Journal of Genetics and Genomics

eQTL studies: from bulk tissues to single cells

Jingfei Zhang, Hongyu Zhao

2023, 50(12): 925-933. doi: 10.1016/j.jgg.2023.05.003

Abstract (176) PDF (12)

Abstract:
An expression quantitative trait locus (eQTL) is a chromosomal region where genetic variants are associated with the expression levels of specific genes that can be both nearby or distant. The identifications of eQTLs for different tissues, cell types, and contexts have led to a better understanding of the dynamic regulations of gene expressions and implications of functional genes and variants for complex traits and diseases. Although most eQTL studies have been performed on data collected from bulk tissues, recent studies have demonstrated the importance of cell-type-specific and context-dependent gene regulations in biological processes and disease mechanisms. In this review, we discuss statistical methods that have been developed to enable the detection of cell-type-specific and context-dependent eQTLs from bulk tissues, purified cell types, and single cells. We also discuss the limitations of the current methods and future research opportunities.

Humoral and cellular immunity against diverse SARS-CoV-2 variants

Changxu Chen, Xin Wang, Zeli Zhang

2023, 50(12): 934-947. doi: 10.1016/j.jgg.2023.10.003

Abstract (0) PDF (0)

Abstract:
Since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has rapidly spread worldwide. This has led to an unprecedented global pandemic, marked by millions of COVID-19 cases and a significant number of fatalities. Over a relatively short period, several different vaccine platforms are developed and deployed for use globally to curb the pandemic. However, the genome of SARS-CoV-2 continuously undergoes mutation and/or recombination, resulting in the emergence of several variants of concern (VOC). These VOCs can elevate viral transmission and evade the neutralizing antibodies induced by vaccines, leading to reinfections. Understanding the impact of the SARS-CoV-2 genomic mutation on viral pathogenesis and immune escape is crucial for assessing the threat of new variants to public health. This review focuses on the emergence and pathogenesis of VOC, with particular emphasis on their evasion of neutralizing antibodies. Furthermore, the memory B cell, CD4⁺, and CD8⁺ T cell memory induced by different COVID-19 vaccines or infections are discussed, along with how these cells recognize VOC. This review summarizes the current knowledge on adaptive immunology regarding SARS-CoV-2 infection and vaccines. Such knowledge may also be applied to vaccine design for other pathogens.

Protein O-GlcNAcylation homeostasis regulates facultative heterochromatin to fine-tune sog-Dpp signaling during Drosophila early embryogenesis

Yaowen Zhang, Haibin Yu, Dandan Wang, Xiaoyun Lei, Yang Meng, Na Zhang, Fang Chen, Lu Lv, Qian Pan, Hongtao Qin, Zhuohua Zhang, Daan M. F. van Aalten, Kai Yuan

2023, 50(12): 948-959. doi: 10.1016/j.jgg.2023.05.014

Abstract (120) PDF (20)

Abstract:
Protein O-GlcNAcylation is a monosaccharide post-translational modification maintained by two evolutionarily conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Mutations in human OGT have recently been associated with neurodevelopmental disorders, although the mechanisms linking O-GlcNAc homeostasis to neurodevelopment are not understood. Here, we investigate the effects of perturbing protein O-GlcNAcylation using transgenic Drosophila lines that overexpress a highly active OGA. We reveal that temporal reduction of protein O-GlcNAcylation in early embryos leads to reduced brain size and olfactory learning in adult Drosophila. Downregulation of O-GlcNAcylation induced by the exogenous OGA activity promotes nuclear foci formation of Polycomb-group protein Polyhomeotic and the accumulation of excess K27 trimethylation of histone H3 (H3K27me3) at the mid-blastula transition. These changes interfere with the zygotic expression of several neurodevelopmental genes, particularly short gastrulation (sog), a component of an evolutionarily conserved sog-Decapentaplegic (Dpp) signaling system required for neuroectoderm specification. Our findings highlight the importance of early embryonic O-GlcNAcylation homeostasis for the fidelity of facultative heterochromatin redeployment and initial cell fate commitment of neuronal lineages, suggesting a possible mechanism underpinning OGT-associated intellectual disability.

