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In Silico Whole Genome Association Scan for Murine Prepulse Inhibition
- Source :
- PLoS ONE, PLoS ONE, Vol 4, Iss 4, p e5246 (2009)
- Publication Year :
- 2009
- Publisher :
- Public Library of Science, 2009.
-
Abstract
- BackgroundThe complex trait of prepulse inhibition (PPI) is a sensory gating measure related to schizophrenia and can be measured in mice. Large-scale public repositories of inbred mouse strain genotypes and phenotypes such as PPI can be used to detect Quantitative Trait Loci (QTLs) in silico. However, the method has been criticized for issues including insufficient number of strains, not controlling for false discoveries, the complex haplotype structure of inbred mice, and failing to account for genotypic and phenotypic subgroups.Methodology/principal findingsWe have implemented a method that addresses these issues by incorporating phylogenetic analyses, multilevel regression with mixed effects, and false discovery rate (FDR) control. A genome-wide scan for PPI was conducted using over 17,000 single nucleotide polymorphisms (SNPs) in 37 strains phenotyped. Eighty-nine SNPs were significant at a false discovery rate (FDR) of 5%. After accounting for long-range linkage disequilibrium, we found 3 independent QTLs located on murine chromosomes 1 and 13. One of the PPI positives corresponds to a region of human chromosome 6p which includes DTNBP1, a gene implicated in schizophrenia. Another region includes the gene Tsn which alters PPI when knocked out. These genes also appear to have correlated expression with PPI.Conclusions/significanceThese results support the usefulness of using an improved in silico mapping method to identify QTLs for complex traits such as PPI which can be then be used for to help identify loci influencing schizophrenia in humans.
- Subjects :
- False discovery rate
Linkage disequilibrium
Genotype
Science
In silico
Quantitative Trait Loci
Gene Expression
Single-nucleotide polymorphism
Mice, Inbred Strains
Biology
Quantitative trait locus
Genetics and Genomics/Complex Traits
Genome
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Mice
Quantitative Trait, Heritable
Inbred strain
Animals
Humans
Genetics and Genomics/Genetics of Disease
Phylogeny
Genetics
Mental Health/Schizophrenia and Other Psychoses
Multidisciplinary
Haplotype
Dysbindin
Chromosome Mapping
Computational Biology
Genetics and Genomics
Neural Inhibition
Genetics and Genomics/Bioinformatics
DNA-Binding Proteins
Phenotype
Genes
Dystrophin-Associated Proteins
Schizophrenia
Medicine
Chromosomes, Human, Pair 6
Carrier Proteins
Research Article
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....fbc6ed24d821265105f84bd7491a449b