Identification of quantitative trait loci for prepulse inhibition in rats.
BACKGROUND
Schizophrenia is a common and debilitating psychiatric disorder that is partially under genetic control. Because of difficulties in mapping the genes that influence susceptibility to schizophrenia in humans, there has been substantial interest in mapping genes that control endophenotypes for schizophrenia in both human and rodent populations. Deficient prepulse inhibition (PPI) of the startle response has shown promise as an endophenotype for schizophrenia, as well as several other psychiatric disorders.


METHODS
Brown Norway (BN/SsNHsd) and Wistar Kyoto (WKY/lj-cr) rats were used because they show a large, unconfounded difference in PPI. We used interval mapping methods to identify quantitative trait loci (QTL) for PPI in a backcross population.


RESULTS
We identified a QTL on chromosome 2 with a LOD score of 3.63 and a suggestive QTL on chromosome 18 with a LOD score of 2.71.


CONCLUSIONS
Both of the identified regions contain several candidate genes. Furthermore, the implicated rat chromosomes are syntenic with human chromosomal regions that have been reported to contain QTL for schizophrenia, bipolar disorder, and Tourette's syndrome. These results identify the chromosomal location of gene(s) that modulate an endophenotype for schizophrenia, and other psychiatric disorders, and may provide a shortcut to identifying specific genes and/or biochemical pathways involved in human psychiatric diseases.
Palmer
Abraham A
AA
Department of Pharmacology, University of California San Diego, La Jolla 92093, USA. aap2010@columbia.edu
Breen
Laura L
LL
Flodman
Pamela
P
Conti
Lisa H
LH
Spence
M Anne
MA
Printz
Morton P
MP
D000161:Acoustic Stimulation; D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D008126:Lod Score; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D011914:Rats, Inbred BN; D011921:Rats, Inbred WKY; D013216:Reflex, Startle / Q000235:genetics*; D013045:Species Specificity
D005819:Genetic Markers