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Data Set Group: Brain, Development (Yale/Sestan) Affy Hu-Exon 1.0 ST (Jul11) modify this page

Data Set: Human Primary Auditory (A1) Cortex Affy Hu-Exon 1.0 ST (Jul11) Quantile modify this page
GN Accession: GN329
GEO Series: GSE13344
Title: Exon Array expression data from 13 areas of the late second trimester human brain
Organism: Human (hg19)
Group: HSB
Tissue: Primary Auditory (A1) Cortex mRNA
Dataset Status: Public
Platforms: Affy Human Exon 1.0 ST Array
Normalization: QUANT
Contact Information
Matthew B. Johnson
Yale School of Medicine
333 Cedar Street, SHM C-338C
New Haven, CT 6510 USA
Tel. 203-737-1435
sestanlab@yale.edu
Website
Download datasets and supplementary data files

Specifics of this Data Set:
None

Summary:

Our understanding of the evolution, formation, and pathological disruption of human brain circuits is impeded by a lack of comprehensive data on the developing brain transcriptome. Thus, we have undertaken whole-genome, exon-level expression analysis of thirteen regions from left and right sides of the mid-fetal human brain, finding 76% of genes to be expressed, and 44% of these to be differentially regulated. These data reveal a large number of specific gene expression and alternative splicing patterns, as well as co-expression networks, associated with distinct regions and neurodevelopmental processes. Of particular relevance to cognitive specializations, we have characterized the transcriptional landscapes of prefrontal cortex and perisylvian speech and language areas, which exhibit a population-level global expression symmetry. Finally, we show that differentially expressed genes are more frequently associated with human-specific evolution of putative cis-regulatory elements. Altogether, these data provide a wealth of novel biological insights into the complex transcriptional and molecular underpinnings of human brain development and evolution.



About the cases used to generate this set of data:

RNA was isolated from 13 brain regions, from both hemispheres, of four late mid-fetal human brains, with a total PMI of less than one hour, and hybridized to Affymetrix Human Exon 1.0 ST arrays. Affymetrix CEL files were imported into Partek GS using Robust Multichip Average (RMA) background correction, quantile normalization, and GC content correction. The normalized data were then converted to log-ratios, relative to arrays hybridized with RNA pooled from all regions of the same brain. Signal log-ratios are displayed here as green for negative (underexpression) and red for positive (overexpression).

Table 1 | Periods of human development and adulthood as defined in this study.

Period Description Age
1 Embryonic 4≤ Age <8 Postconceptual weeks (PCW)
2 Early fetal 8≤ Age <10 PCW
3 Early fetal 10≤ Age <13 PCW
4 Early midfetal 13≤ Age <16 PCW
5 Early midfetal 16≤ Age <19 PCW
6 Late midfetal 19≤ Age <24 PCW
7 Late fetal 24≤ Age <38 PCW
8 Neonatal and early infancy Birth≤ Age <6 Postnatal months (M)
9 Late infancy 6 M≤ Age <12 M
10 Early childhood 1≤ Age <6 Postnatal years (Y)
11 Middle and late childhood 6≤ Age <12 Y
12 Adolescence 12≤ Age <20 Y
13 Young adulthood 20≤ Age <40 Y
14 Middle adulthood 40≤ Age <60 Y
15 Late adulthood 60 Y ≤ Age


About the tissue used to generate this set of data:

Tissue was microdissected from 13 regions, including 9 distinct neocortical areas, from both left and right sides of four late second trimester human brain specimens. Gene- and exon-level differential expression analyses were performed by mixed model, nested analysis of variance using the XRAY software from Biotique Systems. Further details available in Johnson, Kawasawa, et al., "Functional and Evolutionary Insights into Human Brain Development through Global Transcriptome Analysis" Neuron, Volume 62, Issue 4, 2009.

