Project description:Our histological findings showed that vermillion is present in the lip of Japanese macaque. In addition, the immunostaining pattern of K10 and SPRR3 of the lip of Japanese macaque is similar to that of a human. Thus, the transcriptome analysis of Japanese monkey can provide several unique genes specific to vermillion keratinocytes, which is required to develop a human lip/vermillion in vitro model.
Project description:Primary objectives: The primary objective is to investigate circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Primary endpoints: circulating tumor DNA (ctDNA) via deep sequencing for mutation detection and by whole genome sequencing for copy number analyses before start (baseline) with regorafenib and at defined time points during administration of regorafenib for treatment efficacy in colorectal cancer patients in terms of overall survival (OS).
Project description:Macaque species share over 93% genome homology with humans and develop many disease phenotypes similar to those of humans, making them valuable animal models for the study of human diseases (e.g.,HIV and neurodegenerative diseases). However, the quality of genome assembly and annotation for several macaque species lags behind the human genome effort. To close this gap and enhance functional genomics approaches, we employed a combination of de novo linked-read assembly and scaffolding using proximity ligation assay (HiC) to assemble the pig-tailed macaque (Macaca nemestrina) genome. This combinatorial method yielded large scaffolds at chromosome-level with a scaffold N50 of 127.5 Mb; the 23 largest scaffolds covered 90% of the entire genome. This assembly revealed large-scale rearrangements between pig-tailed macaque chromosomes 7, 12, and 13 and human chromosomes 2, 14, and 15. We subsequently annotated the genome using transcriptome and proteomics data from personalized induced pluripotent stem cells (iPSCs) derived from the same animal. Reconstruction of the evolutionary tree using whole genome annotation and orthologous comparisons among three macaque species, human and mouse genomes revealed extensive homology between human and pig-tailed macaques with regards to both pluripotent stem cell genes and innate immune gene pathways. Our results confirm that rhesus and cynomolgus macaques exhibit a closer evolutionary distance to each other than either species exhibits to humans or pig-tailed macaques. These findings demonstrate that pig-tailed macaques can serve as an excellent animal model for the study of many human diseases particularly with regards to pluripotency and innate immune pathways.
Project description:It has been thought that epigenetic changes underlie the evolutionary divergence of phenotype between closely related species. However, the manner in which epigenetic changes are generated remains unknown. Although whole-genome DNA methylation profiles in some somatic tissues and sperm have been reported for humans and chimpanzees, a systematic analysis of these data has been lacking. In this manuscript, therefore, we analyzed these methylomes in detail, identified genomic regions with different DNA methylation levels, and examined the cell-type specificity and its association with changes in genomic sequence. Moreover, we generated a methylation map of Japanese macaque sperm and used it as an out-group to infer the evolutional history of methylation in these regions.
Project description:We examined the histone modification H3K4 dimethylation (H3K4me2) in the prefrontal cortex of individual Rhesus macaques at different ages by chromatin immunoprecipitation, followed by deep sequencing (ChIP-seq) at the whole genome level Four Rhesus macaque prefrontal cortex samples with 0.4, 9,22 and 26 years old were used for H3K4me2 ChIP-Seq