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Series GSE10656 Query DataSets for GSE10656
Status Public on Mar 09, 2009
Title The impact of copy number variation on local gene expression in mouse hematopoietic stem and progenitor cells
Organism Mus musculus
Experiment type Genome variation profiling by genome tiling array
Expression profiling by array
Summary The extent to which differences in germ line DNA copy number contribute to natural phenotypic variation is unknown. We analyzed the copy number content of the mouse genome to a sub-10 kb resolution. We identified over 1,300 copy number variant regions (CNVRs), most of which are < 10 kb in length, are found in more than one strain, and, in total, span 3.2% (85 Mb) of the genome. To assess the potential functional impact of copy number variation, we mapped expression profiles of purified hematopoietic stem and progenitor cells, adipose tissue and hypothalamus to CNVRs in cis. Of the more than 600 significant associations between CNVRs and expression profiles, most map to CNVRs outside of the transcribed regions of genes. In hematopoietic stem/progenitor cells, up to 28% of strain-dependent expression variation is associated with copy number variation, supporting the role of germ line CNVs as major contributors to natural phenotypic variation in the laboratory mouse.
 
Overall design To map the CNV content of the mouse genome, we selected 17 Tier 1-3 Mouse Phenome Project strains and three additional strains of biomedical interest, representing all major inbred lineages. We performed comparative genomic hybridization using a long-oligonucleotide array containing 2,149,887 probes evenly spaced across the reference genome with a median inter-probe spacing of 1,015 bases. Labeling, hybridization, washing and array imaging were performed as previously described (PMID:16075461). We performed segmentation using wuHMM, a Hidden Markov Model algorithm that utilizes sequence-level information and can detect CNVs less than 5 kb in length (fewer than five probes) at a low false positive rate (PMID:18334530). To estimate the overall impact of CNV on gene expression in vivo, we performed expression profiling of hematopoietic stem/progenitors cells using the Illumina Mouse Beadchip-6v1 platform. See manuscript for further details.
 
Contributor(s) Cahan P, Li Y, Izumi M, Graubert TA
Citation(s) 19270704, 20861859
Submission date Feb 27, 2008
Last update date Jan 18, 2013
Contact name Patrick Cahan
E-mail patrick.cahan@jhmi.edu
Organization name Johns Hopkins University School of Medicine
Department ICE and Biomedical Engineering
Lab Cahan Lab
Street address 733 North Broadway, MRB 653
City Baltimore
State/province MD
ZIP/Postal code 21205
Country USA
 
Platforms (2)
GPL6436 NimbleGen Mouse 2.1M NCBI36
GPL8081 WU Mouse_Illumina_46k_v6-1.1
Samples (66)
GSM265502 129X1/SvJ 119905_SOM01GFG
GSM265503 A/J 119920_SOM01GFF
GSM265504 FVB/NJ 119969_SOM01GFJ
Relations
BioProject PRJNA107621

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE10656_RAW.tar 1.4 Gb (http)(custom) TAR (of PAIR)
Raw data included within Sample table
Processed data included within Sample table

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