Identification of DNA methylation differences correlated with transcriptional divergence between humans and chimpanzees in chromosomes 21 and 22
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens Pan troglodytes
PROVIDER: GSE35475 | GEO | 2012/02/02
SECONDARY ACCESSION(S): PRJNA152359
REPOSITORIES: GEO
Similar Datasets
Project description:Genome wide DNA methylation profiling of captive chimpanzees of ages spanning the chimpanzee lifespan (whole blood) Methylation levels have been shown to change with age at sites across the human genome. Change at some of these sites is so consistent across individuals that it can be used as an “epigenetic clock” to predict an individual’s chronological age within a few years. Studies of age-related epigenetic change in other mammals, including mice, whales, and canids, show that some but not all of the same loci as in humans undergo age-associated methylation changes. An in-depth comparison of chimpanzees with humans is of interest because the two species are genetically similar but differ in lifespan. To this end, we profiled genome-wide blood methylation levels for 113 samples from 83 chimpanzees aged 1-58 years (26 chimpanzees were sampled at multiple ages during their lifespan). We used this data to build a chimpanzee-specific epigenetic clock model as well as to compare genome-wide patterns of change with age between humans and chimpanzees more generally.
2020-08-23 | GSE136296 | GEO
Project description:Identification of DNA methylation differences correlated with transcriptional divergence between humans and chimpanzees in chromosomes 21 and 22
| PRJNA152359 | ENA
Project description:Despite the close evolutionary relationship and striking genetic similarity between humans and chimpanzees, there are remarkable differences in anatomy, behavior, and disease susceptibility in the two species. One step towards understanding the biological basis of these phenotypic differences is to characterize quantitative differences in levels of expression of genes in humans and chimpanzees. To contribute to such analysis, we compared gene expression patterns in lymphoblastoid cell lines between nine unrelated humans and ten unrelated chimpanzees by using human cDNA microarrays. Hybridizations to arrays containing 43,233 features produced high quality data for 22,879 cDNA clones, representing 20,266 Unigenes. We observed statistically significant differences in transcript levels for 32% of these genes (P < 0.05, Student t test), with about 200 cDNAs showing differences of more than 2-fold (lower bounds of 95% confidence interval). Among these are genes involved in cell surface glycosylation and responses to toxins and viruses. Examination of functional annotations for the differentially expressed genes revealed lower expression of cell cycle and energy pathways genes, and higher expression of chemokines, 26S proteasome and cell motility genes in chimpanzee samples. These genes and pathways could underlie some of the phenotypic differences between humans and chimpanzees. Keywords: other
2005-06-08 | GSE1464 | GEO
Project description:Sixty-one array-CGH experiments were performed on the human WGTP platform, comparing: (1) 30 unrelated chimpanzees to a single chimpanzee reference individual, (2) 30 unrelated humans to a single human reference individual and (3) the chimpanzee reference individual to the human reference individual.
2008-08-28 | E-TABM-479 | biostudies-arrayexpress
Project description:Complete genome sequencing has identified millions of DNA changes that differ between humans and chimpanzees. Although a subset of these changes likely underlies important phenotypic differences between humans and chimpanzees, it is currently difficult to distinguish causal from incidental changes and to map specific phenotypes to particular genome locations. To facilitate further genetic study of human-chimpanzee divergence, we have generated human and chimpanzee auto-tetraploids and allo-tetraploids by fusing induced pluripotent stem cells (iPSCs) of each species. The resulting tetraploid iPSCs can be stably maintained and retain the ability to differentiate along ectoderm, mesoderm, and endoderm lineages. RNA sequencing identifies thousands of genes whose expression differs between humans and chimpanzees when assessed in single-species diploid or auto-tetraploid iPSCs. Analysis of gene expression patterns in inter-specific allo-tetraploid iPSCs shows that human-chimpanzee expression differences arise from substantial contributions of both cis-acting changes linked to the genes themselves, and trans-acting changes elsewhere in the genome. To enable further genetic mapping of species differences, we tested chemical treatments for stimulating genome-wide mitotic recombination between human and chimpanzee chromosomes, and CRISPR methods for inducing species-specific changes on particular chromosomes in allo-tetraploid cells. We successfully generated derivative cells with nested deletions or inter-specific recombination on the X chromosome. These studies identify a long distance cis-regulatory domain of the Fragile X-associated gene (FMR1), confirm an important role for the X chromosome in trans-regulation of other expression differences, and illustrate the potential of this system for more detailed mapping of the molecular basis of human and chimpanzee evolution.
2021-11-29 | GSE184768 | GEO
Project description:The chimpanzee is the only model other than man for investigating the pathogenesis of viral hepatitis types A through E. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host response to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), was compared in multiple experimentally-infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. The comparison utilized a permutational t-test-based analysis of selected time points. More specifically, baseline samples were compared with post-inoculation samples that were strategically chosen based on their relationship to viremia, and probe sequences were aligned to the human and chimpanzee genome sequences to assess their relative sensitivity for detecting differentially expressed genes. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust than the response to HEV infection.
