Project description:Domestication leads to a spectrum of striking behavioral changes whose genetic basis remains largely unknown. Silver foxes have been selectively bred for tame and aggressive behaviors for over 50 years at the Institute for Cytology and Genetics in Novosibirsk, Russia. To further understand the genetic basis and molecular mechanisms underlying tame and aggressive behavioral phenotypes segregating in selected strains of the silver fox, we quantified genome-wide gene expression levels using RNA-seq in two selected brain tissues, right prefrontal cortex and basal forebrain, from 12 aggressive and 12 tame individuals. Expression analysis reveals 146 differentially expressed genes in prefrontal cortex between tame and aggressive individuals at a 5% FDR, and 33 hits were found in basal forebrain. These candidates include genes in key pathways known to be critical to neurological processing, such as serotonin and glutamate receptor pathways. The data relate in interesting ways to neurological and pharmacological effects that are actively being studied to understand human aggression. In addition, we identified 31,000 high quality exonic SNPs, 295 of which show significant allele frequency differences between tame and aggressive individuals at an adjust P-value < 0.05 level from gene dropping simulation based on the entire pedigrees. A non-synonymous change in a glutamate receptor, GRM3, is among these significant SNPs, indicating that expression and allele-frequency changes are hitting the same pathways. These changes in expression level and allele frequency might be the direct response to the artificial selection and will help understand the genetic basis of mammalian domestication process.
Project description:mRNA Sequencing was done in whole brain hemispheres of the 75 most tame and 75 most aggressive rats of an F2 intercross of rat lines selected for tame and aggressive behavior towards humans. The brain gene expression levels are associated with 1728 genetic markers across the genome to identify expression QTL (eQTL). Genes whose expression is influenced by the same genetic loci that also influence tameness are candidate genes for tame and aggressive behavior. The list of genetic markers can be found in the supplementary materials of the paper for this study. A series of genotype data spreadsheets and associated data processing protocol are available from http://www.ebi.ac.uk/arrayexpress/files/E-MTAB-2544/E-MTAB-2544.additional.1.zip.
Project description:The application of gene expression profiling is to investigate the pathogenesis of aggressive NFPAs. And to identify biomarkers that could play a key role in aggressive behaviour of NFPAs Gene expression was measured among pituitary glands, non-invasion NFPAs and invasion NFPAs
Project description:Pituitary tumors are generally considered as benign. However, many are invasive (45 to 55%) and some are described as aggressive with a high proliferation rate and short post-operative time to recurrence and 0.2% metastasize. The molecular events associated to the progression of the pituitary tumor toward an aggressive and malignant phenotype is still unresolved. To bring new hypothesis on signaling pathways associated to the tumor progression, we applied a wide genome analysis approach combining transcriptome analysis and CGH analysis on the same 13 prolactin tumours classified as non-invasive (n=5), invasive (n=2) and agressive-invasive tumors (n=6). In 5/6 agressive-invasive tumours a loss of a common region in the p arm of the chromosome 11 was detected. This region extending from position 14.9 to position 46.5 Mb harbours the cytobands 11p15.2, 11p15.1, 11p14.3, 11p14.2, 11p14.1, 11p13, 11p12 and 11p11.2. In 3 of these 5 tumours considered as carcinomas because of the presence of metastasis, an allelic loss is also observed in the 11q arm. The combination of data coming from genome structure exploration and transcriptomic analysis showed that allelic loss impact the expression of genes harbored in the imbalanced region. Data filtering strategy allowed us to highlight among the 139 genes harbored in the 11p region loss, 5 genes (DGKZ, CD44, TSG101, GTF2H1 and HTATIP2) that could be candidate gene for triggering the progression of prolactin tumour toward an aggressive and malignant phenotype. Finally, specific DNA alterations give one molecular argument more to consider agressive-invasive tumour and carcinomas as a distinct step in progression of the pituitary tumours. Copy number analysis of Affymetrix Genome-Wide Human SNP Array 6.0 was performed for 13 prolactin tumors, 6 aggressive-invasive, 2 invasive, 5 non-invasive. The same analysis was performed for one normal pituitary and one genomic DNA called "reference 103" from Affymetrix.
Project description:The pituitary gland exhibits sex differences in its function. Diseases associated with dysregulation of the pituitary are also sex-biased in prevalence. Previous qPCR profiling of puberty-related genes in the pituitary gland revealed increasingly sex-biased expression of genes profiled across pubertal transition. Here, we performed small RNA-seq on total RNA extracted from C57BL/6J mouse pituitary gland of both sexes mice at 4 ages spanning pubertal transition (postnatal days 12, 22, 27, 32) (6 replicates per sex at each age) to examine microRNA (miRNA) regulation of sex differences in gene expression observed. Total RNA was sent to SickKids TCAG core to construct small RNA-seq libraries using NEBNext Small RNA Library Prep Kit according to manufacterer’s protocol. Resulting single-end libraries were sequenced at TCAG core on the Illumina HiSeq 2500 v4 flow cell with SR50 bp. Data obtained was processed using miRDeep2 pipeline to align small RNA-seq reads to the mouse genome (mm10) and to filter for miRNAs.