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Repeat instability at human minisatellites arising from meiotic recombination
A J Jeffreys1, D L Neil, R Neumann
1Department of Genetics, University of Leicester, Leicester LE1 7RH, UK.ajj@le.ac.uk
The EMBO Journal
|July 22, 1998
Summary
Meiotic recombination, including unequal crossover, drives instability in human tandem repeat DNA. This study reveals crossover and conversion mechanisms are linked, suggesting minisatellite instability arises from meiotic recombination processes.
Area of Science:
- Genetics
- Molecular Biology
- Human Genetics
Background:
- Tandem repeat DNA instability is poorly understood, particularly the role of meiotic recombination processes like unequal crossover.
- Minisatellites are prone to mutation, but the underlying mechanisms, especially during meiosis, require further elucidation.
Purpose of the Study:
- To investigate the role of meiotic crossover events in driving instability within human GC-rich minisatellite repeat arrays.
- To characterize the frequency and nature of crossovers (equal and unequal) and their relationship with gene conversion at minisatellite loci.
Main Methods:
- Development of methods to detect meiotic crossovers in human minisatellite DNA from both family studies and sperm DNA.
- Analysis of mutation patterns, including repeat conversion and crossover events, within specific minisatellite repeat arrays.
Main Results:
- Both equal and unequal inter-allelic crossovers were detected at low frequencies in human minisatellite arrays.
- Minisatellite conversion and crossover events exhibit polarity and are co-suppressed in stable alleles, suggesting a common mechanistic origin.
- Crossover rates indicate that unstable minisatellite ends can function as recombination hotspots, even between sequence-heterologous alleles.
Conclusions:
- Minisatellite instability is likely a byproduct of meiotic recombination, with conversion and crossover potentially arising from alternative processing of the same recombination initiation complex.
- The findings provide evidence for a shared mechanism underlying minisatellite conversion and crossover, highlighting the link between meiotic recombination and DNA instability.