Journal of Genetics and Genomics

Plant pan-genomics: recent advances, new challenges, and roads ahead

Wei Li, Jianan Liu, Hongyu Zhang, Ze Liu, Yu Wang, Longsheng Xing, Qiang He, Huilong Du

2022, 49(9): 833-846. doi: 10.1016/j.jgg.2022.06.004

Abstract (451) PDF (64)

Abstract:
Pan-genomics can encompass most of the genetic diversity of a species or population and has proved to be a powerful tool for studying genomic evolution and the origin and domestication of species, and for providing information for plant improvement. Plant genomics has greatly progressed because of improvements in sequencing technologies and the rapid reduction of sequencing costs. Nevertheless, pan-genomics still presents many challenges, including computationally intensive assembly methods, high costs with large numbers of samples, ineffective integration of big data, and difficulty in applying it to downstream multi-omics analysis and breeding research. In this review, we summarize the definition and recent achievements of plant pan-genomics, computational technologies used for pan-genome construction, and the applications of pan-genomes in plant genomics and molecular breeding. We also discuss challenges and perspectives for future pan-genomics studies and provide a detailed pipeline for sample selection, genome assembly and annotation, structural variation identification, and construction and application of graph-based pan-genomes. The aim is to provide important guidance for plant pan-genome research and a better understanding of the genetic basis of genome evolution, crop domestication, and phenotypic diversity for future studies.

Loss of Wtap results in cerebellar ataxia and degeneration of Purkinje cells

Yeming Yang, Guo Huang, Xiaoyan Jiang, Xiao Li, Kuanxiang Sun, Yi Shi, Zhenglin Yang, Xianjun Zhu

2022, 49(9): 847-858. doi: 10.1016/j.jgg.2022.03.001

Abstract (217) PDF (25)

Abstract:
N⁶-methyladenosine (m⁶A) modification, which is achieved by the METTL3/METTL14/WTAP methyltransferase complex, is the most abundant internal mRNA modification. Although recent evidence indicates that m⁶A can regulate neurodevelopment as well as synaptic function, the roles of m⁶A modification in the cerebellum and related synaptic connections are not well established. Here, we report that Purkinje cell (PC)-specific WTAP knockout mice display early-onset ataxia concomitant with cerebellar atrophy due to extensive PC degeneration and apoptotic cell death. Loss of Wtap also causes the aberrant degradation of multiple PC synapses. WTAP depletion leads to decreased expression levels of METTL3/14 and reduced m⁶A methylation in PCs. Moreover, the expression of GFAP and NF-L in the degenerating cerebellum is increased, suggesting severe neuronal injuries. In conclusion, this study demonstrates the critical role of WTAP-mediated m⁶A modification in cerebellar PCs, thus providing unique insights related to neurodegenerative disorders.

Deletion of CHD8 in cerebellar granule neuron progenitors leads to severe cerebellar hypoplasia, ataxia, and psychiatric behavior in mice

Xiang Chen, Tong Chen, Chen Dong, Huiyao Chen, Xinran Dong, Lin Yang, Liyuan Hu, Huijun Wang, Bingbing Wu, Ye Yao, Yu Xiong, Man Xiong, Yifeng Lin, Wenhao Zhou

2022, 49(9): 859-869. doi: 10.1016/j.jgg.2022.02.011

Abstract (260) PDF (10)

Abstract:
CHD8 is a candidate gene for autism spectrum disorders and neurological development delay. It has been reported to be essential for neurogenesis in the cerebral cortex, but the function of CHD8 in cerebellum has not been comprehensively investigated. The potential relationship of cerebellum dysplasia with psychiatric disorders in patients with CHD8 mutations is still not clear. In this study, we establish different conditional knockout mouse models to investigate the roles of CHD8 in cerebellar development. Mice with neural stem cell-specific Chd8 deletion exhibit significant reduction of cerebellum volume and no layering structure is detected. Genetic deletion of Chd8 in cerebellar granule neuron progenitors (GNPs) leads to cerebellar hypoplasia, absent of proliferation layer and ectopic of Purkinje neuron. However, no substantial cerebellar dysplasia is detected in mice with Purkinje neuron- or oligodendrocyte-specific Chd8 ablation. Single-cell RNA sequencing indicates that ribosome-related genes and pathways are most significantly disrupted in GNPs, indicating the potential mechanism. Importantly, in addition to the ataxia phenotype, mice with GNP-specific Chd8 ablation present a neuropsychiatric phenotype in three-chamber and light/dark tests. Taken together, our results provide insights not only into the function of CHD8 in cerebellar development, but also the pathogenesis of neuropsychiatric disorders in patients with CHD8 mutations.

