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Categorization of genes with strong correlation between DNA methylation and expression levels. (A) Classification of 89 genes with brain region–specific characteristics and differentially methylated genes (DMGs). Sites with significant changes (Fisher’s exact test; q-value ≤ 0.05) in CpG islands (CGIs) within the 2-kb sequence upstream of the gene were defined as DMGs, and the brain regions were pointed in a dot below. The p-values and r-values of the genes in the corresponding categories were determined by boxplot using Pearson’s correlation test. (B), (C) Gene set enrichment network using Ingenuity Pathway Analysis (IPA) of positively and negatively correlated genes. We revealed the correlation from 92 genes and finally selected 21 genes (Pearson’s correlation test; p-value ≤ 0.01). The DNA methylation level (D) and gene expression values (E) were shown in heatmaps. The columns ordered in the heatmaps from left to right were ventrolateral prefrontal cortex, hippocampus middle, cingulate gyrus angular gyrus, anterior caudate, dorsolateral prefrontal cortex, and inferior temporal lobe.
Source publication
The crab-eating monkey is widely used in biomedical research for pharmacological experiments. Epigenetic regulation in the brain regions of primates involves complex patterns of DNA methylation. Previous studies of methylated CpG-binding domains using microarray technology or peak identification of sequence reads mostly focused on developmental sta...
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Background:
The HIV-1 proviral genome harbors multiple CpG islands (CpGIs), both in the promoter and intragenic regions. DNA methylation in the promoter region has been shown to be heavily involved in HIV-1 latency regulation in cultured cells. However, its exact role in proviral transcriptional regulation in infected individuals is poorly underst...
Citations
... But, the covariant needs to be figured out with detail sample information. The crab-eating macaque, also refers to long-tailed monkey, is the most studied non-human primate and exhibits marked similarities to humans in almost all aspects of their anatomy, endocrinology, and physiology [29,30]. In our study, we also found the identical viral binding sites of ACE2 in crab-eating macaque with those of human compared to other animal models, suggesting it an ideal animal model for research of COVID-19. ...
Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), a novel coronavirus, which results in corona virus disease 2019 (COVID-19), has caused over 40 millions of people infected and over 1 million fatalities, challenging the public health. The recognition of its functional receptor, angiotensin converting enzyme 2 (ACE2), have facilitated the antivirus drugs testing and vaccines development. Due to the natural resistance of mouse model to SARS-Cov-2, there is an urgent need to find out the alternative animal model. Considering the crucial role of ACE2 in the host cell entry, we analyzed the phylogeny and expression pattern of ACE2 from various mammals. Firstly, crab-eating macaque possesses all of the 5 identical hotspot residues with human, suggesting high likelihood of interaction between ACE2 and spike protein of SARS-CoV-2 to occur. Cattle and pig show 4 identical sites. Ferret, cat and dog possess 3 identical sites. Bat and mouse only share 2 same amino acids with human. Secondly, in humans, ACE2 is widely present, with particularly high expression in adipose, thyroid, lung and colon tissues. In crab-eating macaque, liver, lung, thyroid and colon showed high expression level of ACE2. For dog, ACE2 is most highly expressed in colon with obvious differential expression level between female and male group. The results would provide clues for establishing the appropriate animal model in the research and clinical cure of COVID-19.
... Average beta values were used for comparison with the published dataset. 13 ...
... Because the DNA methylation study using the occipital lobe of the crab-eating macaque has not been released, we utilized a previous study that reported methylated regions of seven different brain regions of the crab-eating macaque. 13 Within the 1310 methylated regions reported, 13 a total of 2844 high-confidence CpG probes were included. Comparison of DNA methylation levels revealed high consistency with different brain regions (R = 0.709 for the hippocampus to 0.743 for the inferior temporal lobe, average R for the seven brain regions was 0.733) (Figure 2). ...
... Because the DNA methylation study using the occipital lobe of the crab-eating macaque has not been released, we utilized a previous study that reported methylated regions of seven different brain regions of the crab-eating macaque. 13 Within the 1310 methylated regions reported, 13 a total of 2844 high-confidence CpG probes were included. Comparison of DNA methylation levels revealed high consistency with different brain regions (R = 0.709 for the hippocampus to 0.743 for the inferior temporal lobe, average R for the seven brain regions was 0.733) (Figure 2). ...
Background:
Commercially available Illumina DNA methylation arrays (HumanMethylation 27K, HumanMethylation450, and MethylationEPIC BeadChip) can be used for comprehensive DNA methylation analyses of not only the human genome but also other mammalian genomes, ranging from those of nonhuman primates to those of rodents. However, practical application of the EPIC array to the crab-eating macaque has not been reported.
Methods:
Through bioinformatic analyses involving cross-species comparison and consideration of probe performance, we selected array probes that can be reliably used for the crab-eating macaque genome. A DNA methylation assay using an EPIC array was performed on genomic DNA extracted from the brains of five crab-eating macaques. The obtained DNA methylation data were compared with a publicly available dataset.
Results:
Among the 865 918 probes in the EPIC array, a total of 183 509 probes (21.2%) were selected as high-confidence array probes in the crab-eating macaque. Subsequent comparisons revealed that the data from these probes showed good concordance with other DNA methylation datasets of the crab-eating macaque.
Conclusion:
The selected high-confidence array probes would be useful for high-throughput DNA methylation assays of the crab-eating macaque.
Functional genomics research is continually improving our understanding of genotype-phenotype relationships in humans, and comparative genomics perspectives can provide additional insight into the evolutionary histories of such relationships. To specifically identify conservation or species-specific divergence in humans, we must look to our closest extant evolutionary relatives. Primate functional genomics research has been steadily advancing and expanding, in spite of several limitations and challenges that this field faces. New technologies and cheaper sequencing provide a unique opportunity to enhance and expand primate comparative studies, and we outline possible paths going forward. The potential human-specific insights that can be gained from primate functional genomics research are substantial, and we propose that now is a prime time to expand such endeavors.
Proliferative vasculopathy and hydranencephaly‐hydrocephaly syndrome (PVHH, OMIM 225790), also known as Fowler syndrome, is a rare autosomal recessive disorder of brain angiogenesis. PVHH has long been considered to be prenatally lethal. We evaluated the phenotypes of the first three siblings with survival into adulthood, performed a systematic review of the Fowler syndrome literature and delineated genotype‐phenotype correlations using a scoring system to rate the severity of the disease. Thirty articles were included, describing 69 individual patients. To date, including our clinical reports, 72 patients have been described with Fowler syndrome. Only 6/72 (8%) survived beyond birth. Although our three patients carry the same mutations (c.327T>A‐p.Asn109Lys and c.887C>T‐p.Ser296Leu) in FLVCR2, only two of them presented with the same cerebral features, ventriculomegaly and cerebral calcifications, as affected fetuses. The third sibling has a surprisingly milder clinical and radiological phenotype, suggesting intrafamilial variability. Although no clear phenotype‐genotype correlation exists, some variants appear to be associated with a less severe phenotype compatible with life. As such, it is important to consider Fowler syndrome in patients with gross ventriculomegaly, cortical malformations and/or cerebral calcifications on brain imaging.
