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
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tirsdag 19. april 2011
mandag 18. april 2011
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 |
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