OsASHL1 and OsASHL2, two members of the COMPASS-like complex, control floral transition and plant development in rice

Guangxin Zhao, Jingying Wang, Xi Chen, Hanjing Sha, Xin Liu, Yunfei Han, Guankai Qiu, Fantao Zhang, Jun Fang

2022, 49(9): 870-880. doi: 10.1016/j.jgg.2022.02.026

Abstract (247) PDF (48)

Abstract:
COMPASS or COMPASS-like is a highly conserved polyprotein complex in eukaryotes that is often involved in methylation of histone H3 lysine 4 (H3K4). However, the biological function of this complex in rice (Oryza sativa) is unclear. Here, we report the identifiction of their functions in growth and development. The osashl1 osashl2 double mutant shows a dwarf and late-flowering phenotype. Lower expression of Ehd1, OsVIL4, and OsMADS51 in the osashl1 osashl2 double mutant background accompanies a delayed vegetative growth phase and photoperiod-sensitive phase compared with that in wild type. Notably, there is less H3K4 mono-, di- and tri-methylation genome-wide in the double mutant, in particular less H3K4 tri-methylation at OsVIL4. Consistent with this result, knockout of OsVIL4 gives rise to a late-flowering phenotype similar to that of the osashl1 osashl2 double mutant, suggesting that OsVIL4 is a target of the COMPASS-like complex. In addition, the expression of key genes in brassinosteroid and gibberellic acid metabolism is altered in the osashl1 osashl2 double mutant, suggesting that the COMPASS-like complex regulates plant growth and development by modulating the levels of these two phytohormones. In summary, we demonstrate that OsASHL1 and OsASHL2 are important for floral transition and plant development.

Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis

Guodong Chen, Lin Han, Senwei Tan, Xiangbin Jia, Huidan Wu, Yingting Quan, Qiumeng Zhang, Bin Yu, Zhengmao Hu, Kun Xia, Hui Guo

2022, 49(9): 881-890. doi: 10.1016/j.jgg.2022.03.004

Abstract (420) PDF (60)

Abstract:
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that cause severe social, communication, and behavioral problems. Recent studies show that the variants of a histone methyltransferase gene KMT5B cause neurodevelopmental disorders (NDDs), including ASD, and the knockout of Kmt5b in mice is embryonic lethal. However, the detailed genotype-phenotype correlations and functional effects of KMT5B in neurodevelopment are unclear. By targeted sequencing of a large Chinese ASD cohort, analyzing published genome-wide sequencing data, and mining literature, we curated 39 KMT5B variants identified from NDD individuals. A genotype-phenotype correlation analysis for 10 individuals with KMT5B pathogenic variants reveals common symptoms, including ASD, intellectual disability, languages problem, and macrocephaly. In vitro knockdown of the expression of Kmt5b in cultured mouse primary cortical neurons leads to a decrease in neuronal dendritic complexity and an increase in dendritic spine density, which can be rescued by expression of human KMT5B but not that of pathogenic de novo missense mutants. In vivo knockdown of the Kmt5b expression in the mouse embryonic cerebral cortex by in utero electroporation results in decreased proliferation and accelerated migration of neural progenitor cells. Our findings reveal essential roles of histone methyltransferase KMT5B in neuronal development, prenatal neurogenesis, and neuronal migration.

Highly Regional Genes: graph-based gene selection for single-cell RNA-seq data

Yanhong Wu, Qifan Hu, Shicheng Wang, Changyi Liu, Yiran Shan, Wenbo Guo, Rui Jiang, Xiaowo Wang, Jin Gu

2022, 49(9): 891-899. doi: 10.1016/j.jgg.2022.01.004

Abstract (500) PDF (43)

Abstract:
Gene selection is an indispensable step for analyzing noisy and high-dimensional single-cell RNA-seq (scRNA-seq) data. Compared with the commonly used variance-based methods, by mimicking the human maker selection in the 2D visualization of cells, a new feature selection method called HRG (Highly Regional Genes) is proposed to find the informative genes, which show regional expression patterns in the cell-cell similarity network. We mathematically find the optimal expression patterns that can maximize the proposed scoring function. In comparison with several unsupervised methods, HRG shows high accuracy and robustness, and can increase the performance of downstream cell clustering and gene correlation analysis. Also, it is applicable for selecting informative genes of sequencing-based spatial transcriptomic data.

Pinpointing the animal origins of SARS-CoV-2: a genomic approach

Shilei Zhao, Yali Hou, Xiaolong Zhang, Alice Hughes, Na Liu, Minsheng Peng, Qihui Wang, Yongbiao Xue, Hua Chen

2022, 49(9): 900-902. doi: 10.1016/j.jgg.2022.05.002

Abstract (477) PDF (17)

Abstract:

Genome-wide analyses of nonsyndromic cleft lip with or without palate identify 20 new risk loci in the Chinese Han population

Bao Li, Liang Yong, Yafen Yu, Yanqin Yu, Qi Zhen, Huiyao Ge, Yiwen Mao, Weiwei Chen, Yanxia Yu, Yirui Wang, Zhuo Li, Wencheng Fan, Chang Zhang, Xia Hu, Ruixue Zhang, Lu Cao, Hao Liu, Zhuan Bian, Miao He, Liangdan Sun

2022, 49(9): 903-905. doi: 10.1016/j.jgg.2022.02.004

Abstract (334) PDF (51)

Abstract:

Building a cattle pan-genome using more de novo assemblies

Mian Gong, Peng Yang, Wenwen Fang, Ran Li, Yu Jiang

2022, 49(9): 906-908. doi: 10.1016/j.jgg.2022.01.003

Abstract (485) PDF (75)

Abstract:

Bmelo12, an elongase of very long-chain fatty acids gene, regulates silk yield in Bombyx mori

Weidong Zuo, Chunlin Li, Yanyu Liu, Rui Gao, Yue Luan, Bili Zhang, Hai Hu, Minjin Han, Xiaoling Tong, Cheng Lu, Fangyin Dai

2022, 49(9): 909-911. doi: 10.1016/j.jgg.2022.02.017

Abstract (362) PDF (43)

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2022 Vol. 49, No. 9