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Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex-specific susceptibility and severity of neurological disorders.

Identifying sex differences in gene expression within the brain is critical for determining why multiple neurological and behavioral disorders differentially affect males and females. Several disorders are more common or severe in males (e.g., autism and schizophrenia) or in females (e.g., Alzheimer's disease and depression). We analyzed transcriptomic data from the mouse hippocampus of six inbred strains (129S1/SvImJ, A/J, C57BL/6J, DBA/1J, DBA/2J, and PWD/Ph) to provide a perspective on differences between male and female gene expression. Our data show that 1) gene expression differences in males vs. females varies substantially across the strains, 2) only a few genes are differentially expressed across all of the strains (termed core genes), and 3) >2,600 genes differ in the individual strain comparisons (termed noncore genes). We found that DBA/2J uniquely has a substantial majority (89%) of differentially expressed genes (DEGs) that are more highly expressed in females than in males (female-biased); 129/SvImJ has a majority (69%) of DEGs that are more highly expressed in males. To gain insight into the function of the DEGs, we examined gene ontology and pathway and phenotype enrichment and found significant enrichment in phenotypes related to abnormal nervous system morphology and physiology, among others. In addition, several pathways are enriched significantly, including Alzheimer's disease (AD), with 32 genes implicated in AD, eight of which are male-biased. Three of the male-biased genes have been implicated in a neuroprotective role in AD. Our transcriptomic data provide new insight into the possible genetic bases for sex-specific susceptibility and severity of brain disorders. J. Comp. Neurol. 524:2696-2710, 2016. © 2016 Wiley Periodicals, Inc.

Pubmed ID: 26917114 RIS Download

Mesh terms: Animals | Female | Gene Expression Profiling | Gene Regulatory Networks | Hippocampus | Male | Mice | Mice, 129 Strain | Mice, Inbred C57BL | Mice, Inbred DBA | Mice, Inbred Strains | Nervous System Diseases | Severity of Illness Index | Sex Characteristics | Species Specificity

Data used in this publication

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Associated grants

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Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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Integrated Animals

Integrated Animals is a virtual database currently indexing available animal strains and mutants from: AGSC (Ambystoma), BCBC (mice), BDSC (flies), CWRU Cystic Fibrosis Mouse Models (mice), DGGR (flies), FlyBase (flies), IMSR (mice), MGI (mice), MMRRC (mice), NSRRC (pig), NXR (Xenopus), RGD (rats), Sperm Stem Cell Libraries for Biological Research (rats), Tetrahymena Stock Center (Tetrahymena), WormBase (worms), XGSC (Xiphophorus), ZFIN (zebrafish), and ZIRC (zebrafish).

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cufflinks

Assembles transcripts, estimates their abundances, and tests for differential expression and regulation in RNA-Seq samples.

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DESeq

A software for differential gene expression analysis based on the negative binomial distribution. It estimates variance-mean dependence in count data from high-throughput sequencing assays and tests for differential expression.

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easyRNASeq

Software that calculates the coverage of high-throughput short-reads against a genome of reference and summarizes it per feature of interest (e.g. exon, gene, transcript). The data can be normalized as ''RPKM'' or by the ''DESeq'' or ''edgeR'' package.

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Kyoto Encyclopedia of Genes and Genomes Expression Database

A repository of microarray gene expression profile data for Synechocystis PCC6803 (syn), Bacillus subtilis (bsu), Escherichia coli W3110 (ecj), Anabaena PCC7120 (ana), and other species contributed by the Japanese research community.

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GeneMANIA

Data analysis service to predict the function of your favorite genes and gene sets. Indexing 1,421 association networks containing 266,984,699 interactions mapped to 155,238 genes from 7 organisms. GeneMANIA interaction networks are available for download in plain text format. GeneMANIA finds other genes that are related to a set of input genes, using a very large set of functional association data. Association data include protein and genetic interactions, pathways, co-expression, co-localization and protein domain similarity. You can use GeneMANIA to find new members of a pathway or complex, find additional genes you may have missed in your screen or find new genes with a specific function, such as protein kinases. Your question is defined by the set of genes you input. If members of your gene list make up a protein complex, GeneMANIA will return more potential members of the protein complex. If you enter a gene list, GeneMANIA will return connections between your genes, within the selected datasets. GeneMANIA suggests annotations for genes based on Gene Ontology term enrichment of highly interacting genes with the gene of interest. GeneMANIA is also a gene recommendation system. GeneMANIA is also accessible via a Cytoscape plugin, designed for power users. Platform: Online tool, Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible

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Trimmomatic

Performs a variety of useful trimming tasks for illumina paired-end and single ended data.

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WebGestalt: WEB-based GEne SeT AnaLysis Toolkit

A web-based gene set analysis toolkit designed for functional genomic, proteomic, and large-scale genetic studies from which large number of gene lists (e.g. differentially expressed gene sets, co-expressed gene sets etc) are continuously generated. WebGestalt incorporates information from different public resources and provides a way for biologists to make sense out of gene lists. This version of WebGestalt supports eight organisms, including human, mouse, rat, worm, fly, yeast, dog, and zebrafish.

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SAMTOOLS

Various software utilities for manipulating alignments in the SAM (Sequence Alignment/Map) format, a flexible generic format for storing nucleotide sequence alignment, including sorting, merging, indexing and generating alignments in a per-position format. The parts that relevant to genetic analysis include SNP and indel callings.

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FastQC

Software that provides a simple way to do some quality control checks on raw sequence data coming from high throughput sequencing pipelines.

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GenePattern

A powerful genomic analysis platform that provides access to hundreds of tools for gene expression analysis, proteomics, SNP analysis, flow cytometry, RNA-seq analysis, and common data processing tasks. A web-based interface provides easy access to these tools and allows the creation of multi-step analysis pipelines that enable reproducible in silico research.

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REViGO

Web server that summarizes lists of Gene Ontology terms by removing redundant terms and visualizing the remaining ones in scatterplots, interactive graphs, treemaps, or tag clouds. Platform: Online tool

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GOrilla: Gene Ontology Enrichment Analysis and Visualization Tool

A tool for identifying and visualizing enriched GO terms in ranked lists of genes. It can be run in one of two modes: * Searching for enriched GO terms that appear densely at the top of a ranked list of genes or * Searching for enriched GO terms in a target list of genes compared to a background list of genes.

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TopHat

A fast splice junction mapper for RNA-Seq reads.

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