GeneSet Information

Tier III GS1086 • Highly upregulated cerebellar genes mapping to Lore QTL intervals in Inbred Long Sleep (ISS)

DESCRIPTION:

Four QTLshave been mapped in ILS and ISS for ethanol induced LORR. Underlying each of these QTLs must be one or more genetic differences (polymorphisms in either gene coding or regulatory regions) influencing ethanol sensitivity. Genome-wide expression profiling in cerebellum was used here to identify candidate genes for regulatory region differences in these two strains. Fifteen differentially expressed genes were found that map to the QTL regions

LABEL:

GeneUpregILSMapLore

SCORE TYPE:

Binary

DATE ADDED:

2008-03-19

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

MacLaren EJ, Bennett B, Johnson TE, Sikela JM

TITLE:

Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs.

JOURNAL:

Mammalian genome : official journal of the International Mammalian Genome Society Feb 2006, Vol 17, pp. 147-56

ABSTRACT:

The Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) mouse strains have a 16-fold difference in duration of loss of the righting response (LORR) following administration of a sedative dose of ethanol. Four quantitative trait loci (QTLs) have been mapped in these strains for this trait. Underlying each of these QTLs must be one or more genetic differences (polymorphisms in either gene coding or regulatory regions) influencing ethanol sensitivity. Because prior studies have tended to focus on differences in coding regions, genome-wide expression profiling in cerebellum was used here to identify candidate genes for regulatory region differences in these two strains. Fifteen differentially expressed genes were found that map to the QTL regions and polymorphisms were identified in the promoter regions of four of these genes by direct sequencing of ILS and ISS genomic DNA. Polymorphisms in the promoters of three of these genes, Slc22a4, Rassf2, and Tax1bp3, disrupt putative transcription factor binding sites. Slc22a4 and another candidate, Xrcc5, have human orthologs that map to genomic regions associated with human ethanol sensitivity in genetic linkage studies. These genes represent novel candidates for the LORR phenotype and provide new targets for future studies into the neuronal processes underlying ethanol sensitivity. PUBMED: 16465594
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Annotation Information

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Gene Expression Regulation (D005786)
Clinical Coding (D059019)
Animals (D000818)
Forecasting (D005544)
Humans (D006801)
Promoter Regions, Genetic (D011401)
DNA (D004247)
Psychiatric Status Rating Scales (D011569)
Genome (D016678)
Mice (D051379)
Gene Expression Profiling (D020869)
Genetic Linkage (D008040)
Quantitative Trait Loci (D040641)
Carrier Proteins (D002352)
Binding Sites (D001665)
Polymorphism, Genetic (D011110)
Antigens, Nuclear (D034961)
Reflex, Righting (D057897)
Oligonucleotide Array Sequence Analysis (D020411)
Mice, Inbred Strains (D008815)
Transcription Factors (D014157)
Membrane Proteins (D008565)
Cerebellum (D002531)
Organization and Administration (D009934)
Regulatory Sequences, Nucleic Acid (D012045)
Hypnotics and Sedatives (D006993)
DNA-Binding Proteins (D004268)
Sleep (D012890)
Ethanol (D000431)
cerebellum (MA:0000198)
sleep (GO:0030431)
transcription factor binding (GO:0008134)
righting reflex (GO:0060013)
binding (GO:0005488)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351