Journal of Genetics and Genomics

Massively parallel characterization of non-coding de novo mutations in autism spectrum disorder

Congcong Chen, Songwei Guo, et al.

doi: 10.1016/j.jgg.2025.07.008

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Abstract:
Autism spectrum disorder (ASD) is a neurodevelopmental disorder where de novo mutations play a significant role. Although coding mutations in ASD have been extensively characterized, the impact of non-coding de novo mutations (ncDNMs) remains less understood. Here, we integrate cortex cell-specific cis-regulatory element annotations, a deep learning-based variant prediction model, and massively parallel reporter assays to systematically evaluate the functional impact of 227,878 ncDNMs from Simons Simplex Collection (SSC) and Autism Speaks MSSNG resource (MSSNG) cohorts. Our analysis identifies 238 ncDNMs with confirmed functional regulatory effects, including 137 down-regulated regulatory mutations (DrMuts) and 101 up-regulated regulatory mutations (UrMuts). Subsequent association analyses reveal that only DrMuts regulating loss-of-function (LoF) intolerant genes rather than other ncDNMs are significantly associated with the risk of ASD (Odds ratio = 4.34; P = 0.001). A total of 42 potential ASD-risk DrMuts across 41 candidate ASD-susceptibility genes are identified, including 12 recognized and 29 unreported genes. Interestingly, these noncoding disruptive mutations tend to be observed in genes extremely intolerant to LoF mutations. Our study introduces an optimized approach for elucidating the functional roles of ncDNMs, thereby expanding the spectrum of pathogenic variants and deepening our understanding of the complex molecular mechanisms underlying ASD.

Universal single-copy ortholog benchmark gene set for bryophytes

Xuping Zhou, Tao Peng, et al.

doi: 10.1016/j.jgg.2025.07.009

Abstract (10) PDF (0)

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Functional characterization of OsLT9 in regulating rice leaf thickness

Jian Wang, Dagang Chen, et al.

doi: 10.1016/j.jgg.2025.07.010

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Abstract:
Leaf thickness in rice critically influences photosynthetic efficiency and yield, yet its genetic basis remains poorly understood, with few functional genes previously characterized. In this study, we employ a pangenome-wide association study (Pan-GWAS) on 302 diverse rice accessions from southern China, identifying 49 quantitative trait loci (QTLs) associated with leaf thickness. The most significant locus, qLT9, is fine-mapped to a 79 kb region on chromosome 9. Transcriptomic and genomic sequence analyses identify LOC_Os09g33480, which encodes a protein belonging to Multiple Organellar RNA Editing Factor (MORF) family, as the key candidate gene. Overexpression and complementation transgenic experiments confirm LOC_Os09g33480 (OsLT9) as the functional gene underlying qLT9, demonstrating a 24-bp Indel in its promoter correlates with the expression levels and leaf thickness. Notably, OsLT9 overexpression lines show not only thicker leaf, but also significantly enhanced photosynthetic efficiency and grain yield, establishing a link between leaf thickness modulation and yield enhancement. Population genomic analyses indicate strong selection for OsLT9 during domestication and breeding, with modern cultivars favoring thick leaf haplotype of OsLT9. This study establishes OsLT9 as a key regulator controlling leaf thickness in rice, and provides a valuable genetic resource for molecular breeding of high-yielding rice through optimization of plant architecture.

Postnatal critical-period brain plasticity and neurodevelopmental disorders: revisited circuit mechanisms

Ziwei Shang, Xiaohui Zhang

doi: 10.1016/j.jgg.2025.07.006

Abstract (19) PDF (0)

Abstract:
Critical periods (CPs) are defined as postnatal developmental windows during which brain circuits exhibit heightened sensitivity to altered experiences or sensory inputs, particularly during brain development in humans and animals. During the CP, experience-induced refinements of neural connections are crucial for establishing adaptive and mature brain functions, and aberrant CPs are often accompanied by many neurodevelopmental disorders (NDDs), including autism spectrum disorders and schizophrenia. Understanding neural mechanisms underlying the CP regulation is key to delineating the etiology of NDDs caused by abnormal postnatal neurodevelopment. Recent evidence from studies using innovative experimental tools has continuously revisited the inhibition-gating theory of CP to systematically elucidate the differential roles of distinct inhibitory circuits. Here, we provide a comprehensive review of classical experimental findings and emerging inhibitory-circuit regulation mechanisms of the CP, and further discuss how aberrant CP plasticity is associated with NDDs.

Jasmonate signaling: integrating stress responses with developmental regulation in plants

Yanbing Li, Fangming Wu, et al.

doi: 10.1016/j.jgg.2025.07.007

Abstract (24) PDF (0)

Abstract:
Jasmonates (JAs) are essential phytohormones that coordinate plant defense and development in response to unpredictable environments. Recent scientific advances have highlighted the SCF^COI1-JAZ-MYC2-MED25 module as a central hub for JA signaling, orchestrating transcriptional repression, derepression, activation, amplification, and feedback termination. This review summarizes current insights into the roles of JA in the regulation of biotic and abiotic stress responses and agronomic traits, including root development, regeneration, fertility, flowering, leaf senescence, and seed development, with a particular emphasis on the crosstalk between JA and a wound-induced peptide hormone, systemin, which mediates systemic wound responses. A deeper understanding of the JA regulatory mechanisms will provide valuable strategies for engineering crops with enhanced stress resilience and improved yields. We further propose JA-based strategies as a promising avenue for crop improvement.

Receptor-like protein 51 regulates brassinosteroid signaling by promoting the abundances of BRI1 and BAK1

Yuan Fang, Pengcheng Li, et al.

doi: 10.1016/j.jgg.2025.07.005

Abstract (18) PDF (0)

Abstract:
Brassinosteroids (BRs) are essential phytohormones that broadly regulate plant growth, development, and adaptation to biotic and abiotic stresses. In Arabidopsis, apoplastic BR molecules are perceived by a plasma membrane-localized receptor complex comprising the ligand-binding receptor BRI1 and the co-receptor BAK1. While negative regulators of the BR receptor complex, such as BKI1, BIR3, and PUB12/13, have been well characterized, how BRI1 and BAK1 are positively modulated in the BR pathway remains largely unknown. In this study, a genetic screen involving overexpression of RLP genes in the bak1-3 bkk1-1 double mutant reveals that enhanced RLP51 expression partially suppresses the BR-deficient phenotypes of bak1-3 bkk1-1. RLP51 overexpression also partially rescues the weak bri1 mutant allele, bri1-301. Although the rlp51 single mutant exhibits wild-type-like phenotypes, it enhances BR-defective phenotypes in bri1-301 and bak1 serk1 mutants. RLP51 is next found to interact with both BRI1 and BAK1 without affecting BRI1-BAK1 interaction. Critically, co-expression of RLP51 with BRI1 or BAK1 significantly increases BRI1 and BAK1 protein abundances. RLP51 appears to promote protein synthesis rather than stabilize BRI1 and BAK1 proteins. Thus, our study identifies RLP51 as a positive regulator of BR signaling that enhances the protein levels of BRI1 and BAK1.