Recurrent DNA copy number variation in the laboratory mouse

Area of Science:

• Genomics
• Evolutionary Biology
• Population Genetics

Background:

• Genetic diversity is influenced by variations in DNA copy number.
• The mechanisms and rates of spontaneous copy number variation (CNV) across generations are not well understood.
• Understanding CNV origins is crucial for interpreting natural variation and evolutionary processes.

Purpose of the Study:

• To investigate the genome-wide patterns and mutation rates of spontaneous copy number variation (CNV) in the laboratory mouse.
• To determine if CNV arises randomly or through nonrandom processes like recurrent mutation.
• To assess the impact of CNV on gene dosage and its potential role in natural variation.

Main Methods:

• Genome-wide analysis of spontaneous copy number variation (CNV) using high-resolution microarrays.
• Identification of 38 CNVs across 14 inbred colonies of the C57BL/6 mouse strain.
• Examination of identified CNV loci in 12 additional mouse strains to assess recurrence.

Main Results:

• Identified 38 distinct copy number variations (CNVs) across the mouse genome.
• Found that 18 out of 38 CNVs resulted from recurrent mutation, indicating a nonrandom origin.
• Observed significant variation in mutation rates across different genomic loci, spanning four orders of magnitude.
• Discovered recurrent CNVs affecting 43 genes, which fluctuate in copy number over hundreds of generations.

Conclusions:

• Copy number variation (CNV) arises through nonrandom processes, particularly recurrent mutation.
• The rate of CNV formation varies substantially across the genome.
• Recurrent CNVs affecting multiple genes can emerge rapidly, raising questions about their contribution to adaptive evolution and natural variation.