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The science behind Big Y 700 mutation rates

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  • #16
    Originally posted by benowicz View Post

    . . .1. I manually calculated the ancestral modal haplotype. It seems to me clear that the programming logic for those calculators is pretty crude and either not appropriate generally or at least not appropriate for the specific cases that I encountered in my analyses. For example, I think there is a much better case for assuming the ancestral modal value in ambiguous cases where there is, strictly speaking, no mathematical modal, to be the median allele count rather than the lowest allele count. . . .
    Forgot to mention that a corollary of this is my opinion is that it's not reasonable to apply either the step-wise or infinite allele method universally across the board for all markers when calculating TMRCA. So I basically had to perform this manually, outside of the standardized, automated calculators I found online. From what I can tell, nobody ever claimed that multi-step mutations were more than a small minority of total mutation events--maybe less than 10%, although they do appear to occur more frequently on multi-copy markers. This is a pretty important point.

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    • #17
      Originally posted by benowicz View Post
      . . . The end results of my revisions are not too different--I figure the estimated birth year of the MRCA for FGC23343 at the 50% confidence level was about 718 A.D. But I had to make a few judgments and manual adjustments . . .

      3. I think it's possible to revise downward any rate adjustments due to the likelihood of convergent mutations by analyzing more than 2 donor haplotypes. My independent attempts to calculate these adjustments and compare them to the adjusted rates used by several other popular TMRCA calculators came pretty close--typically within 3% of the rates implied by those calculators' results. I consider those differences to be insignificant, and currently think they're due to some highly dubious algorithms weighting the impact of specific loci. Anyhow, confident that I can reasonably approximate the expected impact of convergent mutations for any observed genetic distance, it follows that the probability of those convergent mutations with respect to the constructed ancestral modal haplotype decreases proportionately to the number of independent donor haplotypes examined. . .
      Upon further reflection, I think the downward adjustment reflected in that original calculation was too high. The theory is that each additional haplotype analyzed should reduce the chance that any convergent mutations would affect the reconstructed ancestral modal haplotype, and that can only happen if there are at least 4 haplotypes being analyzed, since by definition convergent mutations appear in matching pairs.

      Unfortunately, there aren't enough independent donor haplotypes available to do this at any level other than the parent level of this subclade, FGC23343. Anyhow, now examining 5 rather than 3 haplotypes, I have to revise backward the estimated birth year at the 50% confidence level for the MRCA to 636 A.D., about 2 or 3 generations earlier than my last estimate. That's just slightly closer to the estimated value under the SNP analysis using what I call the Xue rates (i.e., 876 A.D.), vs. the Adamov rates (i.e., 333 A.D.).

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