In silico whole genome association scan for murine prepulse inhibition.

<h4>Background</h4>The 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 (Q...

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Autores principales:	Bradley Todd Webb, Joseph L McClay, Cristina Vargas-Irwin, Timothy P York, Edwin J C G van den Oord
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/27e8ce4f95c9468f8c22729a04a775b5
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spelling	oai:doaj.org-article:27e8ce4f95c9468f8c22729a04a775b52021-11-25T06:16:07ZIn silico whole genome association scan for murine prepulse inhibition.1932-620310.1371/journal.pone.0005246https://doaj.org/article/27e8ce4f95c9468f8c22729a04a775b52009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19370154/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The 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.<h4>Methodology/principal findings</h4>We 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.<h4>Conclusions/significance</h4>These 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.Bradley Todd WebbJoseph L McClayCristina Vargas-IrwinTimothy P YorkEdwin J C G van den OordPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5246 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bradley Todd Webb Joseph L McClay Cristina Vargas-Irwin Timothy P York Edwin J C G van den Oord In silico whole genome association scan for murine prepulse inhibition.
description	<h4>Background</h4>The 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.<h4>Methodology/principal findings</h4>We 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.<h4>Conclusions/significance</h4>These 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.
format	article
author	Bradley Todd Webb Joseph L McClay Cristina Vargas-Irwin Timothy P York Edwin J C G van den Oord
author_facet	Bradley Todd Webb Joseph L McClay Cristina Vargas-Irwin Timothy P York Edwin J C G van den Oord
author_sort	Bradley Todd Webb
title	In silico whole genome association scan for murine prepulse inhibition.
title_short	In silico whole genome association scan for murine prepulse inhibition.
title_full	In silico whole genome association scan for murine prepulse inhibition.
title_fullStr	In silico whole genome association scan for murine prepulse inhibition.
title_full_unstemmed	In silico whole genome association scan for murine prepulse inhibition.
title_sort	in silico whole genome association scan for murine prepulse inhibition.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/27e8ce4f95c9468f8c22729a04a775b5
work_keys_str_mv	AT bradleytoddwebb insilicowholegenomeassociationscanformurineprepulseinhibition AT josephlmcclay insilicowholegenomeassociationscanformurineprepulseinhibition AT cristinavargasirwin insilicowholegenomeassociationscanformurineprepulseinhibition AT timothypyork insilicowholegenomeassociationscanformurineprepulseinhibition AT edwinjcgvandenoord insilicowholegenomeassociationscanformurineprepulseinhibition
_version_	1718413971949617152

In silico whole genome association scan for murine prepulse inhibition.

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