Journal of Genetics and Genomics

Creating future crops: a revolution for sustainable agriculture

Tao Guo, Hong-Xuan Lin

2021, 48(2): 97-101. doi: 10.1016/j.jgg.2021.02.002

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The challenge of emerging SARS-CoV-2 mutants to vaccine development

Rong Li, Jun Liu, Hui Zhang

2021, 48(2): 102-106. doi: 10.1016/j.jgg.2021.03.001

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COVID-19 mRNA vaccines

Qingrui Huang, Jiawei Zeng, Jinghua Yan

2021, 48(2): 107-114. doi: 10.1016/j.jgg.2021.02.006

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The ongoing COVID-19 pandemic and its unprecedented global societal and economic disruptive impact highlight the urgent need for safe and effective vaccines. Taking substantial advantages of versatility and rapid development, two mRNA vaccines against COVID-19 have completed late-stage clinical assessment at an unprecedented speed and reported positive results. In this review, we outline keynotes in mRNA vaccine development, discuss recently published data on COVID-19 mRNA vaccine candidates, focusing on those in clinical trials and analyze future potential challenges.

CRISPR-mediated host genomic DNA damage is efficiently repaired through microhomology-mediated end joining in Zymomonas mobilis

Xiaojie Wang, Bo Wu, Xin Sui, Zhufeng Zhang, Tao Liu, Yingjun Li, Guoquan Hu, Mingxiong He, Nan Peng

2021, 48(2): 115-122. doi: 10.1016/j.jgg.2021.02.012

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CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against mobile genetic elements (MGEs) through uptake of invader-derived spacers. De novo adaptation samples spacers from both invaders and hosts, whereas primed adaptation shows higher specificity to sample spacers from invaders in many model systems as well as in the subtype I-F system of Zymomonas mobilis. Self-derived spacers will lead to CRISPR self-interference. However, our in vivo study demonstrated that this species used the microhomology-mediated end joining (MMEJ) pathway to efficiently repair subtype I-F CRISPR-Cas system-mediated DNA breaks guided by the self-targeting spacers. MMEJ repair of DNA breaks requires direct microhomologous sequences flanking the protospacers and leads to DNA deletions covering the protospacers. Importantly, CRISPR-mediated genomic DNA breaks failed to be repaired via MMEJ pathway in presence of higher copies of short homologous DNA. Moreover, CRISPR-cleaved exogenous plasmid DNA was failed to be repaired through MMEJ pathway, probably due to the inhibition of MMEJ by the presence of higher copies of the plasmid DNA inZ. mobilis. Our results infer that MMEJ pathway discriminates DNA damages between in the host chromosome versus mobile genetic element (MGE) DNA, and maintains genome stability post CRISPR immunity in Z. mobilis.

The chromatin remodeling complex imitation of switch controls stamen filament elongation by promoting jasmonic acid biosynthesis in Arabidopsis

Youshang Zhao, Ting Jiang, Lei Li, Xiaotuo Zhang, Tianyu Yang, Cuimei Liu, Jinfang Chu, Binglian Zheng

2021, 48(2): 123-133. doi: 10.1016/j.jgg.2021.02.003

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Plant reproduction requires the coordinated development of both male and female reproductive organs. Jasmonic acid (JA) plays an essential role in stamen filament elongation. However, the mechanism by which the JA biosynthesis genes are regulated to promote stamen elongation remains unclear. Here, we show that the chromatin remodeling complex Imitation of Switch (ISWI) promotes stamen filament elongation by regulating JA biosynthesis. We show that AT-Rich Interacting Domain 5 (ARID5) interacts with CHR11, CHR17, and RLT1, several known subunits of ISWI. Mutations in ARID5 and RLTs caused a reduced seed set due to greatly shortened stamen filaments. RNA-seq analyses reveal that the expression of key genes responsible for JA biosynthesis is significantly down-regulated in the arid5 and rlt mutants. Consistently, the JA levels are drastically decreased in both arid5 and rlt mutants. Chromatin immunoprecipitation-quantitative PCR analyses further show that ARID5 is recruited to the chromatin of JA biosynthesis genes. Importantly, exogenous JA treatments can fully rescue the defects of stamen filament elongation in both arid5 and rlt mutants, leading to the partial recovery of fertility. Our results provide a clue how JA biosynthesisis positively regulated by the chromatin remodeling complex ISWI, thereby promoting stamen filament elongation in Arabidopsis.

Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Lin Zhu, Xiaoyan Yang, Juyi Li, Xiong Jia, Xiangli Bai, Ying Zhao, Wenzhuo Cheng, Meng Shu, Yan Zhu, Si Jin

2021, 48(2): 134-146. doi: 10.1016/j.jgg.2021.01.008

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Gene therapy has become the most effective treatment for monogenic diseases. Congenital LEPTIN deficiency is a rare autosomal recessive monogenic obesity syndrome caused by mutations in the Leptin gene. Ob/ob mouse is a monogenic obesity model, which carries a homozygous point mutation of C to T in Exon 2 of the Leptin gene. Here, we attempted to edit the mutated Leptin gene in ob/ob mice preadipocytes and inguinal adipose tissues using CRISPR/Cas9 to correct the C to T mutation and restore the production of LEPTIN protein by adipocytes. The edited preadipocytes exhibit a correction of 5.5% ofLeptin alleles and produce normal LEPTIN protein when differentiated into mature adipocytes. The ob/ob mice display correction of 1.67% of Leptin alleles, which is sufficient to restore the production and physiological functions of LEPTIN protein, such as suppressing appetite and alleviating insulin resistance. Our study suggests CRISPR/Cas9-mediated in situ genome editing as a feasible therapeutic strategy for human monogenic diseases, and paves the way for further research on efficient delivery system in potential future clinical application.

A single-cell atlas of mouse olfactory bulb chromatin accessibility

Yin Chen, Xiangning Ding, Shiyou Wang, Peiwen Ding, Zaoxu Xu, Jiankang Li, Mingyue Wang, Rong Xiang, Xiaoling Wang, Haoyu Wang, Qikai Feng, Jiaying Qiu, Feiyue Wang, Zhen Huang, Xingliang Zhang, Gen Tang, Shengping Tang

2021, 48(2): 147-162. doi: 10.1016/j.jgg.2021.02.007

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Olfaction, the sense of smell, is a fundamental trait crucial to many species. The olfactory bulb (OB) plays pivotal roles in processing and transmitting odor information from the environment to the brain. The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing. However, the epigenetic landscape of the mOB remains mostly unexplored. Herein, we apply single-cell assay for transposase-accessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the mOB. Based on single-cell epigenetic signatures, mOB cells are classified into 21 clusters corresponding to 11 cell types. We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred. In addition, the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage. Our study provides a valuable epigenetic data set for the mOB at single-cell resolution, and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.

Rapid and efficient wounding for in vivo studies of neuronal dendrite regeneration and degeneration

Jianzhi Zhao, Xiaojie Wang, Xinan Meng, Wei Zou, Suhong Xu

2021, 48(2): 163-166. doi: 10.1016/j.jgg.2020.10.003

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A custom-designed panel sequencing study in 201 Chinese patients with craniosynostosis revealed novel variants and distinct mutation spectra

Yingzhi Wu, Meifang Peng, Jieyi Chen, Jinlong Suo, Sihai Zou, Yanqing Xu, Andrew O.M. Wilkie, Weiguo Zou, Xiongzheng Mu, Sijia Wang

2021, 48(2): 167-171. doi: 10.1016/j.jgg.2020.11.004

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2021 Vol. 48, No. 2