Brain Transcriptional and Epigenetic Associations with Autism
Publication Date
September 12, 2012
Journal
PLOS ONE
Authors
Matthew R. Ginsberg, Robert A. Rubin, Tatiana Falcone, Angela H. Ting, et al
Volume
7
Issue
9
Pages
e44736
DOI
https://dx.plos.org/10.1371/journal.pone.0044736
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0044736
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22984548
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440365
Europe PMC
http://europepmc.org/abstract/MED/22984548
Web of Science
000308738500077
Scopus
84866309634
Mendeley
http://www.mendeley.com/research/brain-transcriptional-epigenetic-associations-autism
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Mendeley | Further Information

{"title"=>"Brain Transcriptional and Epigenetic Associations with Autism", "type"=>"journal", "authors"=>[{"first_name"=>"Matthew R.", "last_name"=>"Ginsberg", "scopus_author_id"=>"55359726900"}, {"first_name"=>"Robert A.", "last_name"=>"Rubin", "scopus_author_id"=>"55788564600"}, {"first_name"=>"Tatiana", "last_name"=>"Falcone", "scopus_author_id"=>"7006288452"}, {"first_name"=>"Angela H.", "last_name"=>"Ting", "scopus_author_id"=>"7102858524"}, {"first_name"=>"Marvin R.", "last_name"=>"Natowicz", "scopus_author_id"=>"7006406023"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84866309634", "sgr"=>"84866309634", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0044736", "pmid"=>"22984548", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"365652620"}, "id"=>"9ea5c31a-a242-3bd1-8276-953d73c1cd7a", "abstract"=>"BACKGROUND Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. METHODOLOGY/PRINCIPAL FINDINGS To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. CONCLUSIONS/SIGNIFICANCE This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.", "link"=>"http://www.mendeley.com/research/brain-transcriptional-epigenetic-associations-autism", "reader_count"=>136, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>9, "Student > Doctoral Student"=>11, "Researcher"=>28, "Student > Ph. D. Student"=>31, "Student > Postgraduate"=>6, "Student > Master"=>21, "Other"=>4, "Student > Bachelor"=>12, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>9, "Student > Doctoral Student"=>11, "Researcher"=>28, "Student > Ph. D. Student"=>31, "Student > Postgraduate"=>6, "Student > Master"=>21, "Other"=>4, "Student > Bachelor"=>12, "Lecturer"=>3, "Lecturer > Senior Lecturer"=>1, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>7, "Agricultural and Biological Sciences"=>46, "Chemistry"=>1, "Computer Science"=>2, "Engineering"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>17, "Nursing and Health Professions"=>3, "Medicine and Dentistry"=>27, "Neuroscience"=>14, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Psychology"=>8, "Social Sciences"=>6}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>27}, "Social Sciences"=>{"Social Sciences"=>6}, "Psychology"=>{"Psychology"=>8}, "Unspecified"=>{"Unspecified"=>7}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Neuroscience"=>{"Neuroscience"=>14}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>46}, "Computer Science"=>{"Computer Science"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>17}}, "reader_count_by_country"=>{"Netherlands"=>1, "Korea (South)"=>1, "United States"=>6, "Brazil"=>1, "India"=>1}, "group_count"=>3}

