The haplo-spliceo-transcriptome of the human Major Histocompatibility Complex
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Claire Vandiedonck
PROVIDER: E-GEOD-22455 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This experiment accompanies the main analysis using a custom MHC array to define the first high-resolution, strand-specific transcriptional map of the MHC, defining differences in gene expression for three common haplotypes associated with autoimmune disease. Unstimulated samples for each haplotype were hybridised to Affymetrix Human Exon 1.0 ST arrays as well the custom MHC array. Exon array data were used to assess the concordance of signal obtained from the two platforms and to investigate the extent of alternative splicing in the MHC, and how it compares to the rest of the genome. Lymphoblastoid cell lines carrying three common autoimmunity haplotypes (COX, PGF, QBL) were analysed in triplicate using the Affymetrix Human Exon 1.0 ST Array.
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Project description:The human MHC is a paradigm for genomics, showing striking association with disease but functional variants remain largely unresolved. Using an original hybrid microarray (containing tiling and junction probes) for the MHC and accounting for known sequence diversity, we have drawn the first high-resolution, strand-specific transcriptional map of the MHC, defining differences in gene expression for three common haplotypes associated with autoimmune disease. In total, 6% of the MHC is transcribed with one transcript per 1.4kb, including previously unrecognized intergenic transcription. The distributions of differentially expressed probes and polymorphisms between haplotypes are significantly correlated, arguing for cis effects. Haplotype-specific transcription involved 96 differentially expressed genes, including ZFP57, which was validated in a cohort of healthy volunteers, while 526 exons show haplotypic differences. We also find splicing events are significantly more extensive in the MHC than in the rest of the genome. This study marks a new step in immunogenetics. The results files (.wig and .gff) contain tiling data for both the shared-path and the alternate paths (shared and haplotype-specific) , defining transcriptional activity across the entire MHC region in each sample. Lymphoblastoid cell lines carrying three common autoimmunity haplotypes (COX, PGF, QBL) were analysed in triplicate using the custom MHC array, under both unstimulated and stimulated (200nM PMA and 125nM ionomycin for 6 hours) conditions.
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Project description:The study pursued dual goals: To advance mRNA-seq bioinformatics towards unbiased transcriptome capture and to demonstrate its potential for discovery in neuroscience by applying the approach to an in vivo model of neurological disease. We found that 12.4% of known genes were induced and 7% were suppressed in the dysfunctional (but anatomically intact) L4 dorsal root ganglion (DRG) 2 weeks after L5 spinal Nerve Ligation (SNL). A new algorithm for agnostic mapping of pre-mRNA splice junctions (SJ) achieved a precision of 97%. mRNA-seq of L4 DRG 2 weeks and 2 months after L5 spinal nerve ligation. CONTROL and SNL were used to identify differential gene expression between chronic pain and standard conditions in Rattus norvegicus. CONTROL and SNL and PILOT were used to perform 'agnostic splice site discovery' in the nervous system transcriptome in Rattus norvegicus
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