Table 5.
Overview of studies using the ATP/Autism BrainNet collection
| Reference | Bio-collection | Samples | Number | Study | Findings |
|---|---|---|---|---|---|
| [337] | ATP and AGRE | Brain tissue, blood and lymphoblasts | 18 subjects (ATP) 841 families (AGRE) 1029 families (total) |
Gene expression and association analysis | Altered expression of mitochondrial genes in anterior cingulate gyrus, motor cortex and thalamus of ASD patients. Polymorphisms in MTX2, NEFL and SLC25A27 found to be associated with ASD. |
| [338] | ATP | Brain tissue | 18 subjects | Gene expression analysis | Reduced expression of several genes related to electron transport in anterior cingulate gyrus, motor cortex and thalamus of ASD patients |
| [339] | ATP | Brain tissue | 57 subjects | Functional genomic study | Analysis of CNVs showed differences of what pathways are altered between children and adults; cell number, cortical patterning and differentiation in the former, and signalling and repair pathways in the latter. Prefrontal cortex samples were used |
| [106] | ATP | Brain tissue | 33 subjects | GWAS | Patients with ASD had more genes that were up- or down-regulated in an- individual specific manner when prefrontal cortex tissue was examined |
| [340] | ATP | Brain tissue | 126 subjects (total) 42 subjects (ATP) |
Sequencing study | Recurrent deleterious mutations found in ARID1B, SCN1A, SCN2A and SETD2. Higher proportion of mutations that are deleterious, protein-altering or cause loss-of-function in ASD patients compared to controls. Cortical and cerebellar tissue was used. |
| [107] | ATP | Brain tissue | 25 subjects | Deep sequencing study | Altered adenosine to inosine editing found in cerebella tissue from ASD patients. Dysfunctional for of editing enzyme ADARB1 more frequently in ASD Cerebella |
| [341] | ATP | Brain tissue | 28 subjects (ATP) 43 subjects (total) |
Gene expression analysis | Signalling partners of FMRP and GRM5 (HOMER1, APP, RAC1, STEP) shown to have altered expression in the cerebellar vermis and superior frontal cortex in ASD patients compared to controls. |
| [342] | ATP | Brain tissue | 19 subjects | mRNA analysis | Reduction of multiple GABA receptor subtypes (A6, B2, D, E, G2, T and P2) detected in cerebella vermis and superior frontal cortex ASD patients |
| [343] | ATP | Brain tissue | 25 subjects | Assay study | Imbalance in isoforms of precursor BDNF protein found in fusiform gryrus of ASD patients |
| [103] | ATP | Brain tissue | 18 subjects | Transcriptional and epigenetic association analysis | Downregulation of genes related to oxidative phosphorylation and protein translation. Associations were found between specific behaviour domains of ASD and gene expression modules related to myelination, immune response and purinergic signalling. Cerebral and Brodmann area 19 tissue was used |
| [108] | ATP | Brain tissue | 16 subjects | Methylation study | Increased methylation was found for the gene OTXR in ASD patients in blood and DNA from the temporal cortex |
| [104] | ATP | Brain tissue | 107 subjects | Transcriptome analysis | Dysregulated gene expression associated with glial cells shown to have negative correlation with gene expression relating to synaptic transmission in ASD patients when Brodmann areas 10, 19 and 44 were analysed |
| [344] | ATP | Brain tissue | 32 subjects | Transcription analysis | RORA may have dimorphic effects on gene expression in certain areas of cortical tissue between genders, and deficiency appears to cause greater gene dysregulation amongst males in both mice and humans |
| [345] | ATP | Brain tissue | 30 subjects | Transcription analysis | RPP25 expression is decreased in the prefrontal cortex of ASD patients |
| [116] | ATP | Brain tissue | 23 subjects | Alternate splicing analysis and discovery | A conserved group of microexons involved in modulation of interaction domains of proteins and neurogenesis is disrupted in patients with ASD |
