Monday, November 13, 2006


Recombinational loss of heterozygosity has been a big topic of discussion on the DNA lists recently where folks are attempting to understand its effect on genetic distances as genetic distance is a measure of 'relatedness'.   I'm having a great deal of difficulty with not only the concept but also coming to an understanding of just what occurs during the recLOH process.   I've attempted to gather some materials so that perhaps some of you might be able to grasp the concept and explain it to the rest of us.

From Wikipedia:

"RecLOH is a term in genetics that is an abbreviation for "Recombinational Loss of Heterozygosity".

This is a type of mutation which occurs with DNA during recombination.   From a pair of equivalent ("homologous"), but slightly different genes, a pair of identical genes results.   In this case there is a reciprocal exchange of genetic code.

In genetic genealogy, the term is used particularly concerning similar seeming events in Y chromosome DNA.   This type of mutation happens within one chromosome, and does not involve a reciprocal transfer.   Rather, one homologous segment "writes over" the other.   The mechanism is presumed to be different from RecLOH events in autosomal chromosomes and probably like gene conversion, as it has been witnessed in bread mold.

During the mutation one of these copies overwrites the other.   Thus the differences between the two are lost.   Because differences are lost, heterozygosity is lost.

Recombination on the Y chromosome does not only take place during meiosis, but virtually at every mitosis when the Y chromosome condenses.   Recombination frequency even exceeds the frame shift mutation frequency (slipped strand mispairing) of (average fast) Y-STRs, however many recombination products may lead to infertile germ cells and "daughter out".

Recombination events (RecLOH) can be observed if YSTR databases are searched for twin alleles at 3 or more duplicated markers on the same palindrome (hairpin).   E.g. DYS459, DYS464 and DYS724 (CDY) are located on the same palindrome P1.   A high proportion of 9-9, 15-15-17-17, 36-36 combinations and similar twin allelic patterns will be found.   PCR typing technologies have been developed (e.g. DYS464X) that are able to verify that there are most frequently really two alleles of each, so we can be sure that there is no gene deletion.    Family genealogies have proven many times, that parallel changes on all markers located on the same palindrome are frequently observed and the result of those changes are always twin alleles.   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 recLOH event."

The ISOGG glossary explains recLOH as "When a section of DNA on a marker is missing, that marker is sometimes repaired by another marker filling in the missing DNA with its own material.   This is referred to as a "recLOH event" and is usually observed with multi-copy markers like 385a and 385b, and is also common in the 464 set.   The recLOH event causes the allele values to match 11-11 instead of the more common, 11-14 that you see in R1b."

A discussion of DYS464 by John McEwan that touches on recLOH.

Here's Thomas Krahn's explanation.

Thomas' diagrams...

Below from Adrian Williams from yesterday's DNA list...


I have been able to talk with Bennett a few times this week and he helped clear the air (and my head).   Hopefully this will clarify the information and measuring genetic distance on the palindromic markers.

Yes, measuring the recLOH is with each palindromic arm.   For example, DYS385 is on P4 while DYS459, DYS464 and CDY (DYS724) are on P1 and YCAii is on P5.    From the information from the conference that ALL lettered markers are affected (i.e. suffixed with a letter a, b, c, etc).

And you are also correct that the recLOH is very other words, according to Bennett, the numbers will be identical in a recLOH event.   For example, on 385 a person with  11  11  and another with  11  14.   A recLOH has most likely occurred here with the  11  14  being the ancestral value and the  11  11  being the newly recombined value, the genetic distance being  1.    And, when I asked about a non-identical move, for example two CDY values:  37  38  and  37  39,  these do not constitute an recLOH event and is simply a mutation.

Additionally, both Bennett and Thomas indicate that all mismatches on a given palindromic arm that are caused by a recLOH are counted as one.

So, this is my understanding of the way we count the mismatches on palindromic markers:

Given these results (from Thomas' presentation at the conference) of markers that all occur on the same palindromic arm:

DYS459 DYS724 (CDY) DYS464 Genetic Distance
9-10 37-38 14-14-16-18 MODAL
9-10 37-38 14-15-16-18 1
9-10 37-38 14-14-16-18 0
9-10 37-39 14-14-16-18 1
9-10 37-38 14-14-16-18 0
10-10 38-38 14-14-18-18 1
9-10 37-38 14-16-18-18 1

In this example, Thomas has clearly indicated that a multi-marker recLOH on that same palindromic arm constitutes a 1-step mutation.   So, instead of the last results set being 3 steps from the modal, it is only 1, the mindset being that the repair event occurred along all portions of that particular palindromic arm.

And you can very well have an event on one arm and not the others, which makes our mismatch determinations even more fun!

Now, using the same set and adding the other palindromic markers, you can see, each arm is counted independently.

DYS459 DYS724 (CDY) DYS464 DYS385 DYSYCA Genetic Distance
9-10 37-38 14-14-16-18 11-14 19-23 MODAL
9-10 37-38 14-15-16-18 11-14 19-19 2
9-10 37-38 14-14-16-18 11-11 19-19 2
9-10 37-39 14-14-16-18 11-14 19-23 1
9-10 37-38 14-14-16-18 11-11 19-23 1
10-10 38-38 14-14-18-18 11-11 19-19 3
9-10 37-38 14-16-18-18 11-11 19-19 3

I hope this clears my earlier confusion.   There is some additional information about DYS464 and how it can exist on two different arms, but that is another discussion for another day.   If someone can help clarify and/or correct this, I know I for one will be grateful as I was still in the "oh crap!" mindset when some of this was being explained during Thomas' presentation.

Kind regards,

With this addition from Vincent Vizachero...

I would only add the following, based on my recollection and understanding:

1. There are two possible configurations of P1 and P2.   They can exist separately or combine into a single palindrome arm (P1/P2), thereby raising the number of possible solutions.

2. Palindromic regions do not always manifest as palindromic arms, which is one reason that sometimes you can get a RecLOH and sometimes just normal mutations.

3. The parsimony principle dictates that you establish the minimal number of steps that can explain your results.   For example a mutation at DYS385 from 11,15 to 11,12 should be counted as a GD of 2, not 3.   The most parsimonious explanation is a RecLOH (the 15 became 11) followed by a normal mutation (one of the 11s became a 12).


If you think that you're really up for it, here's the link to Thomas Krahn's Presentation on palindromic markers at the recent FTDNA sponsored International DNA Genealogy Conference in Houston 2006, the basis for the bulk of this discussion.   Or, here's an alternate link.

Click here for lesson two.


Post a Comment

<< Home