2010-09-22 | GSE22160 | GEO
Project description:Differences in gene regulation contribute to phenotypic differences between humans and other primates. While co-transcriptional gene regulatory mechanisms such as alternative polyadenylation (APA) can help explain how variation in gene regulation manifests, such mechanisms remain understudied. We measured polyadenylation site (PAS) usage in a panel of 6 human and 6 chimpanzee lymphoblastoid cell lines (LCLs). While APA is largely conserved between humans and chimpanzees, genes with divergent APA patterns are enriched among differentially expressed and differentially translated genes. Differential usage of 3’ UTR and intronic PAS are both significantly correlated with differential mRNA expression effect sizes but in opposite directions. For many genes, there is one PAS dominant, meaning it is used much more often than others. The dominant PAS for these gene is overwhelmingly shared between species, however, differences in dominant PAS are enriched for genes with expression differences. Finally, through post-translational mechanisms, we believe APA contributes to genes differentially expressed at the protein level but not in mRNA. As this is the first primate comparative study of APA, our study establishes APA as a key mechanism underlying the genetic regulation of gene and protein expression levels in primates.
2021-01-22 | GSE155245 | GEO
Project description:The chimpanzee is the only model other than man for investigating the pathogenesis of viral hepatitis types A through E. Studies of the host response, including microarray analyses, have relied on the close relationship between these two primate species: chimpanzee samples are commonly tested with human-based reagents. In this study, the host response to two dissimilar viruses, hepatitis E virus (HEV) and hepatitis C virus (HCV), was compared in multiple experimentally-infected chimpanzees. Affymetrix U133+2.0 human microarray chips were used to assess the entire transcriptome in serial liver biopsies obtained over the course of the infections. The comparison utilized a permutational t-test-based analysis of selected time points. More specifically, baseline samples were compared with post-inoculation samples that were strategically chosen based on their relationship to viremia, and probe sequences were aligned to the human and chimpanzee genome sequences to assess their relative sensitivity for detecting differentially expressed genes. Regardless of the viral infection, the alignment of differentially expressed genes to the human genome sequence resulted in a larger number of genes being identified when compared with alignment to the chimpanzee genome sequence. This probably reflects the lesser refinement of gene annotation for chimpanzees. In general, the two viruses demonstrated very distinct temporal changes in host response genes, although both RNA viruses induced genes that were involved in many of the same biological systems, including interferon-induced genes. The host response to HCV infection was more robust than the response to HEV infection. Three chimpanzees were inoculated intravenously with the hepatitis C virus: chimp 1628 was infected with < 100 infectious doses (ID) of the H77 strain (genotype 1a) (30); chimp 1417 was infected with an unknown titer, in serum, of the HC-J6 strain (genotype 2a) (31); chimp 1422 was infected with an unknown titer, in serum, of the T.N. strain (genotype 1a) (35). Four chimpanzees (CH1616, CH1618, CH1374 and CH1375) were inoculated intravenously with 0.5 ml of the HEV SAR55 strain (genotype 1) at approximately 10^6 ID. Grouping of the biological replicates was based on viremia: groups consisted of the first positive week (and the second positive week for HCV), the peak positive week, the last positive week, the first negative week and the fourth negative week. There were 3 biological replicates for HCV. The 4 replicates for HEV were both biological and technical. For chimp 1417, 7 samples were taken between weeks 0 and 17. For chimp 1422, 8 samples were taken between weeks 0 and 13. For chimp 1628, 8 samples were taken between weeks 0 and 19. For chimp 1374, 6 samples were taken between weeks 0 and 8. For chimp 1375, 4 samples were taken between weeks 0 and 8. For chimp 1616, 5 samples were taken between weeks 0 and 7. For chimp 1618, 6 samples were taken between weeks 0 and 8. Normalized probe set level data not provided for individual Sample records. Processed data is available on Series record.
2010-09-21 | E-GEOD-22160 | biostudies-arrayexpress
Project description:Genome-wide prefrontal cortex and cerebellum DNA methylation profiles of younger and older adult humans, captive chimpanzees, and captive rhesus macaques
2021-04-07 | GSE154403 | GEO
Project description:Hepatitis A virus (HAV) is a hepatotropic human picornavirus that has been associated only with acute infection. Its pathogenesis is not well understood since there have been few recent studies in animal models using modern methodologies. We characterized HAV infections in three chimpanzees, quantifying viral RNA by qRT-PCR and examining critical aspects of the innate immune response including intrahepatic interferon-stimulated gene expression. We compared these infection profiles with similar studies of chimpanzees infected with hepatitis C virus (HCV), a hepatotropic flavivirus that frequently causes persistent infection. Surprisingly, HAV-infected animals exhibited very limited induction of type I interferon-stimulated genes in the liver compared to chimpanzees with acute resolving HCV infection, despite similar levels of viremia and 100-fold greater quantities of viral RNA in the liver. Minimal ISG15 and IFIT1 responses peaked 1-2 weeks after HAV challenge, then subsided despite continuing high hepatic viral loads. An acute inflammatory response at 3-4 weeks correlated with the appearance of virus-specific antibodies, and both apoptosis and proliferation of hepatocytes. Despite this, HAV RNA persisted in the liver for months, remaining present long after its clearance from serum and feces and revealing dramatic differences in the kinetics of clearance in the three compartments. Viral RNA was detected in the liver for significantly longer (35 to >48 weeks) than HCV RNA in animals with acute resolving HCV infection (10-20 weeks). Collectively, these findings suggest that early HAV infection is far stealthier than HCV infection and represents a distinctly different paradigm in viral-host interactions within the liver. Chimpanzee liver was biopsied during an acute HAV infection. Chimp 1 and 2 had two baseline samples. Chimp 3 used the baselines from chimps 1 and 2. Chimp 1 had 8 samples during the HAV acute infection. Chimp 2 had 9 samples during the HAV acute infection. Chimp 3 had 4 samples during the HAV acute infection.
2011-03-09 | E-GEOD-27850 | biostudies-arrayexpress