Inhibition of the maize salt overly sensitive pathway by ZmSK3 and ZmSK4

Jianfang Li, Xueyan Zhou, Yan Wang, Shu Song, Liang Ma, Qian He, Minhui Lu, Kaina Zhang, Yongqing Yang, Qian Zhao, Weiwei Jin, Caifu Jiang, Yan Guo

2023, 50(12): 960-970. doi: 10.1016/j.jgg.2023.04.010

Abstract (207) PDF (52)

Abstract:
Soil salinity is a worldwide problem that adversely affects plant growth and crop productivity. The salt overly sensitive (SOS) pathway is evolutionarily conserved and essential for plant salt tolerance. In this study, we reveal how the maize shaggy/glycogen synthase kinase 3-like kinases ZmSK3 and ZmSK4, orthologs of brassinosteroid insensitive 2 in Arabidopsis thaliana, regulate the maize SOS pathway. ZmSK3 and ZmSK4 interact with and phosphorylate ZmSOS2, a core member of the maize SOS pathway. The mutants defective in ZmSK3 or ZmSK4 are hyposensitive to salt stress, with higher salt-induced activity of ZmSOS2 than that in the wild type. Furthermore, the Ca²⁺ sensors ZmSOS3 and ZmSOS3-like calcium binding protein 8 (ZmSCaBP8) activate ZmSOS2 to maintain Na⁺/K⁺ homeostasis under salt stress and may participate in the regulation of ZmSOS2 by ZmSK3 and ZmSK4. These findings discover the regulation of the maize SOS pathway and provide important gene targets for breeding salt-tolerant maize.

Genetic interrogation of phenotypic plasticity informs genome-enabled breeding in cotton

Yuefan Huang, Zhengyang Qi, Jianying Li, Jiaqi You, Xianlong Zhang, Maojun Wang

2023, 50(12): 971-982. doi: 10.1016/j.jgg.2023.05.004

Abstract (161) PDF (17)

Abstract:
Phenotypic plasticity, or the ability to adapt to and thrive in changing climates and variable environments, is essential for developmental programs in plants. Despite its importance, the genetic underpinnings of phenotypic plasticity for key agronomic traits remain poorly understood in many crops. In this study, we aim to fill this gap by using genome-wide association studies to identify genetic variations associated with phenotypic plasticity in upland cotton (Gossypium hirsutum L.). We identified 73 additive quantitative trait loci (QTLs), 32 dominant QTLs, and 6799 epistatic QTLs associated with 20 traits. We also identified 117 additive QTLs, 28 dominant QTLs, and 4691 epistatic QTLs associated with phenotypic plasticity in 19 traits. Our findings reveal new genetic factors, including additive, dominant, and epistatic QTLs, that are linked to phenotypic plasticity and agronomic traits. Meanwhile, we find that the genetic factors controlling the mean phenotype and phenotypic plasticity are largely independent in upland cotton, indicating the potential for simultaneous improvement. Additionally, we envision a genomic design strategy by utilizing the identified QTLs to facilitate cotton breeding. Taken together, our study provides new insights into the genetic basis of phenotypic plasticity in cotton, which should be valuable for future breeding.

PIFs interact with SWI2/SNF2-related 1 complex subunit 6 to regulate H2A.Z deposition and photomorphogenesis in Arabidopsis

Huiru Chen, Wanting Wang, Xiao Chen, Yake Niu, Yuanyuan Qi, Ze Yu, Minyu Xiong, Pengbo Xu, Wenxiu Wang, Tongtong Guo, Hong-Quan Yang, Zhilei Mao

2023, 50(12): 983-992. doi: 10.1016/j.jgg.2023.04.008

Abstract (278) PDF (56)

Abstract:
Light is an essential environmental signal perceived by a broad range of photoreceptors in plants. Among them, the red/far-red light receptor phytochromes function to promote photomorphogenesis, which is critical to the survival of seedlings after seeds germination. The basic-helix-loop-helix transcription factors phytochrome-interacting factors (PIFs) are the pivotal direct downstream components of phytochromes. H2A.Z is a highly conserved histone variant regulating gene transcription, and its incorporation into nucleosomes is catalyzed by SWI2/SNF2-related 1 complex, in which SWI2/SNF2-related 1 complex subunit 6 (SWC6) and actin-related protein 6 (ARP6) serve as core subunits. Here, we show that PIFs physically interact with SWC6 in vitro and in vivo, leading to the disassociation of HY5 from SWC6. SWC6 and ARP6 regulate hypocotyl elongation partly through PIFs in red light. PIFs and SWC6 coregulate the expression of auxin-responsive genes such as IAA6, IAA19, IAA20, and IAA29 and repress H2A.Z deposition at IAA6 and IAA19 in red light. Based on previous studies and our findings, we propose that PIFs inhibit photomorphogenesis, at least in part, through repression of H2A.Z deposition at auxin-responsive genes mediated by the interactions of PIFs with SWC6 and promotion of their expression in red light.

