Abstract
BackgroundCopy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.ResultsWe found 9634 putative autosomal CNVs across the samples affecting 6.87 % of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR).ConclusionThe analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1713-z) contains supplementary material, which is available to authorized users.
Highlights
Copy number variation is an important dimension of genetic diversity and has implications in development and disease
We used publically available microarray data and identified and characterized copy number (CN) variation in a large sampling of Mus musculus, with 82.5 % of the calls reported for mice that had not been studied for copy number variant (CNV)
We provide several resources for researchers, including a probe list that has been filtered to avoid possible sources of noise in CNV analysis, a list of genes to use as a negative control in CNV studies as well as the CNV calls and strain information generated and analyzed here, all of which will inform future study
Summary
Copy number variation is an important dimension of genetic diversity and has implications in development and disease. The study of CNV associations with complex phenotypes is in high demand with a rich diversity of cost-effective methods [1, 2]; challenges in experimental design lie in the limited availability of relevant tissue samples. The first, array comparative genomic hybridization (aCGH), reports relative copy number to a reference (C57BL/6 J) [3,4,5,6,7,8,9,10] These studies established the extent of copy number variation in the mouse and impact of CNVs on differential expression and phenotypic variation. Taken together, they have characterized around 70 strains of mice, as well as wild-caught mice. While NGS is the method of choice for modern structural variant analysis, it still remains prohibitively expensive for many projects, but has been completed for 18 strains [11, 13, 17]
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