Wednesday, November 22, 2006

Here's the skinny -

After several emails with John McEwan I now believe I mostly understand what he is trying to tell me.   Fortunately, he's a very patient man.

Apparently, because of the way FTDNA and others report multi-copy markers, what appear to be recLOH events may not really be.   They may, in fact, actually be deletions.   In order to be as nearly correct as possible, however, I should say that both are recombination events, one, called recLOH, a gene conversion where one copy is overwritten by the other copy, and the other actual gene deletions.

Fortunately, for most of us that won't make any difference because all we're interested in is being able to count genetic distances in order to determine relatedness and, again fortunately, both are treated the same for that purpose.

Some of you, however, may be interested to actually know whether your 'apparent' recLOH markers are really gene conversions or deletions and John has told us how to discover that.   I'm going to quote from several of John's emails to me and so that you will be able to easily tell when someone who knows what he's talking about is speaking, I'll put his quotes in green.

For starters, he changed the language slightly of the longer paragraph of the Wikipedia article I began our recLOH page with to better conform to his belief:

When Y chromosome STR databases are searched for twin alleles at 3 or more duplicated markers on the same palindrome (hairpin), e.g., DYS459, DYS464 and DYS724 (CDY) on palindrome P1, then a higher than expected proportion of 9-9, 15-15-17-17, 36-36 combinations and similar twin allelic patterns will be found.   PCR typing technologies and new markers have been developed (e.g. DYS464X and DYF399) that are able to distinguish that these results are a combination of gene conversion or RecLOH events and deletions caused by unequal recombination.   The true rates of both processes are not known, but for the P1/P2 palindrome where deletions and gene conversions can usually now be distinguished the deletions are more prevalent.   The frequency of these events has not been well estimated, but appears to be intermediate between the mutation rate of STRs (~1E-4) and SNPs (~1E-8).   However, the outcome is the same:  what appear to be 3 separate, often multi-step mutations in different markers is in fact one single event.   So a 9-10, 15-16-17-17, 36-38 haplotype can change in one recombination event to the one mentioned above, because all three markers (DYS459, DYS464 and DYS724) are affected by one and the same mutation.   Appropriate allowance for this must be made when comparing individuals at these markers.   Genetic distance calculations commonly used for single copy markers may not be appropriate.   -and I have likewise so amended our recLOH page.

Summarized, For the P1/P2 deletions it is simple, you test with the palindrome pack and the deletions as distinct from gene conversions will be obvious because of the results at DYF371, DYF385, DYF397, DYF399, DYS725 and DYF408 where there will be MISSING alleles.

. . . DYS385a,b can be I think sorted out using the Kittler test (it can sort the alleles) and I think these mostly are real RecLOH events.

We might need someone to help us interpret them, but all the tests mentioned, including DYS464X, are available from FTDNA through their Advanced Orders section in their Panel 5 Palindromic Pack and their Kittler panel.


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