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Vol. 9, Issue 2, 130-136, February 1999

LETTER
Comparative Sequence Analysis of Human Minisatellites Showing Meiotic Repeat Instability

John Murray, Jérôme Buard, David L. Neil, Edouard Yeramian,2 Keiji Tamaki, Caroline Hollies, and Alec J. Jeffreys1

Department of Genetics, University of Leicester, Leicester LE1 7RH, UK; 2 Unité de Physico-Chimie, Institut Pasteur, 75015 Paris, France

The highly variable human minisatellites MS32 (D1S8), MS31A (D7S21), and CEB1 (D2S90) all show recombination-based repeat instability restricted to the germline. Mutation usually results in polar interallelic conversion or occasionally in crossovers, which, at MS32 at least, extend into DNA flanking the repeat array, defining a localized recombination hotspot and suggesting that cis-acting elements in flanking DNA can influence repeat instability. Therefore, comparative sequence analysis was performed to search for common flanking elements associated with these unstable loci. All three minisatellites are located in GC-rich DNA abundant in dispersed and tandem repetitive elements. There were no significant sequence similarities between different loci upstream of the unstable end of the repeat array. Only one of the three loci showed clear evidence for putative coding sequences near the minisatellite. No consistent patterns of thermal stability or DNA secondary structure were shared by DNA flanking these loci. This work extends previous data on the genomic environment of minisatellites. In addition, this work suggests that recombinational activity is not controlled by primary or secondary characteristics of the DNA sequence flanking the repeat array and is not obviously associated with gene promoters as seen in yeast.

[The sequence data described in this paper have been submitted to the GenBank data library under accession nos. AF048727 (CEB1), AF048728 (MS31A), and AF048729 (MS32).]

1   Corresponding author.

9:130-136 ©1999 by Cold Spring Harbor Laboratory Press  ISSN 1088-9051/99 $5.00
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