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Series GSE3330 Query DataSets for GSE3330
Status Public on Sep 21, 2005
Title Combined Expression Trait Correlations and Expression Quantitative Trait Locus Mapping
Organism Mus musculus
Experiment type Expression profiling by array
Summary Coordinated regulation of gene expression levels across a series of experimental conditions provides valuable information about the functions of correlated transcripts. To map gene regulatory pathways, we used microarray-derived gene expression measurements in 60 individuals of an F2 sample segregating for diabetes. We performed correlation analysis among ~40,000 expression traits. By combining correlation among expression traits and linkage mapping information, we were able to identify regulatory networks, make functional predictions to uncharacterized genes, and characterize novel members of known pathways. Using 36 seed traits, we found evidence of coordinate regulation of 160 G-protein coupled receptor (GPCR) pathway expression traits. Of the 160 traits, 50 had their major LOD peak within 8 cM of a locus on chromosome 2, and 81 others had a secondary peak in this region. A previously uncharacterized Riken cDNA clone, which showed strong correlation with stearoyl CoA desaturase 1 expression, was experimentally validated to be responsive to conditions that regulate lipid metabolism. Using linkage mapping, we identified multiple genes whose expression is under the control of transcription regulatory loci. Trait-correlation combined with linkage mapping can reveal regulatory networks that would otherwise be missed if we only studied mRNA traits with statistically significant linkages in this small cross. The combined analysis is more sensitive compared with linkage mapping only.
Kendziorski C., M. Chen, M. Yuan, H. Lan, and A.D. Attie. Statistical Methods for Expression Quantitative Trait Loci (eQTL) Mapping. Biometrics, to appear, 2005.
Lan H, Chen M, Flowers JB, Yandell BS, Stapleton DS, et al. (2006) Combined Expression Trait Correlations and Expression Quantitative Trait Locus Mapping. PLoS Genet 2(1): e6.
Keywords: Genetics of gene expression
Overall design The F2-ob/ob mice were chosen from a mapping panel that we created to map diabetes related physiological phenotypes (Stoehr et al. 2000). About 110 of these F2-ob/ob mice were also used to map mRNA abundance traits derived by quantitative real-time RT-PCR (Lan et al. 2003). The sixty F2-ob/ob mice that were used to generate microarray-derived mRNA abundance traits were selected from the 110 mice based on a selective phenotyping algorithm (Jin et al. 2004). The F2-ob/ob mice were housed at weaning at the University of Wisconsin-Madison animal care facility on a 12-h light/dark cycle. Mice were provided Purina Formulab Chow 5008 (6.5% fat) and acidified water ad libitum. Mice were killed at 14 weeks of age by CO2 asphyxiation after a 4-hour fast. The livers, along with other tissues, were immediately foil wrapped and frozen in liquid nitrogen, and subsequently transferred to -80 °C freezers for storage. Liver samples were taken from 29 male and 31 females. Total RNA was isolated with RNAzol Reagent (Tel-Test, Inc.) using a modification of the single-step acid guanidinium isothiocyanate phenol-chloroform extraction method according to the manufacturer's protocol. The extracted RNA was purified using RNeasy (Qiagen, Inc.). RNA samples were evaluated by UV spectroscopy for concentration. RNA quality was monitored by visualization on an ethidium bromide-stained denaturing formaldehyde agarose gel. RNA samples were converted to cDNA, and then biotin-labeled cRNA according to Affymetrix Expression Analysis Technical Manual. The labeled samples were hybridized to the M430A, and subsequently the M430B array. The hybridization, washing and scanning steps were carried out by Hong Lan using the Affymetrix core facility at the Gene Expression Center of University of Wisconsin-Madison.
Contributor(s) Lan H, Chen M, Byers JE, Yandell BS, Stapleton DS, Mata CM, Mui ET, Flowers MT, Schueler KL, Manly KF, Williams RW, Kendziorski CM, Attie AD
Citation(s) 16424919
Submission date Sep 20, 2005
Last update date Jan 08, 2019
Contact name Alan D Attie
Phone 608-262-4705
Fax 608-263-9609
Organization name University of Wisconsin-Madison
Department Biochemistry
Lab Attie
Street address 433 Babcock Drive
City Madison
State/province WI
ZIP/Postal code 53706
Country USA
Platforms (2)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
GPL340 [MOE430B] Affymetrix Mouse Expression 430B Array
Samples (120)
GSM75026 F2-ob/ob(A) 002
GSM75027 F2-ob/ob(A) 012
GSM75028 F2-ob/ob(A) 022
BioProject PRJNA93233

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Supplementary file Size Download File type/resource
GSE3330_B6BTBRlivergenotype110mice.txt 59.7 Kb (ftp)(http) TXT
GSE3330_B6BTBRlivergenotype60mice.txt 34.4 Kb (ftp)(http) TXT
GSE3330_F2genotype60mice145markers.txt 19.1 Kb (ftp)(http) TXT
GSE3330_F2liverPhenotypeHeaders.txt 2.1 Kb (ftp)(http) TXT

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