Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants

He, Yaoxi; Luo, Xin; Zhou, Bin; Hu, Ting; Meng, Xiaoyu; Audano, Peter A.; Kronenberg, Zev; Eichler, Evan E.; Jin, Jie; Guo, Yongbo; Yang, Yanan; Qi, Xuebin; Su, Bing

doi:10.1038/s41467-019-12174-w

Cited by 66 publications

(68 citation statements)

References 78 publications

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“…SV filtering was performed with the following criteria: (1) SV quality was evaluated with “PASS”; (2) SVs with precise breakpoints; (3) SVs with >10 supported reads; (4) SV length between 50 bp and 2 Mb (>2 Mb-length SVs were manually checked and we did not see any); (5) overlap the SV sets from Delly and Pindel (an overlapped SV was defined when the overlapped length is more than 50% of the reciprocal similarity). De novo SV filtering included the following criteria: (1) the shared SVs between parents and offspring were excluded (parent-inherit); (2) the SVs included in the public SV database or reported as common SVs in populations 41 (known SV filtering); (3) the SVs shared among the offspring were removed (cross-filtering). (4) IGV tool was used to manually check the candidate SVs and filtered out SVs according to the alignment and coverage situations.…”

Section: Methodsmentioning

confidence: 99%

Trio deep-sequencing does not reveal unexpected off-target and on-target mutations in Cas9-edited rhesus monkeys

Luo

Zhang³

et al. 2019

Nat Commun

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CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect and on-target complex mutations remain a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, to our knowledge no comprehensive in vivo off-target and on-target assessment has been conducted in NHPs. Here, we perform whole genome trio sequencing of Cas9-treated rhesus monkeys. We only find a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected off-target mutations (OTMs) were detected. Furthermore, the long-read sequencing data does not detect large structural variants in the target region.

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Section: Methodsmentioning

confidence: 99%

Trio deep-sequencing does not reveal unexpected off-target and on-target mutations in Cas9-edited rhesus monkeys

Luo

Zhang³

et al. 2019

Nat Commun

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“…A rhesus macaque model of health and ageing Rhesus macaques ( Macaca mulatta ) are the most common NHP in captivity and have been a useful model for human ageing for decades [22][23][24][25]. As a major biomedical model, rhesus macaques are the beneficiaries of investment in major resources including high-quality genome assemblies [24,26] and neuroanatomical atlases [27]. The rhesus macaque lifespan is approximately 3-4 times shorter than that of humans ( figure 1), yet within this compressed period ageing macaques exhibit a host of parallel declines in physical health, physiological integrity, and brain function [23].…”

Section: Models For Human Health and Ageingmentioning

confidence: 99%

Rhesus macaques as a tractable physiological model of human ageing

Chiou

Montague

Goldman

et al. 2020

Preprint

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Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from shorter-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research due to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population.

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“…2013 ). Recently, the single-molecule assembly of Chinese rhesus macaque ( He et al. 2019 ) has been reported.…”

Section: Discussionmentioning

confidence: 99%

Genomic Copy Number Variation Study of Nine Macaca Species Provides New Insights into Their Genetic Divergence, Adaptation, and Biomedical Application

Fan

Shen

et al. 2020

Genome Biology and Evolution

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Copy number variation (CNV) can promote phenotypic diversification and adaptive evolution. However, the genomic architecture of CNVs among Macaca species remains scarcely reported, and the roles of CNVs in adaptation and evolution of macaques have not been well addressed. Here, we identified and characterized 1479 genome-wide hetero-specific CNVs across nine Macaca species with bioinformatic methods, along with 26 CNV-dense regions and dozens of lineage-specific CNVs. The genes intersecting CNVs were overrepresented in nutritional metabolism, xenobiotics/drug metabolism, and immune related pathways. Population-level transcriptome data showed that nearly 46% of CNV genes were differentially expressed across populations and also mainly consisted of metabolic and immune related genes, which implied the role of CNVs in environmental adaptation of Macaca. Several CNVs overlapping drug metabolism genes were verified with genomic qPCR, suggesting that these macaques may have different drug metabolism features. The CNV-dense regions, including fifteen first reported here, represent unstable genomic segments in macaques where biological innovation may evolve. Twelve gains and forty losses specific to the Barbary macaque contain genes with essential roles in energy homeostasis and immunity defence, inferring the genetic basis of its unique distribution in North Africa. Our study not only elucidated the genetic diversity across Macaca species from the perspective of structural variation, but also provided suggestive evidence for the role of CNVs in adaptation and genome evolution. Additionally, our findings provide new insights into the application of diverse macaques to drug study.

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Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants

Cited by 66 publications

References 78 publications

Trio deep-sequencing does not reveal unexpected off-target and on-target mutations in Cas9-edited rhesus monkeys

Trio deep-sequencing does not reveal unexpected off-target and on-target mutations in Cas9-edited rhesus monkeys

Rhesus macaques as a tractable physiological model of human ageing

Genomic Copy Number Variation Study of Nine Macaca Species Provides New Insights into Their Genetic Divergence, Adaptation, and Biomedical Application

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