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Recombinational loss of heterozygosity -- an attempt to explain its effect on genetic distances as genetic distance is a measure of 'relatedness'.

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".                                         *   *   *   end of wikipedia quote   *   *   *

continuing, from John McEwan -
"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."

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, Adrian

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).


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.

It seems to me that we have two questions here:  One, how to recognize and count a recLOH event and, two, how to count multi-copy marker differences, whether a part of a recLOH event or not.

We are told that recLOH events must occur within a palindromic arm.   So what's a palindrome?

From Wikipedia - "In most genomes or sets of genetic instructions, palindromic motifs are found.   However, the meaning of palindrome in the context of genetics is slightly different to the definition used for words and sentences.    Since the DNA is formed by two paired strands of nucleotides, and the nucleotides always pair in the same way (Adenine (A) with Thymine (T), Cytosine (C) with Guanine (G)), a (single-stranded) sequence of DNA is said to be a palindrome if it is equal to its complementary sequence read backwards.   For example, the sequence ACCTAGGT is palindromic because its complement is TGGATCCA, which is equal to the original sequence in reverse."

"A palindromic DNA sequence can form a hairpin. Palindromic motifs are made by the order of the nucleotides that specify the complex chemicals (proteins) which, as a result of those genetic instructions, the cell is to produce.  . . . .   Recently a research genome sequencing project discovered that many of the bases on the Y chromosome are arranged as palindromes."                                        *   *   *   end of wikipedia quote   *   *   *

As illustrated by Thomas Krahn's diagram-
"A palindrome structure allows the Y chromosome to repair itself by bending over at the middle if one side is damaged."

My understanding is that this repair is the 'recLOH event'.   How then do we recognize it?

Recall from our previous discussion that our multi-copy markers (at least the only ones I know about) are DYS459, DYS464 and DYS724 (CDY) located on palindrome P1, DYS385 on palindrome P4 and YCAii on palindrome P5, and that within any of those palindromic arms the marker numbers "will be identical in a recLOH event"?   So look for duplicated markers in those mentioned.   For example,  9-9,  15-15-17-17,  36-36  for DYS459, DYS464 and DYS724, respectively.   That would indicate one recLOH event and, no matter what their values were before, a distance count of only 1.

Using Adrian's example, again which I've now modified -
the circles represent mutations and the oblong circles represent recLOH events.

However, assume we're starting with a   9-10,  15-16-17-17,  36-38  haplotype.   A 9-10,  15-15-17-17,  36-38 haplotype would not be a recLOH event, nor would a  10-10,  15-16-17-17,  36-38  haplotype nor a  9-10,  15-16-17-17,  36-36   haplotype, and, except for multi-copy marker counting peculiarities which we will consider later, would be counted in the usual manner.   We should be suspicious, however, of e.g., a  10-10,  15-16-17-17,  36-36  haplotype which, by the principle of Occam's razor would be a distance of  2, i.e., a recLOH event followed by a simple mutation.

At least, that's my understanding of it.

We will now consider how to count multi-copy marker differences not a part of a recLOH event.

The Non-recLOH Event Multi-copy Marker Distance Counting Protocol

We have just considered recLOH events in which the multi-copy markers on a palindromic arm can all change significantly and only result in a genetic distance of one.   Pending authoritative directions otherwise I have determined how I will advise the members of this surname project to count genetic distances for differences in multi-copy markers that are not part of a recLOH event.   Multi-copy markers are those markers that have a small letter of the alphabet associated with them, i.e., DYS385a & b, DYS459a & b, DYS464a,b,c & d, CDYa & b, and YCAiia & b.

Consider that each of these markers is made up of two or more 'parts', each part represented by a value, e.g., DYS385a is 11 and DYS385b is 14, so we will designate DYS385 as 11-14, the two 'parts' being 11 and 14.   If either part changed to another value, no matter what value, it would be a mismatch of one 'part' and therefore a distance of one.   So 11-15 would be a distance of one from our example.  11-17 or 13-14 would likewise each be a change of one part from 11-14 and a distance of one.   12-13 or 13-15, however, would each be a mismatch of both (2) parts and a distance of two.   This illustration will apply to any of the two part markers.

The other case is DYS464 which is a four (or more) part marker.   The numbers for it are reported in lowest to highest format which is not necessarily their actual order.   So for DYS464 we have to determine how many markers the two people do not have in common.   Assume DYS464 is 14-14-16-18.   We want to know the genetic distance of 14-16-18-18.   Both have a 14, 16 and 18 in the series -- although not in the same positions -- position doesn't matter on this marker.   So 3 of the 4 numbers are the same, a 1 step mismatch, ergo a distance of one.   12-14-15-16, on the other hand, only has two markers in common, 14 and 16, so we have a two part mismatch or a distance of two.

Come to think of it, I have never seen the values of any multi-part markers reported in anything other than low to high format, no matter how many values.   That being the case I'll go out on a limb just a little and suggest that if we have a two part marker like CDY as 35-39 and we want to compare another marker of 39-40 with it, the distance should be one since we have a mismatch of only one value.

In summary, if it's a recLOH event it's a distance of 1 for the whole event (all multi-copy markers on a given palindromic arm) and if it's not a recLOH event just count each multi-copy marker as a unit, not each part of the marker. Compare the parts but count the marker.

That's the way I see it.


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