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.
2020-05-04 | PXD018943 | Pride
Project description:Macaca nemestrina (pig-tailed macaque) genome, mMacNem1, sequence data
Project description:Progestin-based contraception may increase the risk of vaginal HIV acquisition to a level greater than the progesterone-rich luteal phase of the menstrual cycle, which has been demonstrated to have a significantly higher transmission rate compared to the follicular phase. We used pig-tailed macaque (Macaca nemestrina) model to evaluate the effects of administration of the oral the combined oral contraceptives (COCs) depot medroxyprogesterone acetate (DMPA) and levonorgestrel (LNG) on mucosal factors that influence HIV susceptibility. We compared the pH and vaginal epithelial thickness data from previous studies, and evaluated contraception-induced molecular changes in the vagina using transcriptional and cytokine profiling. The administration of DMPA caused a pronounced thinning of the vaginal epilthelium relative to measurements takein in the follicular or luteal phase. DMPA also induced a significant increase in vaginal IL10 expression. Lastly, using RNA-Seq analyses of vaginal biopsies, we noted that both DMPA- and LNG-based contraception induced a signature of gene expression similar to that of the luteal phase, only more exacerbated, and including widespread down-regulation of HIV-restriction genes. Use of progestin-based contraception might engender a milieu that poses an increased risk of HIV transmission than that of the luteal phase via vaginal thinning, induction of immunosuppressive cytokines, and widespread suppression of HIV restriction factors.
Project description:Macaca fascicularis (long-tailed, cynomolgus, or crab-eating macaque) is a highly advantageous model in which to study human cochlea with regard to both evolutionary proximity and physiological similarity of the auditory system. To better understand the properties of primate cochlear function, we analyzed the genes predominantly expressed in M. fascicularis cochlea.