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Letter

Significant gene content variation characterizes the genomes of inbred mouse strains

¹ Lead Discovery, Amgen, South San Francisco, California 94080, USA; ² Metabolic Disorders, Amgen, South San Francisco, California 94080, USA

The contribution to genetic diversity of genomic segmental copy number variations (CNVs) is less well understood than that of single-nucleotide polymorphisms (SNPs). While less frequent than SNPs, CNVs have greater potential to affect phenotype. In this study, we have performed the most comprehensive survey to date of CNVs in mice, analyzing the genomes of 42 Mouse Phenome Consortium priority strains. This microarray comparative genomic hybridization (CGH)-based analysis has identified 2094 putative CNVs, with an average of 10 Mb of DNA in 51 CNVs when individual mouse strains were compared to the reference strain C57BL/6J. This amount of variation results in gene content that can differ by hundreds of genes between strains. These genes include members of large families such as the major histocompatibility and pheromone receptor genes, but there are also many singleton genes including genes with expected phenotypic consequences from their deletion or amplification. Using a whole-genome association analysis, we demonstrate that complex multigenic phenotypes, such as food intake, can be associated with specific copy number changes.

E-mail gcutler{at}amgen.com; fax (650) 244-2554.

[Supplemental material is available online at www.genome.org. The sequence data from this study have been submitted to NCBI GEO under accession no. GSE9186.]

Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.6754607

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