Genome wide profiling of altered gene expression in the neocortex of Alzheimer's disease

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Michelle G. Tan ◽  
Wei-Ting Chua ◽  
Margaret M. Esiri ◽  
A. David Smith ◽  
Harry V. Vinters ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene

P1-226: Alzheimer's Disease Susceptibility Loci: Evidence for Natural Selection and Altered Gene Expression

2011 ◽  
Vol 7 ◽  
pp. S183-S183
Author(s):  
Towfique Raj ◽  
Joshua Shulman ◽  
Lori Chibnik ◽  
Brendan Keenan ◽  
Barbara Stranger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Selection ◽  
Disease Susceptibility ◽  
Susceptibility Loci ◽  
Altered Gene Expression ◽  
Altered Gene

scholarly journals Altered Gene Expression in Alzheimer's Disease Brain Tissue

1989 ◽  
Vol 16 (S4) ◽  
pp. 473-476 ◽  
Author(s):  
Patrick C. May ◽  
Steven A. Johnson ◽  
Judes Poirier ◽  
Martha Lampert-Etchells ◽  
Caleb E. Finch
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sertoli Cells ◽  
Normal Function ◽  
Altered Gene Expression ◽  
Molecular Approaches ◽  
Altered Gene ◽  
And Control ◽  
Sulfated Glycoprotein

ABSTRACT:We review the evidence for altered gene expression in Alzheimer's disease brain and identify alternative molecular approaches for isolating additional novel markers. One marker, pADHC-9, was isolated from a human hippocampal cDNA library by differential screening with AD and control cDNA probes. This clone hybridizes to a 2 Kb RNA which is increased 2 fold in AD hippocampus. The deduced amino acid sequence of pADHC-9 codes for a 52 kDAL protein similar to a testicular sulfated glycoprotein secreted by rat Sertoli cells. The normal function of this protein in brain and whether that function is altered in Alzheimer's disease is unknown.

Altered gene expression and neuropathology in Alzheimer's disease

2006 ◽  
Vol 27 (8) ◽  
pp. 1081-1083 ◽  
Author(s):  
Ivona Brasnjevic ◽  
Harry W.M. Steinbusch ◽  
Christoph Schmitz
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Altered Gene Expression ◽  
Altered Gene

scholarly journals Hippocampal transcriptome-wide association study and neurobiological pathway analysis for Alzheimer’s disease

PLoS Genetics ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. e1009363
Author(s):  
Nana Liu ◽  
Jiayuan Xu ◽  
Huaigui Liu ◽  
Shijie Zhang ◽  
Miaoxin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Meta Analysis ◽  
Hippocampal Volume ◽  
Genome Wide Association ◽  
Novel Genes ◽  
Genome Wide ◽  
Mapping Models

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer’s disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.

Epigenetic drug combination induces genome-wide demethylation and altered gene expression in neuro-ectodermal tumor-derived cell lines

2013 ◽  
Vol 36 (5) ◽  
pp. 351-362 ◽  
Author(s):  
Floor A.M. Duijkers ◽  
Renee X. de Menezes ◽  
Inès J. Goossens-Beumer ◽  
Dominique J.P.M. Stumpel ◽  
Pieter Admiraal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Drug Combination ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Epigenetic Drug ◽  
Altered Gene

scholarly journals Monocyte-specific changes in gene expression implicate LACTB2 and PLIN2 in Alzheimer’s disease

2020 ◽  
Author(s):  
Janet C. Harwood ◽  
Ganna Leonenko ◽  
Rebecca Sims ◽  
Valentina Escott-Price ◽  
Julie Williams ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Studies ◽  
Genetic Data ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Risk Genes ◽  
Genome Wide ◽  
Immune Pathways

AbstractMore than 50 genetic loci have been identified as being associated with Alzheimer’s disease (AD) from genome-wide association studies (GWAS) and many of these are involved in immune pathways and lipid metabolism. Therefore, we performed a transcriptome-wide association study (TWAS) of immune-relevant cells, to study the mis-regulation of genes implicated in AD. We used expression and genetic data from naive and induced CD14+ monocytes and two GWAS of AD to study genetically controlled gene expression in monocytes at different stages of differentiation and compared the results with those from TWAS of brain and blood. We identified nine genes with statistically independent TWAS signals, seven are known AD risk genes from GWAS: BIN1, PTK2B, SPI1, MS4A4A, MS4A6E, APOE and PVR and two, LACTB2 and PLIN2/ADRP, are novel candidate genes for AD. Three genes, SPI1, PLIN2 and LACTB2, are TWAS significant specifically in monocytes. LACTB2 is a mitochondrial endoribonuclease and PLIN2/ADRP associates with intracellular neutral lipid storage droplets (LSDs) which have been shown to play a role in the regulation of the immune response. Notably, LACTB2 and PLIN2 were not detected from GWAS alone.

scholarly journals Silent crickets reveal the genomic footprint of recent adaptive trait loss

2018 ◽  
Author(s):  
Sonia Pascoal ◽  
Judith E. Risse ◽  
Xiao Zhang ◽  
Mark Blaxter ◽  
Timothee Cezard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signal Loss ◽  
Sexual Signal ◽  
Adaptive Trait ◽  
Field Crickets ◽  
Altered Gene Expression ◽  
Genome Wide ◽  
Altered Gene ◽  
High Density Linkage Map ◽  
Mutational Effect

Secondary trait loss is widespread and has profound consequences, from generating diversity to driving adaptation. Sexual trait loss is particularly common. Its genomic impact is challenging to reconstruct because most reversals occurred in the distant evolutionary past and must be inferred indirectly, and questions remain about the extent of disruption caused by pleiotropy, altered gene expression and loss of homeostasis. We tested the genomic signature of recent sexual signal loss in Hawaiian field crickets, Teleogryllus oceanicus. Song loss is controlled by a sex-linked Mendelian locus, flatwing, which feminises male wings by erasing sound-producing veins. This variant spread rapidly under pressure from an eavesdropping parasitoid fly. We sequenced, assembled and annotated the T. oceanicus genome, produced a high-density linkage map, and localised flatwing on the X chromosome. We characterised pleiotropic effects of flatwing, including changes in embryonic gene expression and alteration of another sexual signal, chemical pheromones. Song loss is associated with pleiotropy, hitchhiking and genome-wide regulatory disruption which feminises flatwing male pheromones. The footprint of recent adaptive trait loss illustrates R. A. Fisher's influential prediction that variants with large mutational effect sizes can invade genomes during the earliest stages of adaptation to extreme pressures, despite having severely disruptive genomic consequences.

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