Ethnicity codes are as follows: AA = African American, A = ,  A/E =  X,  As,=  , H = , E = , CC =  and n/a= unknown

 

This track displays exon microarray expression data from the late mid-fetal human brain, generated by the Sestan Lab at Yale University. The data represent 13 brain regions, including nine areas of neocortex, and both hemispheres. By default, arrays are grouped by the median for each brain region, including each neocortical area. Alternatively, neocortex areas can be grouped together; arrays can be grouped by mean; or all 95 arrays can be shown individually.

Table 2 | Ontology and nomenclature of analyzed brain regions and neocortical areas.

Period 1 Period 2 Period 3 - 15
FC: Frontal cerebral wall FC OFC: Orbital prefrontal cortex
    DFC: Dorsolateral prefrontal cortex
    VFC: Ventrolateral prefrontal cortex
    MFC: Medial prefrontal cortex
    M1C: Primary motor (M1) cortex
PC: Parietal cerebral wall PC S1C: Primary somatosensory (S1) cortex
    IPC: Posterior inferior parietal cortex
TC: Temporal cerebral wall TC  A1C: Primary auditory (A1) cortex
    STC: Posterior superior temporal cortex
    ITC: Inferior temporal cortex
OC: Occipital cerebral wall OC V1C: Primary visual (V1) cortex
HIP: Hippocampal anlage HIP HIP: Hippocampus
    AMY: Amygdala
VF: Ventral forebrain CGE: Caudal ganglionic eminence STR: Striatum
  LGE: Lateral ganglionic eminence  
  MGE: Medial ganglionic eminence  
DIE: Diencephalon DTH: Dorsal thalamus MD: Mediodorsal nucleus of thalamus
URL: Upper (rostral) rhombic lip URL CBC: Cerebellar cortex


About the array platform:


About data values and data processing:

Normalized method: Quantile normalization. Partek Genomics Suite version 6.5 (Partek Incorporated, St. Louis, MO, USA) was used to normalize raw exon array data and to summarize expression of the probe set and transcript cluster. Affymetrix CEL files that passed QC analyses were imported into Partek Genomics Suite using the default Partek settings: RMA background correction114, quantile normalization, mean probe set summarization, and log2-transformation. Only high-quality core probe sets, as defined by Affymetrix, were included. 105,271 core probes (within 62,448 probe sets out of 230,918 core probe sets) contained SNPs defined in the probe group file HuEx-1_0-st-v2.r2-SNPs-Excluded.pgf provided by Affymetrix, which is based on the dbSNP database (version 129, April 2008) and SNPinprobe_1.0 database. we removed SNP-containing probe sets during the normalization step in the Partek program to be control for SNP-related confounding effects. The median of all individual probe sets of one transcript cluster was used as the estimate of gene expression values.



Notes:

The raw microarray data are available via the NCBI Gene Expression Omnibus. Data in GeneNetwork as of July 2015 are only gene-level data. We could also enter exon-level data on request.



Experiment Type:

Human Brain Specimens and Tissue Processing This study was carried out using post-mortem human brain specimens collected from the Human Fetal Tissue Repository at the Albert Einstein College of Medicine (AECOM). Dissected tissue was fresh-frozen in Trizol for RNA and DNA extraction, with a post-mortem interval of less than 1 hour. Remaining tissue was fixed and frozen, and sections were analyzed for neuropathological or developmental defects. Details of specimens, tissue processing, microdissection, and neuropathological assessment are given in the Supplemental Experimental Procedures and Table S1. These studies were approved by the Human Investigation Committees of AECOM and Yale University.

For initial analysis, all neocortex samples were grouped together. In subsequent analyses, neocortex areas were compared with each other. In most analyses reported, left and right side samples were treated as additional biological replicates.



Contributor:

Johnson MBKawasawa YISestan N



Citation:
  • Johnson MB, Kawasawa YI, Mason CE, Krsnik Z et al. Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron 2009 May 28;62(4):494-509. PMID: 19477152


Data source acknowledgment:


Study Id:
113

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