, 2008; Wendelken et al , 2011), has a protracted course of devel

, 2008; Wendelken et al., 2011), has a protracted course of development extending into adolescence and beyond (Dumontheil et al., 2008; Rakic and Yakovlev, 1968; Wendelken et al., 2011), and appears to be affected in diseases that affect higher-order cognition, including autism and schizophrenia (see the review of Dumontheil et al., 2008). We find

many more expression changes using NGS than with microarrays and use network biology to put the changes observed into a systems-level context, showing high conservation of the caudate transcriptome, while identifying eight human-specific gene coexpression modules in frontal cortex. Moreover, Imatinib cost we discover gene coexpression signatures related to either neuronal processes or neuropsychiatric diseases, in addition to a human-specific frontal pole module that has CLOCK as its hub and includes several psychiatric disease genes. selleck products Another frontal lobe module that underwent changes in splicing regulation on the human lineage is enriched for neuronal

morphological processes and contains genes coexpressed with FOXP2, a gene important for speech and language. By using NGS, by including an outgroup, and by surveying several brain regions, these findings highlight and prioritize the human-specific gene expression patterns that may be most relevant for human brain evolution. At least four individuals from each species and each brain region were assessed (see Table S1 available online) using DGE-based sequencing and two different microarray platforms, Affymetrix (AFX) and Illumina (ILM) (Figure 1). The total number of unique genes available

for analysis among the species was 16,813 for DGE, 12,278 for Illumina arrays, and 21,285 for Affymetrix arrays (Figure 1). Analysis of DGE data revealed an average of 50% human, 43% chimp, and 39% macaque DGE reads mapping to its respective genome, with two to three million total reads mapping on average (Table S1); pairwise analysis of DGE samples revealed high correlations (Table S1). Neither the total number of reads nor the total number of mapped reads were significantly different among species for a given region, eliminating these as potential confounders in cross-species comparisons (total reads: FP, p = 0.993; CN, p = 0.256; HP, p = 0.123; uniquely mapped reads: Ribonucleotide reductase FP, p = 0.906; CN, p = 0.216; HP, p = 0.069; ANOVA). The samples were primarily segregated based on species and brain region using hierarchical clustering (data not shown). We also conducted thorough outlier analysis as well as covariate analysis and do not find that factors such as postmortem interval, sex, RNA extraction, library preparation date, sequencing slide, or sequencing run are significant sample covariates (see Supplemental Experimental Procedures). On average, DGE identified 25%–60% more expressed genes in the brain than either microarray platform (Figures S1A and S1B).

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