Characterization of a highly unstable mouse minisatellite locus: evidence for somatic mutation during early development.
A highly unstable mouse minisatellite locus, Ms6-hm, has been identified in mouse DNA fingerprints produced by cross-hybridization with human minisatellite probe 33.6. A 7-kb allele of Ms6-hm was cloned from a C57BL/6J mouse and collapsed to a 400-bp plasmid insert on propagation in Escherichia coli due to loss of the majority of minisatellite repeat units. Sequence analysis revealed that Ms6-hm has evolved by amplification within a member of the MT (mouse transcript) family of interspersed repetitive elements. Linkage analysis localized Ms6-hm near the brown coat color gene (b) on chromosome 4. Multiallelism and heterozygosity at this locus within inbred strains result from a high germline mutation rate to new-length alleles (2.5% per gamete). Mice mosaic for cells carrying a nonparental allele in somatic tissue, and in some cases also in the germline, provide evidence for additional, somatic, mutation events at Ms6-hm. In two mosaic mice the fraction of cells containing the nonparental allele has been shown to be indistinguishable in different adult tissues. These somatic mutation events at Ms6-hm must therefore occur very early in development, preceding the allocation of somatic lineages, and the same pool of primitive ectoderm cells must contribute equally to all somatic tissues. Under low-stringency hybridization conditions the collapsed subclone of Ms6-hm cross-hybridizes to other unstable loci in the mouse genome to generate a novel and highly individual specific mouse DNA fingerprint.
Kelly
R
R
Department of Genetics, University of Leicester, United Kingdom.
Bulfield
G
G
Collick
A
A
Gibbs
M
M
Jeffreys
A J
AJ
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004276:DNA, Satellite / Q000235:genetics*; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics* / Q000254:growth & development; D008969:Molecular Sequence Data; D009154:Mutation; D009710:Nucleotide Mapping; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping
D004276:DNA, Satellite