RecLOH is a term in genetics that is an abbreviation for "Genetic Recombinational Loss of Heterozygosity".
This is a type of mutation which occurs with DNA by genetic recombination. From a pair of equivalent (homologous), but slightly different (heterozygous) genes, a pair of identical genes results. In this case there is an unreciprocal exchange of genetic code between the chromosomes, in contrast to chromosomal crossover, because genetic information is lost.
Y chromosome DNA
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, since the target is the very same chromosome instead of the homologous one.
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, because it doesn't require pairing between chromosomes. 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".
RecLOH mutations themselves are a sort of repair mechanism for the cell's DNA. If a problem with replication is detected, copying an intact strand of DNA in the place of a strand that is supposed to have the same structure can protect the cell against possible damage in the suspect strand.
Recombination events (RecLOH) can be observed if YSTR databases are searched for twin alleles at three 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.
Once a recLOH mutation has occurred step mutations can still occur in the future on the same markers. The YCAII markers do seem to be quite stable, and within a surname project it is usually the case that that everyone in a group would match on YCAII, even if the group is fairly old.
Can a recLOH be reversed?
A recLOH mutation that replaces one copy of a multi-copy allele with another with a different number of copies is not reversible in the sense that after the recLOH, the two alleles will have the same number of copies. So if another recLOH mutation affecting the two occurs at that time, it won't do anything to change the number of copies at either location. It would still be possible for step mutations and recLOH mutations to occur in the future, and so it is at least possible that the original configuration for the two copies would be restored, but not through a reverse recLOH event. As an example, if you go from 19-21 to 21-21, because the b copy overwrites the a copy, another recLOH is possible with either copy overwriting the other, but you would still have 21-21 after the second recLOH. The 'b' copy would still have the ability to mutate up or down in value in the normal fashion. This is evident in close genetic cousins with a different surname - three in their group have 21,21 but the others are 21,22. YCAII 'b' has had a 'normal' one-step mutation, but the RecLOH copy YCAII 'a' has continued to remain fixed at 21.
If there are more than two copies of a marker, then a single later recLOH mutation affecting the copy that was replaced in the original recLOH could conceivably return it to its earlier configuration, but that would require a recLOH involving another copy of the marker/allele that happened to have the same number of copies as the marker/allele that was overwritten in the first recLOH event. That's pretty unlikely.
Twin alleles or RecLOH?
It can be tough to determine with reasonable certainty whether a recLOH is the cause for twin alleles. Twin alleles can sometimes be the result of step mutations. Another possibility is that twin alleles are not really twin alleles at all, but a single allele that remains after a deletion destroys the other allele. When the lab results are read, a single peak is seen, and it may be interpreted as evidence that the usual two copies are both present and have the same number of repeats. Thomas Krahn at Family Tree DNA does have some tricks for figuring out the causes of twin alleles. Looking at more than one marker from the same palindrome can really help. DYS459, DYS464, and CDY are often affected by the same mutations. If they all appear to be doubled, then recLOH and deletion are both strong possibilities. If they are not all doubled, then the odds favor recLOH, because the alleles that aren't doubled are evidence that at least a part of the palindrome has not been deleted. There are other palindromic markers like DYF399 that are often affected by recLOH events, so Thomas does recommend doing the DYF399X test when trying to sort our recLOH possibilities. The DYS464X test can also help in such cases.
- Thomas Krahn. Recombinational loss of heterozygosity (recLOH). DNA Fingerprint, Germany.
- Understanding recLOH, a discussion on the World Families Forum.
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