMIXTURE by looking at a group of SNP instead of a single SNP as ADMIXTURE. It comes without saying that comparing a group SNP gives a higher likelyhood of differentiating the actual origin of a segment than a single SNP.

This likely explain why some individuals that showed considerable admixture in ADMIXTURE had little or no such admixture in LAMP and why some proportions of other admixtures seen in ADMIXTURE was gone in LAMP. If looking only at single SNP's and averaging them some people may have f.ex "Saami" looking allele frequencies spread over the chromosome but when checked vs a segment of SNP's in the same segment they where actually more likely not of Saami origin.

In ADMIXTURE such problems as mention above go unnoticed unless the admixture is real and you can actually observe by comparing ADMIXTURE vs LAMP results that where the results appear consistent in both analysis its probably real or at least consistent given the parameters and data. This is because if the admixture is real a considerable of number of single SNP's with frequency close to a source populations will be there and it will of course by detected by ADMIXTURE.

Anders

I had earlier problems discriminating norwegians and swedes using the MDS plots and the ADMIXTURE program. This is have been problem that needed to be solved. I have for that reason (and some other reasons) learned a new genetic software called LAMP 2.5.   This program have been specially designed to seperate individuals from closely related populations and it is able to specify what segment of the chromosome came from which population. The end result is quite similar to what is offered by 23andme's Ancestry Painting but instead of showing the dull labels "European", "African" and "East-Asian" you instead will see "Norwegian", "Swede", "Finn/Suomi" and "Saami" labels on your chromosome. In this test run I have limited the analysis to the X-chromosome but the analysis shouldnt be problem to escalate to the rest of the chromosome and to include more distant surrounding populations to investigate the relationship to continental Europe. The program may also be useful to detect specific segments for mixed dispora populations. The X-chromosome is a sex chromosome. It never pass two male generations. If you are a male you get your X-chromosome from your mother. If your female you get your fathers X-chromosome and one of the two of your mothers X-chromosome. If you are a male and have a Swedish mother and a Finnic father you would in a autosomal DNA analysis look like a 50/50 Swede/Finn but your X-chromosome you would appear as 100% Swedish because as a male you get your X-chromosome only from your mother. Whats do the analysis show? 1 The program is suprisingly good to label the main ancestry for each participants: a) All Norwegian participants where placed in correct category including two persons with large Saami and some Finnic mixture. b) Most Swedes participants where placed in correct category but 5 Swedes appeared to look more genetically similar to Norwegians than Swedes. This was also the case for a Swedish Finn (even a Estonian) who appeared to look more similar to Norwegians than to Swedes. Also worth to note that these Norwegian looking Swedes had some Finnic and even Saami admixture other Swedes didnt have. It may suggest that these participants have ancestry from the northern parts of Sweden. c) The Finns also have a good fit but there are some exceptions like the Swedish Finn mentioned above. This Finnic "outlieers" appears to come from border sones with other populations. d) The Saami appears to cluster nicely togheter. There appears to be some variation for one individual when assuming less time since the admixture event begun. There doesnt seem to have been more geneflow from scandinavians than finns or viceversa to the Saami. The most intriging question that arise from the above analysis are why do some swedes appears as more Norwegian than Swedish togheter with some Finnic and even Saami admixture in other words political borders do not seem to match the genetical borders completly. The traces of Finnic and Saami from this individuals suggest it is a northern phenomena in Sweden maybe from earlier migrations but it doesnt explain why a Swedish Finn and even a Estonian get so huge "Norwegian" percentages. Whats next? * More LAMP analyses trying to track origins to continental Europe * IBD analysis using newest technology. This will involve phasing of the genome for all participants. All will get their phased haplotypes for their chromosomes if they want. * ADMIXTURE analysis * MDS plots Anders