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Sequence Diversity Analyses of an Improved Rhesus Macaque Genome Enhance its Biomedical Utility

Warren  et al., Science. 2020.

https://science.sciencemag.org/content/370/6523/eabc6617

Investigators sequenced and assembled an Indian-origin female rhesus macaque (RM) genome using a multiplatform genomics approach that included long-read sequencing, extensive manual curation, and experimental validation to generate a new comprehensive annotated reference genome. As a result, 99.7% of the gaps in the earlier draft genome are now closed, and more than 99% of the genes are represented. Whole-genome sequencing of 853 RMs of both sexes identified 85.7 million single-nucleotide variants and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay. The improved assembly of segmental duplications, new lineage-specific genes and expanded gene families provide a framework for developing noninvasive NHP models for human disease, as well as studies of genetic variation and phenotypic consequences. Supported by ORIP (P51OD011106, P51OD011107, P51OD011132, P51OD011104, U42OD024282, U42OD010568, R24OD011173, R24OD021324, R24OD010962), NHGRI, NIMH, NHLBI, and NIGMS.

The Immune Landscape in Tuberculosis Reveals Populations Linked to Disease and Latency

Esaulova  et al., Cell Host Microbe. 2020.

https://pubmed.ncbi.nlm.nih.gov/33340449/

Mycobacterium tuberculosis infection of adult rhesus macaques (RMs), predominantly males (81%), recapitulates both latent (LTBI) and active pulmonary TB (PTB) observed in humans. The immune characterization in lungs of RMs with PTB exhibited an influx of plasmacytoid dendritic cells, an interferon-responsive macrophage population, and activated T cell responses. In contrast, a CD27+ natural killer (NK) cell subset accumulated in the lungs of RMs with LTBI. This NK cell population was also detected in the circulation of humans with LTBI. This characterization of lung immune cells enhances our understanding of TB immunopathogenesis and provides potential targets for therapies and vaccines for TB control. Supported by ORIP (P51OD011104 and P51OD011133), NHLBI, and NIAID.