Genomic variants in an inbred mouse model predict mania-like behaviors

PloS One
Michael C SaulStephen C Gammie

Abstract

Contemporary rodent models for bipolar disorders split the bipolar spectrum into complimentary behavioral endophenotypes representing mania and depression. Widely accepted mania models typically utilize single gene transgenics or pharmacological manipulations, but inbred rodent strains show great potential as mania models. Their acceptance is often limited by the lack of genotypic data needed to establish construct validity. In this study, we used a unique strategy to inexpensively explore and confirm population allele differences in naturally occurring candidate variants in a manic rodent strain, the Madison (MSN) mouse strain. Variants were identified using whole exome resequencing on a small population of animals. Interesting candidate variants were confirmed in a larger population with genotyping. We enriched these results with observations of locomotor behavior from a previous study. Resequencing identified 447 structural variants that are mostly fixed in the MSN strain relative to control strains. After filtering and annotation, we found 11 non-synonymous MSN variants that we believe alter protein function. The allele frequencies for 6 of these variants were consistent with explanatory variants for the Madison strain's ph...Continue Reading

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Datasets Mentioned

BETA
SRP040655

Methods Mentioned

BETA
genotyping
transgenic
PCR
electrophoresis
PCRs

Software Mentioned

Genome Analysis Tool Kit ( GATK )
R
DAVID
Multiz
Bowtie
GPS
Ensembl
Picard
UCSC Genome Browser
CASAVA

Related Concepts

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