| [29] | ATP | Brain tissue | 17 subjects | Methylation study | UBE3 implicated as a contributing gene to autism and Angelman syndrome |
| [346] | ATP | Brain tissue | 20 subjects | Anti-sense RNA study | Discovery of anti-sense non-coding RNA that binds to moesin at 5p14.1 in ASD cerebral cortex tissue |
| [109] | ATP | Brain tissue | 40 subjects | Methylation study | 4 differentially methylated regions; 3 in temporal cortex and 1 in cerebellum. 3/4 regions were again found in different samples and brain regions. |
| [117] | ATP | Brain tissue and lymphoblasts | 36 subjects (total) | Transcription and alternative splicing study | Accelerated decrease of MS gene transcription across ageing found in ASD patient cerebral cortex samples |
| [347] | ATP | Brain tissue | 73 subjects | Methylation study | Correlation found between reduced expression of MECP2 and increased methylation on the promoter region |
| [110] | ATP | Brain tissue | 24 subjects | Methylation study | Hypomethylation of mir142 and upregulation of mi-RNAs targeting OXTR gene in prefrontal cortex of ASD brains |
| [348] | ATP | Brain tissue | 24 subjects | Signal transduction study | Downregulation of PI3K-Akt genes observed in fusiform gyrus tissue of ASD patients. Similar effects noted in rat brain tissue exposed to valproic acid |
| [349] | ATP | Brain tissue (ATP) neuronal cells |
6 subjects | CHiP study |
RORA found to regulate 2BP1, CYP19A1, HSD17B10, ITPR1, NLGN1 and NTRK2 via transcription. Low levels of RORA causes dysregulation of these genes and associated pathways. Prefrontal cortex and cerebellum tissue was used. |
| [350] | ATP | Brain tissue (ATP) | 153 families (other) 54 subjects (ATP) |
Functional characterisation study | Variant of the HTR2A gene rs6311 in ASD patients has lower level of expression and contains extended 5′untranslated region. Speculation that this variant could be a risk factor in ASD. Frontopolar cortex tissue was used. |
| [351] | ATP | Brain tissue | 28 subjects | Micro-RNA study | Difference in pattern of micro-RNA expression between ASD superior temporal gyrus samples and controls. Further evidence that Mir-320, Mir-132 and Mir-302 are involved in ASD. |
| [113] | ATP | Brain tissue | 94 subjects (total) 51 subjects (ATP) |
Acetylome study | Common acetylome signatures found amongst 68% of ASD cases in 5000 regulatory regions in the prefrontal and temporal cortex. Acetylome profiles were not affected by SNPs at these regulatory regions. |
| [352] | ATP and AGRE | Brain tissue, blood and lymphoblasts | 21 subjects (ATP) 252 families (AGRE) |
Association study | Variants of LMX1B show modest association with ASD. Analysis of mRNA from anterior cingulate gyrus is much lower in ASD patients compared to controls. |
| [105] | ATP | Brain tissue | 36 subjects | Gene co-expression network analysis | Transcriptional and splicing dysfunction implicated in disorder. Enrichment for genes in glial, immune and neuronal modules. Gene A2BP1 linked to alterations in splicing. Studies based on using temporal cortex, frontal cortex and cerebellum |
| [353] | ATP | Brain tissue | 28 subjects (total) 8 subjects (ATP) |
Gene expression analysis | Genes expressed at higher levels in males enriched in upregulated genes in post-mortem neocortical tissue in ASD patients, including astrocyte and microglia markers |
| [118] | ATP | Brain tissue (ATP) and placenta |
12 subjects (ATP) 64 subjects (total) |
Vitamin B12 study | Reduced levels of B12 found in ASD, aged and Schizophrenic patients compared to controls. oxidative stress found in ASD and Schizophrenia patients. Frontal cortex tissue was used |
| [114] | ATP | Brain tissue | 98 subjects | Methylation study | Altered methylation patterns discovered in SHANK3 gene in cerebella tissue of ASD patients |
| [115] | ATP | Brain tissue | 20 subjects | Epigenetic study | Enrichment of 5-hmc in cerebella tissue may be associated with increased binding by MECP2 to RELN and GAD1 promotors |
Study numbers listed as families or subjects wherever applicable