Spontaneous microdeletions and microinsertions in a transgenic mouse mutation detection system: analysis of age, tissue, and sequence specificity

@article{Halangoda2001SpontaneousMA,
  title={Spontaneous microdeletions and microinsertions in a transgenic mouse mutation detection system: analysis of age, tissue, and sequence specificity},
  author={Asanga Halangoda and Jennifer Still and Kathleen A. Hill and Steve S. Sommer},
  journal={Environmental and Molecular Mutagenesis},
  year={2001},
  volume={37}
}
A total of 3497 independent spontaneous mutations were examined using the Big Blue® transgenic mouse mutation detection system. Base substitutions predominate, although 16% of somatic and germline mutations are microdeletions, microinsertions, or deletions combined with insertions. The pattern of microdeletions and microinsertions is similar in both the lacI transgene and the human p53 gene. Single‐base deletions (D1) and insertions (I1) are evenly distributed in the lacI transgene, whereas… 
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Somatic microindels in human cancer: the insertions are highly error-prone and derive from nearby but not adjacent sense and antisense templates.
TLDR
The data reveal that the inserted sequences derive from nearby but not adjacent sequences in contrast to the slippage that characterizes the great majority of pure microinsertions, raising the question of whether microindels are 'scars' from the bypass of large DNA adducts by a translesional polymerase, e.g. the 'Tarzan model' presented herein.
Somatic microindels: analysis in mouse soma and comparison with the human germline
TLDR
The mouse somatic microindels have characteristics similar to those of human germlineMicroindels in Big Blue mice are consistent with similar causative mechanisms in mouse and human, and in soma and germline.
Preferential occurrence of 1–2 microindels
TLDR
It is speculated that certain error‐prone polymerases may be responsible for the preferential occurrence of 1–2 microindels in both somatic tissues and germ cells.
Evidence for mutation showers
Mutants in the Big Blue transgenic mouse system show spontaneous clustered multiple mutations with unexpectedly high frequency, consistent with chronocoordinate events. We tested the prediction that…
Relatively high rates of G:C → A:T transitions at CpG sites were observed in certain epithelial tissues including pancreas and submaxillary gland of adult big blue® mice
TLDR
A comprehensive review of lacI spontaneous mutation patterns in young adult mice and rats identified additional examples of this mutational bias and an overarching observation about spontaneous mutation frequency in adult tissues of the mouse remains one of stability.
Mutation rates in the dystrophin gene: A hotspot of mutation at a CpG dinucleotide
TLDR
An analysis of mutations was performed in 141 Duchenne muscular dystrophy patients previously found to be negative for large deletions by standard multiplex PCR assays, finding a hotspot of mutation in the dystrophin gene at a CpG dinucleotide and an altered size distribution of microdeletions.
Context of deletions and insertions in human coding sequences
TLDR
Comprehensive analysis of mutability of all possible contexts of lengths four, six, and eight indicates a substantially elevated deletion rate within YYYTG and similar sequences, which is one of the two contexts revealed by the hot spots.
Fragile X repeats are potent inducers of complex, multiple site rearrangements in flanking sequences in Escherichia coli.
Human diallelic insertion/deletion polymorphisms.
TLDR
The identification and characterization of 2,000 human diallelic insertion/deletion polymorphisms (indels) distributed throughout the human genome found that new alleles were generally lower in frequency than old alleles.
Mutation frequency is not elevated in the cerebellum of harlequin/Big Blue(®) mice but Class II deletions occur preferentially in young harlequin cerebellum.
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References

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