Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

MRNA-Seq Expression profiling of human post-mortem BA9 brain tissue for Huntington's Disease and neurologically normal individuals


ABSTRACT: Huntington’s Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR<0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD. 20 Huntington's Disease and 49 neurologically normal control samples from post-mortem human subjects

ORGANISM(S): Homo sapiens

SUBMITTER: Richard Myers 

PROVIDER: E-GEOD-64810 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression.

Labadorf Adam A   Hoss Andrew G AG   Lagomarsino Valentina V   Latourelle Jeanne C JC   Hadzi Tiffany C TC   Bregu Joli J   MacDonald Marcy E ME   Gusella James F JF   Chen Jiang-Fan JF   Akbarian Schahram S   Weng Zhiping Z   Myers Richard H RH  

PloS one 20151204 12


Huntington's Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently  ...[more]

Similar Datasets

2016-08-19 | E-GEOD-84665 | biostudies-arrayexpress
2015-03-12 | E-GEOD-64977 | biostudies-arrayexpress
2015-04-28 | E-GEOD-65996 | biostudies-arrayexpress
2014-03-07 | E-GEOD-52514 | biostudies-arrayexpress
2012-02-17 | E-GEOD-34854 | biostudies-arrayexpress
2015-08-10 | E-GEOD-71299 | biostudies-arrayexpress
2016-01-15 | E-GEOD-68719 | biostudies-arrayexpress
2012-12-01 | E-GEOD-34179 | biostudies-arrayexpress
2016-03-01 | E-GEOD-72808 | biostudies-arrayexpress
2015-12-08 | GSE64810 | GEO