title: A high-resolution map of segmental DNA copy number variation in the mouse genome.
abstract: Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently recognized source of genetic variability between individuals. The biological consequences of copy number variants (CNVs) are largely undefined. In some cases, CNVs that cause gene dosage effects have been implicated in phenotypic variation. CNVs have been detected in diverse species, including mice and humans. Published studies in mice have been limited by resolution and strain selection. We chose to study 21 well-characterized inbred mouse strains that are the focus of an international effort to measure, catalog, and disseminate phenotype data. We performed comparative genomic hybridization using long oligomer arrays to characterize CNVs in these strains. This technique increased the resolution of CNV detection by more than an order of magnitude over previous methodologies. The CNVs range in size from 21 to 2,002 kb. Clustering strains by CNV profile recapitulates aspects of the known ancestry of these strains. Most of the CNVs (77.5%) contain annotated genes, and many (47.5%) colocalize with previously mapped segmental duplications in the mouse genome. We demonstrate that this technique can identify copy number differences associated with known polymorphic traits. The phenotype of previously uncharacterized strains can be predicted based on their copy number at these loci. Annotation of CNVs in the mouse genome combined with sequence-based analysis provides an important resource that will help define the genetic basis of complex traits.
authors.affiliation: Department of Medicine, Division of Oncology, Stem Cell Biology Section, Washington University, St. Louis, Missouri, United States of America. graubert@medicine.wustl.edu
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Graubert
authors.forename: Patrick
authors.initials: P
authors.lastname: Cahan
authors.forename: Deepa
authors.initials: D
authors.lastname: Edwin
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Selzer
authors.forename: Todd A
authors.initials: TA
authors.lastname: Richmond
authors.forename: Peggy S
authors.initials: PS
authors.lastname: Eis
authors.forename: William D
authors.initials: WD
authors.lastname: Shannon
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: James M
authors.initials: JM
authors.lastname: Cheverud
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
mesh_terms: D000818:Animals; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D016000:Cluster Analysis; D015342:DNA Probes / Q000378:metabolism; D030541:Databases, Genetic; D018628:Gene Dosage / Q000235:genetics*; D014644:Genetic Variation; D016678:Genome / Q000235:genetics*; D005854:Germ Cells / Q000378:metabolism; D051379:Mice / Q000235:genetics*; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D015342:DNA Probes