CrossRef

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/305274", "https://ndownloader.figshare.com/files/305333", "https://ndownloader.figshare.com/files/305383", "https://ndownloader.figshare.com/files/305413", "https://ndownloader.figshare.com/files/305449", "https://ndownloader.figshare.com/files/305501", "https://ndownloader.figshare.com/files/305567", "https://ndownloader.figshare.com/files/305628", "https://ndownloader.figshare.com/files/305690", "https://ndownloader.figshare.com/files/305745", "https://ndownloader.figshare.com/files/305805", "https://ndownloader.figshare.com/files/305863", "https://ndownloader.figshare.com/files/305917"], "description"=>"<div><h3>Background</h3><p>Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic.</p> <h3>Methodology/Principal Findings</h3><p>To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling.</p> <h3>Conclusions/Significance</h3><p>This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.</p> </div>", "links"=>[], "tags"=>["transcriptional", "epigenetic", "associations", "autism"], "article_id"=>120225, "categories"=>["Biological Sciences", "Cell Biology", "Neuroscience", "Genetics"], "users"=>["Matthew R. Ginsberg", "Robert A. Rubin", "Tatiana Falcone", "Angela H. Ting", "Marvin R. Natowicz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0044736.s001", "https://dx.doi.org/10.1371/journal.pone.0044736.s002", "https://dx.doi.org/10.1371/journal.pone.0044736.s003", "https://dx.doi.org/10.1371/journal.pone.0044736.s004", "https://dx.doi.org/10.1371/journal.pone.0044736.s005", "https://dx.doi.org/10.1371/journal.pone.0044736.s006", "https://dx.doi.org/10.1371/journal.pone.0044736.s007", "https://dx.doi.org/10.1371/journal.pone.0044736.s008", "https://dx.doi.org/10.1371/journal.pone.0044736.s009", "https://dx.doi.org/10.1371/journal.pone.0044736.s010", "https://dx.doi.org/10.1371/journal.pone.0044736.s011", "https://dx.doi.org/10.1371/journal.pone.0044736.s012", "https://dx.doi.org/10.1371/journal.pone.0044736.s013"], "stats"=>{"downloads"=>8, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Brain_Transcriptional_and_Epigenetic_Associations_with_Autism/120225", "title"=>"Brain Transcriptional and Epigenetic Associations with Autism", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-09-12 00:03:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/578025"], "description"=>"<p>(<b>A</b>) Heatmap of module-variable associations for cerebellar hemisphere samples from weighted genome co-expression network analysis, including domain scores for the ADI-R. Cells are color-coded by correlation coefficient and * is placed in cells having associations with p-values ≤0.01. Autism, dichotomous variable autism vs control; PMI, postmortem interval; A, ADI-R Social interaction impairments domain; B, ADI-R Communication and language impairments domain; C, ADI-R Repetitive and stereotyped behaviors domain. (<b>B</b>) Gene ontology enrichment annotation clusters for the three significant gene modules associated with specific ADI-R domain scores. P, p-value; r, Pearson correlation coefficient.</p>", "links"=>[], "tags"=>["domains", "autism", "diagnostic", "interview-revised"], "article_id"=>248513, "categories"=>["Biological Sciences", "Cell Biology", "Neuroscience", "Genetics"], "users"=>["Matthew R. Ginsberg", "Robert A. Rubin", "Tatiana Falcone", "Angela H. Ting", "Marvin R. Natowicz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044736.g002", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Specific_domains_of_the_Autism_Diagnostic_Interview_Revised_ADI_R_are_associated_with_specific_gene_modules_/248513", "title"=>"Specific domains of the Autism Diagnostic Interview-Revised (ADI-R) are associated with specific gene modules.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-12 02:21:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/578150"], "description"=>"<p>(<b>A</b>) Unsupervised correspondence analysis of genome-wide CpG methylation in control and autism cerebellar cortex and BA19 cerebral cortex demonstrates that brain region and age are associated with the largest two sources of variability, respectively, in the data. The first two principal components are listed on the x- and y-axis respectively, with percent of variance explained in parentheses. Bubbles correspond to individual samples with area proportional to age of subject, bubble outline to region, and color to phenotype. (<b>B</b>) Percent of genome-wide methylated probes in cerebellar cortex or BA19 cortex in control and autism samples. Error bars represent standard deviations. There was no significant difference in global methylation between autism vs control cerebellum or BA19 cortex. There was a significant difference between brain regions, as expected (alpha = 0.05; Wilcoxon rank-sum test). (<b>C</b>) Pyrosequencing of bisulfite-treated DNA. Percent methylation at individual CpG dinucleotides is reported in cerebellar cortex samples (n ≥7 per group) for <i>a priori</i> candidate genes suspected to exhibit differential methylation. X-axis represents locus relative to transcription start site. Error bars represent standard deviations.</p>", "links"=>[], "tags"=>["differential", "methylation", "genomic", "dna", "was", "autism", "cerebellar", "cortex", "ba19"], "article_id"=>248636, "categories"=>["Biological Sciences", "Cell Biology", "Neuroscience", "Genetics"], "users"=>["Matthew R. Ginsberg", "Robert A. Rubin", "Tatiana Falcone", "Angela H. Ting", "Marvin R. Natowicz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044736.g003", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_No_differential_methylation_of_genomic_DNA_was_identified_between_control_and_autism_cerebellar_cortex_or_BA19_cortex_/248636", "title"=>"No differential methylation of genomic DNA was identified between control and autism cerebellar cortex or BA19 cortex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-12 02:23:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/577919"], "description"=>"<p>(<b>A</b>) Unsupervised correspondence analysis of whole-genome transcriptome expression data demonstrates that brain region is associated with the greatest source of variability in the data. The second principal component is associated with variability mostly among autistic samples. The first two principal components are listed on the x- and y-axis respectively, with percent of variance explained in parentheses. Bubbles represent individual samples, with area proportional to age, outline to brain region, and color to phenotype. (<b>B</b>) Heatmap of the top 50 differentially expressed probes between autistic and control brain, accounting for brain region, separates most autistic brains from controls (FDR ≤5%). Rows correspond to probes and columns to samples. The dendrogram represents sample similarity on the basis of the top 50 differentially expressed probes. Probes with log<sub>2</sub>-fold change >0.7 are listed in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0044736#pone.0044736.s007\" target=\"_blank\">table S3</a>. (<b>C</b>) The top 300 differentially expressed probes are enriched for gene ontology annotation clusters corresponding to mitochondrial oxidative phosphorylation and protein translation. ADI-R, Autism Diagnostic Interview-Revised; BA19, Brodmann area 19; CER, cerebellum; PMI, postmortem interval.</p>", "links"=>[], "tags"=>["shows", "transcriptional", "heterogeneity", "differential", "genes", "mitochondrial", "oxidative", "phosphorylation"], "article_id"=>248401, "categories"=>["Biological Sciences", "Cell Biology", "Neuroscience", "Genetics"], "users"=>["Matthew R. Ginsberg", "Robert A. Rubin", "Tatiana Falcone", "Angela H. Ting", "Marvin R. Natowicz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0044736.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Autistic_brain_shows_transcriptional_heterogeneity_and_differential_expression_of_genes_of_mitochondrial_oxidative_phosphorylation_and_protein_translation_/248401", "title"=>"Autistic brain shows transcriptional heterogeneity and differential expression of genes of mitochondrial oxidative phosphorylation and protein translation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-09-12 02:20:01"}

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Relative Metric

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