Tetrad analysis shows that gene conversion is the major mechanism involvedin mutation at the human minisatellite MS1 integrated in Sacccharomyces cerevisiae

Minisatellites are arrays of tandemly repeated DNA sequences which occur at thousands of locations in the human genome. They are frequently hypervaria ble with respect to allele length as a result of high rates of complex and incompletely understood recombination-based germline mutation events that a lter the repeat copy number. MS1 is one of the most variable minisatellites so far isolated from the human genome. We have integrated MS1, flanked by synthetic markers, in the vicinity of a hot spot for meiotic double-strand breaks upstream of the LEU2 locus in chromosome III of Saccharomyces cerevi siae. Here we present the first tetrad analysis of mutations at a human min isatellite locus. The data showed that mutant alleles occur as single mutan ts in one of the spores in a tetrad. also when the mutant structure was the result of a combination of intra- and inter-allelic rearrangements. The co nversional transfer of repeat units from one allele to the other was associ ated with flanking marker conversion which always involved the same flank o f the minisatellite. The results demonstrate that conversion is the predomi nant mechanism by which minisatellite alleles mutate to new lengths, and al so support the assumption that cis-acting elements are involved in the regu lation of the mutational process in humans.