Recurrent DNA copy number variation in the laboratory mouse

We have conducted a genome-wide analysis of spontaneous copy number variation (CNV) in the laboratory mouse. We used high resolution microarrays to identify 38 CNVs between 14 colonies of the C57BL/6 strain spanning ~967 generations of inbreeding, and examined these loci in 12 additional strains. It is clear from our results that many CNVs arise through a highly non-random process: 18 of 38 were the product of recurrent mutation, and rates of change vary roughly four orders of magnitude across different loci. These recurrent CNVs are distributed throughout the genome, affect 43 genes, and fluctuate in copy number over mere hundreds of generations, observations that raise questions about their contribution to natural variation. Keywords: comparative genomic hybridization, DNA copy number variation, structural variation, inbred mice, spontaneous mutation rate IIn order to verify, precisely map, and accurately score spontaneous copy number mutations identified by our previous analysis using representational oligonucleotide microarray analysis (ROMA, see related submission), we performed comparative genome hybridization (CGH) for each strain using high resolution oligonucleotide microarrays (tiling arrays). These arrays contain 385,213 probes placed at high density (~1 per 46 bp) across each locus identified by ROMA. We performed at least two independent experiments for each of 25 strains, each compared to a single pedigreed individual of the C57BL6/J strain.