Characterization of the quantitative trait locus for haloperidol-induced catalepsy on distal mouse chromosome 1.
We report here the confirmation of the quantitative trait locus for haloperidol-induced catalepsy on distal chromosome (Chr) 1. We determined that this quantitative trait locus was captured in the B6.D2-Mtv7a/Ty congenic mouse strain, whose introgressed genomic interval extends from approximately 169.1 to 191.3 Mb. We then constructed a group of overlapping interval-specific congenic strains to further break up the interval and remapped the locus between 177.5 and 183.4 Mb. We next queried single nucleotide polymorphism (SNP) data sets and identified three genes with nonsynonymous coding SNPs in the quantitative trait locus. We also queried two brain gene expression data sets and found five known genes in this 5.9-Mb interval that are differentially expressed in both whole brain and striatum. Three of the candidate quantitative trait genes were differentially expressed using quantitative real-time polymerase chain reaction analyses. Overall, the current study illustrates how multiple approaches, including congenic fine mapping, SNP analysis and microarray gene expression screens, can be integrated both to reduce the quantitative trait locus interval significantly and to detect promising candidate quantitative trait genes.
Hofstetter
J R
JR
Department of Veterans Affairs, Richard L. Roudebush Medical Center, Indianapolis, IN 46202, USA. jhofstet@iupui.edu
Hitzemann
R J
RJ
Belknap
J K
JK
Walter
N A R
NA
McWeeney
S K
SK
Mayeda
A R
AR
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D003342:Corpus Striatum / Q000473:pathology*; D003433:Crosses, Genetic; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D006220:Haloperidol / Q000633:toxicity*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D018895:Microsatellite Repeats; D020411:Oligonucleotide Array Sequence Analysis; D011110:Polymorphism, Genetic; D011187:Posture; D040641:Quantitative Trait Loci; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D013045:Species Specificity
D012313:RNA; D004247:DNA; D006220:Haloperidol