Mar 22, 2019 - 10:10 PM
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Recombinational Loss of Heterozygosity (recLOH)

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OK, I'll try to explain the recombinational loss of heterozygosity (recLOH) in pictures:

If we have a palindromic region (that means, that the DNA sequence has a loop and the ends of the loop can be put parallel next to each other and the parallel ends have nearly exatly the same DNA sequence, in other words an inverted repeat) we can model a simple structure like this:

AAA... is the forward strand, BBB... is the backward strand and LLL...
is the loop.

A real *deletion* would look like this:

This configuration will not be observed very frequently, because the cell will immediately try to repair this by a recombinational process.

In this process the cell tries to copy the backward strand and insert it in the deleted region. We end up with this structure:

If we have a duplicated STR marker in the region of the recombination then we observe a *recombinational loss of heterozygosity* (recLOH). E.g. first we have the alleles 15-18, after the recombination we have 18-18.

In very few cases we can also observe a complete *inversion* of the whole loop. We start from the first (original) structure above and simply turn the loop around at one point of the palindromic sequence:

This is the mechanism that Ralf Kittler proposed for the inversion of the DYS385 alleles when they swaped the direction from R1* to R1b. The STR repeats of DYS385 are still left of the breakpoint, but the differenciating primers are right of the breakpoint, actually at the beginning of the loop.

In general such recombination processes are not completely understood. Scientists know that complex proteins are at work (a simple example is the recA protein of E. coli, which is already extensively studied), but little is known about the regulation mechanism that identifies "damaged" DNA regions and initiates the recombinational repair. For a genealogist theese recombinational events can be considered as timeline markers. They seem to happen more frequently than SNP mutations but less frequently than STR mutations. So they give us the chance to study the time-gap in between SNPs and STRs. Several project coordinators have previously reported recLOH events at duplicated markers. Now it is time to collect those informations and try to measure such parameters like recLOH frequencies, length of recombination sites, structure of real deletions etc.

Frequency of recLOH events

Rozen et al. (Nature 2003, V423, p. 873 ff) has calculated the frequency of gene conversion by a steady-state balance between new mutations that create differences between arms, and gene-conversion events that erase these differences. He ends up with a frequency of 0.000011 gene conversions per duplicated nucleotide per year. Over the 5.4 Mb in human MSY palindromes (2.7 x 10^6 duplicated nucleotides), an average of about 600 duplicated nucleotides have undergone arm-to-arm gene conversion for every son born in recent human evolution.

There are some new tools that may help to find out such parameters:
1.) The DYS385a*/b* Kittler protocol
2.) The DYS464X analysis (in R1b)
3.) The asymetric DYF399S1 marker
4.) All the duplicated and quadruplicated markers: DYS385, DYS413, DYS459, YCAII, DYS464, DYS724 (=CDY), DYS725, DYF385S1

Further information on the web:

  • John Mc Ewans DYS464X/DYF399 page
  • RecLOH at Wikipedia

  • I hope this will help to understand the new approaches a little bit better now.

    Thomas Krahn


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