Dataset Information

Cytogenomic mapping and bioinformatic mining reveal interacting brain expressed genes for intellectual disability.

ABSTRACT: BACKGROUND:Microarray analysis has been used as the first-tier genetic testing to detect chromosomal imbalances and copy number variants (CNVs) for pediatric patients with intellectual and developmental disabilities (ID/DD). To further investigate the candidate genes and underlying dosage-sensitive mechanisms related to ID, cytogenomic mapping of critical regions and bioinformatic mining of candidate brain-expressed genes (BEGs) and their functional interactions were performed. Critical regions of chromosomal imbalances and pathogenic CNVs were mapped by subtracting known benign CNVs from the Databases of Genomic Variants (DGV) and extracting smallest overlap regions with cases from DatabasE of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER). BEGs from these critical regions were revealed by functional annotation using Database for Annotation, Visualization, and Integrated Discovery (DAVID) and by tissue expression pattern from Uniprot. Cross-region interrelations and functional networks of the BEGs were analyzed using Gene Relationships Across Implicated Loci (GRAIL) and Ingenuity Pathway Analysis (IPA). RESULTS:Of the 1,354 patients analyzed by oligonucleotide array comparative genomic hybridization (aCGH), pathogenic abnormalities were detected in 176 patients including genomic disorders in 66 patients (37.5%), subtelomeric rearrangements in 45 patients (25.6%), interstitial imbalances in 33 patients (18.8%), chromosomal structural rearrangements in 17 patients (9.7%) and aneuploidies in 15 patients (8.5%). Subtractive and extractive mapping defined 82 disjointed critical regions from the detected abnormalities. A total of 461 BEGs was generated from 73 disjointed critical regions. Enrichment of central nervous system specific genes in these regions was noted. The number of BEGs increased with the size of the regions. A list of 108 candidate BEGs with significant cross region interrelation was identified by GRAIL and five significant gene networks involving cell cycle, cell-to-cell signaling, cellular assembly, cell morphology, and gene expression regulations were denoted by IPA. CONCLUSIONS:These results characterized ID related cross-region interrelations and multiple networks of candidate BEGs from the detected genomic imbalances. Further experimental study of these BEGs and their interactions will lead to a better understanding of dosage-sensitive mechanisms and modifying effects of human mental development.

SUBMITTER: Xu F

PROVIDER: S-EPMC3905969 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cytogenomic mapping and bioinformatic mining reveal interacting brain expressed genes for intellectual disability.

Xu Fang F Li Lun L Schulz Vincent P VP Gallagher Patrick G PG Xiang Bixia B Zhao Hongyu H Li Peining P

Molecular cytogenetics 20140110 1

<h4>Background</h4>Microarray analysis has been used as the first-tier genetic testing to detect chromosomal imbalances and copy number variants (CNVs) for pediatric patients with intellectual and developmental disabilities (ID/DD). To further investigate the candidate genes and underlying dosage-sensitive mechanisms related to ID, cytogenomic mapping of critical regions and bioinformatic mining of candidate brain-expressed genes (BEGs) and their functional interactions were performed. Critical ...[more]

PMID: 24410907

Similar Datasets

Project description:Sleep has been strongly implicated in learning and especially in the reprocessing of recently acquired memory. Children with intellectual disability (ID) tend to have sleep-wake disturbances, which may contribute to the pathophysiology of the disease. As far as sleep is, in part, a circadian process, we decided to study rhythmic gene expression in hippocampus, a brain structure, which plays a key role in memory in human and rodents. By investigating the transcriptome of mouse adult hippocampus, we report here the identification of 663 circadian rhythm (CR)-regulated genes, which have been clustered in four categories, based on their temporal pattern of expression. In addition to the standard core-clock genes, enrichment analysis of the hippocampal CR-regulated genes revealed the presence of several transcription factors, underlying the existence of an inter-regulation of genes' expression between clusters. Interestingly, these hippocampal circadian rhythm-regulated genes are very enriched in sleep/wakefulness related genes. We show here that glucocorticoid signaling, already shown to be involved in memory regulation, is a circadian regulated pathway in hippocampus. Furthermore, we identified a list of 30 CR-regulated ID genes. Our results demonstrate that hippocampus can be considered as a peripheral oscillator and illustrate the link between circadian rhythm, sleep, intellectual disability and memory consolidation. In order to identify circadian rhythm-regulated genes in mouse hippocampus, we realized a study in dark-dark conditions, thus allowing to overcome the effects induced by light changes. To systematically identify genes with circadian regulated expression, RNA samples from the hippocampus of three mice at four Circadian Time (CT) points were used for expression profiling using Agilent microarray technology. The dark/dark period started at 7 p.m. The Circadian Time (CT) 18 samples were taken after 30 h of continuous dark; the other circadian times followed at 6-h intervals: CT0, CT6 and CT12 after 36, 42 and 48 h of continuous darkness, respectively.

Dataset Information

Cytogenomic mapping and bioinformatic mining reveal interacting brain expressed genes for intellectual disability.

Publications

Cytogenomic mapping and bioinformatic mining reveal interacting brain expressed genes for intellectual disability.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets