GEO DataSets

(Submitter supplied) Reciprocal deletion and duplication of 16p11.2 is the most common copy number variation (CNV) associated with Autism Spectrum Disorder (ASD) and other developmental disorders, and has significant effect on brain size. We used cortical organoids derived from ASD cases to investigate neurodevelopmental pathways dysregulated by dosage changes of 16p11.2 CNV. We show that organoids recapitulate patients’ macrocephaly and microcephaly phenotypes. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

108 Samples

Download data: XLSX

(Submitter supplied) Chromosome 16p11.2 reciprocal genomic disorder due to recurrent copy number variants (CNVs) involves intellectual disability, autism spectrum disorder (ASD), and schizophrenia but the responsible mechanisms are not known. To systemically dissect molecular effects, we performed transcriptome profiling of 350 libraries from six tissues (cortex, cerebellum, striatum, liver, brown fat, white fat) in mouse models harboring CNVs of the syntenic 7qF3 region, as well as cellular, transcriptional, and single-cell analyses in 54 isogenic neural stem cell, induced neuron, and cerebral organoid models of CRISPR-engineered 16p11.2 CNVs. more...

Organism:

Mus musculus; Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL24676 GPL13112 GPL16791

415 Samples

Download data: TXT

(Submitter supplied) The 600kb BP4-BP5 16p11.2 CNV (copy number variant) is associated with neuroanatomical, neurocognitive and metabolic disorders. These recurrent rearrangements are associated with reciprocal phenotypes such as obesity and underweight, macro- and microcephaly, as well as autism spectrum disorder (ASD) and schizophrenia. Here we interrogated the transcriptome of individuals carrying reciprocal CNVs in 16p11.2. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL13158

99 Samples

Download data: CEL

(Submitter supplied) Autism spectrum disorder (ASD) is a common and etiologically heterogeneous neurodevelopmental disorder. Although many genetic causes have been identified (>200 ASD-risk genes), no single gene mutation accounts for >1% of all ASD cases. A role for epigenetic mechanisms in ASD etiology is supported by the fact that many ASD-risk genes function as epigenetic regulators and evidence that epigenetic dysregulation can interrupt normal brain development. more...

Organism:

Homo sapiens

Type:

Methylation profiling by genome tiling array

Platform:

GPL13534

134 Samples

Download data: IDAT

(Submitter supplied) Recurrent Copy Number Variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Dataset:

GDS4430

Platform:

GPL6246

37 Samples

Download data: CEL

Analysis of brain regions of C57BL/6N:129Sv animals harboring a df/+ deletion or dp/+ duplication in the chromosomal region corresponding to 16p11.2 in humans. Recurrent copy number variations (CNVs) of human 16p11.2 are associated with a variety of developmental/neurocognitive syndromes.

Organism:

Mus musculus

Type:

Expression profiling by array, transformed count, 3 genotype/variation, 8 individual, 4 tissue sets

Platform:

GPL6246

Series:

GSE32012

37 Samples

Download data: CEL

(Submitter supplied) We report two bulk transcriptomic datasets of striatum from male and female mice carrying either the 16p11.2 hemideletion of 3 genes hemideletion knockout within this region.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24247

58 Samples

Download data: TXT

(Submitter supplied) Microdeletions and microduplications of the 16p11.2 chromosomal locus are implicated in a collection of neurodevelopmental disorders and reciprocal physiological conditions such as macro/microcephaly and high/low body mass index. To facilitate cellular and molecular investigations of these phenotypes, we generated 65 clones of human induced pluripotent stem cells (hiPSCs) from 13 individuals with 16p11.2 copy number variations (CNVs) and made each clone available by request from the Simons Foundation Autism Research Initiative (SFARI). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

52 Samples

Download data: CSV

(Submitter supplied) Understanding evolutionary mechanisms underlying expansion and reorganization of the human brain represents an important aspect in analyzing the emergence of cognitive abilities typical of our species. Comparative analyses of neuronal phenotypes in closest living relatives (Pan troglodytes; the common chimpanzee) can shed the light into changes in neuronal morphology compared to the last common ancestor (LCA), opening possibilities for analyses of the timing of their appearance, and the role of evolutionary mechanisms favoring a particular type of information processing in humans. more...

Organism:

Pan troglodytes; Homo sapiens

Type:

Expression profiling by high throughput sequencing

4 related Platforms

12 Samples

Download data: TXT

(Submitter supplied) Understanding cellular and molecular differences between human and non-human primates (NHPs) is essential to the basic comprehension of the evolution and diversity of our own species. Until now, preserved tissues have been the main source of most comparative studies between humans, chimpanzees (Pan troglodytes) and bonobos (Pan paniscus). However, these tissue samples do not fairly represent the distinctive traits of live cell behavior, are not amenable to genetic manipulation and do not allow translation of observed differences into phenotypical divergence. more...

Organism:

Pan troglodytes; Pan paniscus; Homo sapiens

Type:

Expression profiling by high throughput sequencing; Non-coding RNA profiling by high throughput sequencing

Platforms:

GPL16809 GPL11154 GPL17238

18 Samples

Download data: TXT

(Submitter supplied) To investigate the cell types and driver genes perturbed by 16p11.2 deletions using cerebral organoids

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20795

71 Samples

Download data: XLSX

(Submitter supplied) As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identify a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. more...

Organism:

Drosophila melanogaster

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13304

21 Samples

Download data: TXT

(Submitter supplied) E3-ubiquitin ligase Cullin3 (Cul3) is a high confidence risk gene for Neurodevelopmental Disorders such as Autism Spectrum Disorder (ASD) and Developmental Delay (DD). This study identifies the impact of the ASD-associated de novo Cul3-mutation on brain anatomy, behavior, molecular, cellular, and circuit-level mechanisms during early neocortical development. We report that Cul3 mutant mice have microcephaly and severe brain structure defects. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

108 Samples

Download data: TXT

(Submitter supplied) Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). Many ASD risk genes have been identified as critical for brain development, but the contribution of genetic backgrounds, although inferred in complex genetic disorders such as ASD, remains unclear. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygous PTEN p.I135L mutation found in an ASD patient with macrocephaly dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

18 Samples

Download data: TSV

(Submitter supplied) Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). Many ASD risk genes have been identified as critical for brain development, but the contribution of genetic backgrounds, although inferred in complex genetic disorders such as ASD, remains unclear. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygous PTEN p.I135L mutation found in an ASD patient with macrocephaly dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: H5

(Submitter supplied) Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). Many ASD risk genes have been identified as critical for brain development, but the contribution of genetic backgrounds, although inferred in complex genetic disorders such as ASD, remains unclear. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygous PTEN p.I135L mutation found in an ASD patient with macrocephaly dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

12 Samples

Download data: H5

(Submitter supplied) Alterations in cortical neurogenesis are implicated in neurodevelopmental disorders including autism spectrum disorders (ASDs). Many ASD risk genes have been identified as critical for brain development, but the contribution of genetic backgrounds, although inferred in complex genetic disorders such as ASD, remains unclear. Here, using isogenic induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) and cortical organoid models, we report that a heterozygous PTEN p.I135L mutation found in an ASD patient with macrocephaly dysregulates cortical neurogenesis in an ASD genetic background-dependent fashion. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

54 Samples

Download data: TSV

(Submitter supplied) The mechanisms by which genomic risks contribute to the onset of neuropsychiatric conditions remain a key challenge and a prerequisite for successful development of effective therapies. 15q11.2 copy number variation (CNV) containing the CYFIP1 gene is associated with autism and schizophrenia. Using stem cell models, we show that 15q11.2 deletion (15q11.2del) and CYFIP1 loss of function (CYFIP1-LoF) lead to premature neuronal differentiation, while CYFIP1 gain of function (CYFIP1-GoF) favors neural progenitor maintenance. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

71 Samples

Download data: TXT

(Submitter supplied) Background ­- Schizophrenia (SCZ) is a debilitating psychiatric disorder with a large genetic contribution; however, its neurodevelopmental substrates remain largely unknown. Modeling pathogenic processes in SCZ using human iPSC-derived neurons (iNs) has emerged as a promising strategy. Copy number variations (CNV) confer high genetic risk for SCZ, with duplication of the 16p11.2 locus increasing risk 14.5 fold. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

23 Samples

Download data: CSV, XLSX

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Rattus norvegicus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL22396

39 Samples

Download data: TXT