Natural variation in the SVP contributes to the pleiotropic adaption of Arabidopsis thaliana across contrasted habitats

Xiang Guo, Ruyun Liang, Shangling Lou, Jing Hou, Liyang Chen, Xin Liang, Xiaoqin Feng, Yingjun Yao, Jianquan Liu, Huanhuan Liu

2023, 50(12): 993-1003. doi: 10.1016/j.jgg.2023.08.004

Abstract (162) PDF (22)

Abstract:
Coordinated plant adaptation involves the interplay of multiple traits driven by habitat-specific selection pressures. Pleiotropic effects, wherein genetic variants of a single gene control multiple traits, can expedite such adaptations. Until present, only a limited number of genes have been reported to exhibit pleiotropy. Here, we create a recombinant inbred line (RIL) population derived from two Arabidopsis thaliana (A. thaliana) ecotypes originating from divergent habitats. Using this RIL population, we identify an allelic variation in a MADS-box transcription factor, SHORT VEGETATIVE PHASE (SVP), which exerts a pleiotropic effect on leaf size and drought-versus-humidity tolerance. Further investigation reveals that a natural null variant of the SVP protein disrupts its normal regulatory interactions with target genes, including GRF3, CYP707A1/3, and AtBG1, leading to increased leaf size, enhanced tolerance to humid conditions, and changes in flowering time of humid conditions in A. thaliana. Remarkably, polymorphic variations in this gene have been traced back to early A. thaliana populations, providing a genetic foundation and plasticity for subsequent colonization of diverse habitats by influencing multiple traits. These findings advance our understanding of how plants rapidly adapt to changing environments by virtue of the pleiotropic effects of individual genes on multiple trait alterations.

Zebrafish ppp1r21 mutant as a model for the study of primary biliary cholangitis

Chaoying Wu, Wenfeng Zhang, Yiyu Luo, Chaoqing Cheng, Xinjuan Wang, Yan Jiang, Shuang Li, Lingfei Luo, Yun Yang

2023, 50(12): 1004-1013. doi: 10.1016/j.jgg.2023.05.013

Abstract (161) PDF (11)

Abstract:
Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease that progresses to fibrosis and cirrhosis, resulting from the gradual destruction of intrahepatic bile ducts. Exploring genetic variants associated with PBC is essential to understand the pathogenesis of PBC. Here we identify a zebrafish balloon dog (blg) mutant with intrahepatic bile duct branching defects, exhibiting several key pathological PBC-like features, including immunodominant autoantigen PDC-E2 production, cholangiocyte apoptosis, immune cell infiltration, inflammatory activation, and liver fibrosis. blg encodes the protein phosphatase 1 regulatory subunit 21 (Ppp1r21), which is enriched in the liver and its peripheral tissues and plays a vital role in the early intrahepatic bile duct formation stage. Further studies show an excessive activation of the PI3K/AKT/mTOR pathway in the hepatic tissues in the mutant, while treatment with the pathway inhibitor LY294002 and rapamycin partially rescues intrahepatic bile duct branching defects and alleviates the PBC-like symptoms. These findings implicate the potential role of the Ppp1r21-mediated PI3K/AKT/mTOR pathway in the pathophysiology of PBC.

Gain of function screen of PATs reveals an essential role of Hip14 in Drosophila host defense

Zhu Deng, Hui Chen, Lingling Xiao, Haolan Jin, Qinhao Zhang, Renjie Jiao, Chuanxian Wei

2023, 50(12): 1014-1017. doi: 10.1016/j.jgg.2023.06.003

Abstract (227) PDF (21)

Abstract:

GAN-GMHI: a generative adversarial network with high discriminative power for microbiome-based disease prediction

Yuxue Li, Gang Xie, Yuguo Zha, Kang Ning

2023, 50(12): 1026-1028. doi: 10.1016/j.jgg.2023.03.009

Abstract (188) PDF (15)

Abstract:

Systematic identification and screening of functional long noncoding RNAs during planarian regeneration

Baijie Jin, Nannan Li, Lina Pang, Jing Xiao, Ziyi Lin, Ning Li, Zimei Dong, Guangwen Chen, Fei Yu, Dezeng Liu

2023, 50(12): 1018-1021. doi: 10.1016/j.jgg.2023.08.003

Abstract (259) PDF (11)

Abstract:

ABE-induced PDGFD start codon silencing unveils new insights into the genetic architecture of sheep fat tails

Peter Kalds, Shuhong Huang, Shiwei Zhou, Siyuan Xi, Yumeng Fang, Yawei Gao, Kexin Sun, Chao Li, Bei Cai, Yao Liu, Yige Ding, Qifang Kou, Tad Sonstegard, Björn Petersen, Stephen Kemp, Baohua Ma, Jian-Lin Han, Yulin Chen, Xiaolong Wang

2023, 50(12): 1022-1025. doi: 10.1016/j.jgg.2023.07.008

Abstract (232) PDF (24)

Abstract:

2023 Vol. 50, No. 12