Previously published comparative functional genomic data sets from primates using frozen tissue samples, including many data sets from our own group, were often collected and analyzed using nonoptimal study designs and analysis approaches. In addition, when samples from multiple tissues were studied in a comparative framework, individuals and tissues were confounded. We designed a multitissue comparative study of gene expression and DNA methylation in primates that minimizes confounding effects by using a balanced design with respect to species, tissues, and individuals. We also developed a comparative analysis pipeline that minimizes biases attributable to sequence divergence. Thus, we present the most comprehensive catalog of similarities and differences in gene expression and DNA methylation levels between livers, kidneys, hearts, and lungs, in humans, chimpanzees, and rhesus macaques. We estimate that overall, interspecies and inter-tissue differences in gene expression levels can only modestly be accounted for by corresponding differences in promoter DNA methylation. However, the expression pattern of genes with conserved inter-tissue expression differences can be explained by corresponding interspecies methylation changes more often. Finally, we show that genes whose tissue-specific regulatory patterns are consistent with the action of natural selection are highly connected in both gene regulatory and protein-protein interaction networks.

Inter-individual variation in gene expression has been shown to be heritable and is often associated with differences in disease susceptibility between individuals. Many studies focused on mapping associations between genetic and gene regulatory variation, yet much less attention has been paid to the evolutionary processes that shape the observed differences in gene regulation between individuals in humans or any other primate. To begin addressing this gap, we performed a comparative analysis of gene expression variability and expression quantitative trait loci (eQTLs) in humans and chimpanzees, using gene expression data from primary heart samples. We found that expression variability in both species is often determined by non-genetic sources, such as cell-type heterogeneity. However, we also provide evidence that inter-individual variation in gene regulation can be genetically controlled, and that the degree of such variability is generally conserved in humans and chimpanzees. In particular, we found a significant overlap of orthologous genes associated with eQTLs in both species. We conclude that gene expression variability in humans and chimpanzees often evolves under similar evolutionary pressures.

Current or past history of >or= 4/8 CGD parameters is highly suggestive of chronic gout.

The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype.

While comparative functional genomic studies have shown that inter-species differences in gene expression can be explained by corresponding inter-species differences in genetic and epigenetic regulatory mechanisms, co-transcriptional mechanisms, such as alternative polyadenylation (APA), have received little attention. We characterized APA in lymphoblastoid cell lines from six humans and six chimpanzees by identifying and estimating usage for 44,432 polyadenylation sites (PAS) in 9,518 genes. Although APA is largely conserved, 1,705 genes showed significantly different PAS usage (FDR 0.05) between species. Genes with divergent APA also tend to be differentially expressed, are enriched among genes showing differences in protein translation, and can explain a subset of observed inter-species protein expression differences that do not differ at the transcript level. Finally, we found that genes with a dominant PAS, which is used more often than other PAS, are particularly enriched for differentially expressed genes.