Spontaneous mutations recovered as mosaics in the mouse specific-locus test

Area of Science:

• Genetics
• Molecular Biology
• Radiation Biology

Background:

• The specific-locus test (SLT) is a standard method for detecting new mutations in mice.
• Spontaneous mutations can appear as singletons or mosaics, with mosaics potentially masked in parents.

Purpose of the Study:

• To investigate the origin and implications of mosaic mutations detected by the SLT.
• To evaluate the impact of including mosaics on mutation rate calculations.

Main Methods:

• Analysis of spontaneous mutations (singleton and mosaic) in mouse models using the SLT.
• Characterization of mutation timing within the germline (perigametic interval vs. mitotic divisions).

Main Results:

• Evidence suggests most SLT mosaics arise from single-strand mutations in the perigametic interval.
• The spontaneous mutation rate in the perigametic interval is significantly higher than in pregametic mitotic divisions.
• Including mosaics inflates spontaneous mutation frequencies by 1.7-2.2 times.

Conclusions:

• Mosaic mutations likely originate from events post-mitosis and pre-meiosis, distinct from radiation-induced mutations.
• Mosaics should be excluded from radiation-induced germ-line mutation rate calculations.
• Current methods for estimating mutation rates may be overestimated due to mosaic inclusion.