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[学术文献 ] Generation of transchromosomic mice harboring HLA-A/B/C and human B2M via mouse artificial chromosome and triple BAC integration 进入全文
Scientific Reports
Humanized transgenic mice carrying human genes are useful for research on gene function and disease. Bacterial artificial chromosomes (BACs) that carry human genomic sequences with regulatory elements enable the expression of transgenes at physiological levels in vivo. To study complex biological phenomena involving multiple genes, techniques for co-introducing transgenes into mice have been developed; however, the introduction of multiple BACs remains laborious. The simultaneous integration of multiple gene loading vectors (SIM) system was developed to incorporate three or more gene-loading vectors (GLVs) using a mouse artificial chromosome (MAC) vector. This system allows for simultaneous site-specific incorporation of three GLVs into a single MAC with only one screening. However, the capacity for large constructs, such as BACs, has yet to be evaluated. This study is the first to demonstrate the development of multi-BAC transchromosomic (Tc) mice targeting the human leukocyte antigen (HLA) class I gene cluster (HLA-A, HLA-B, HLA-C) and beta-2-microglobulin (B2M) using the SIM system. By constructing a MAC using three BACs containing these genomic regions, we successfully generated HLA class I Tc mice. The technology to generate multi-BAC Tc mice will accelerate the analysis of complex life mechanisms involving multiple factors.
[学术文献 ] Integrated biotechnological and AI innovations for crop improvement 进入全文
Nature
Crops provide food, clothing and other important products for the global population. To meet the demands of a growing population, substantial improvements are required in crop yield, quality and production sustainability. However, these goals are constrained by various environmental factors and limited genetic resources. Overcoming these limitations requires a paradigm shift in crop improvement by fully leveraging natural genetic diversity alongside biotechnological approaches such as genome editing and the heterologous expression of designed proteins, coupled with multimodal data integration. In this Review, we provide an in-depth analysis of integrated uses of omics technologies, genome editing, protein design and high-throughput phenotyping, in crop improvement, supported by artificial intelligence-enabled tools. We discuss the emerging applications and current challenges of these technologies in crop improvement. Finally, we present a perspective on how elite alleles generated through these technologies can be incorporated into the genomes of existing and de novo domesticated crops, aided by a proposed artificial intelligence model. We suggest that integrating these technologies with agricultural practices will lead to a new revolution in crop improvement, contributing to global food security in a sustainable manner.
[学术文献 ] Delineating genotype × environment interaction for horticultural traits in tomato using GGE and AMMI biplot analysis 进入全文
Nature
The aim of this study was to identify stable tomato hybrids for cultivation in India. The genotype-by-environment (G × E) interaction analysis was performed using GGE and AMMI biplots. Fifteen hybrids including two checks were grown in nine environments during winter, summer, and rainy seasons from 2021 to 2024 at Varanasi. G × E interaction was investigated for days to first harvesting, average fruit weight, pericarp thickness, total soluble solids (TSS), yield, and resistance to tomato leaf curl virus disease (ToLCD). The GGE biplot analysis identified stable and superior hybrids as well as ideal environments, based on mean vs. stability, which-won-where, discriminativeness vs. representativeness, genotype by trait (GT), genotype by yield × trait (GYT), and multi-trait genotype-ideotype distance index (MGIDI). As a result, we identified stable hybrids such as VRTH-16-4 (G2) and VRTH-16-3 (G1) for yield; VRTH-16-70 (G5) and VRTH-19-18 (G11) for days to first harvesting; VRTH-16-5 (G3) and VRTH-16-8 (G4) for fruit weight; VRTH-16-8 (G4) and VRTH-16-5 (G3) for pericarp thickness; VRTH-16-75 (G6) and VRTH-18-26 (G8) for TSS; and VRTH-16-5 (G3) and VRTH-16-70 (G5) for ToLCD resistance. Overall, this study highlights that tomato hybrids VRTH-16-4, VRTH-16-90, and VRTH-18-46 have potential for cultivation during heat and cool weather conditions.
[学术文献 ] Super-pangenome analyses across 35 accessions of 23 Avena species highlight their complex evolutionary history and extensive genomic diversity 进入全文
Nature Genetics
Common oat, belonging to the genus Avena with 30 recognized species, is a nutritionally important cereal crop and high-quality forage worldwide. Here, we construct a genus-level super-pangenome of Avena comprising 35 high-quality genomes from 14 cultivated oat accessions and 21 wild species. The fully resolved phylogenomic analysis unveils the origin and evolutionary scenario of Avena species, and the super-pangenome analysis identifies 26.62% and 59.93% specific genes and haplotypes in wild species. We delineate the landscape of structural variations (SVs) and the transcriptome profile based 1,401 RNA-sequencing (RNA-seq) samples from diverse abiotic stress treatments in oat. We highlight the crucial role of SVs in modulating gene expression and shaping adaptation to diverse stresses. Further combining SV-based genome-wide association studies (GWASs), we characterize 13 candidate genes associated with drought resistance such as AsARF7, validated by transgenic oat lines. Our study provides unprecedented genomic resources to facilitate genomic, evolution and molecular breeding research in oat.
[学术文献 ] Regulation of MORC-1 is key to the CSR-1–mediated germline gene licensing mechanism in C. elegans 进入全文
Science Advances
The Argonaute CSR-1 is essential for germline development in C. elegans. Loss of CSR-1 leads to the down-regulation of thousands of germline-expressed genes, supporting a model in which CSR-1 “licenses” gene expression via a poorly understood mechanism. In contrast, a small subset of genes is up-regulated in csr-1 mutants, including morc-1, which encodes a conserved GHKL-type ATPase. We show that morc-1 is overexpressed in csr-1 mutants and accumulates over CSR-1 licensed targets, coinciding with aberrant gain of H3K9me3, reduced H3K36me3, and transcriptional repression. Notably, loss of morc-1 fully rescues these chromatin defects and partially restores gene expression and fertility in csr-1 mutants. Conversely, ectopic overexpression of MORC-1 in the wild-type germ line is sufficient to repress CSR-1 licensed targets and severely compromise fertility. These findings support a model in which CSR-1 prevents MORC-1 overexpression and consequent misregulation of CSR-1 licensed genes.
[前沿资讯 ] Predicting expression-altering promoter mutations with deep learning 进入全文
Science
Only a minority of patients with rare genetic diseases are presently diagnosed by exome sequencing, suggesting that additional unrecognized pathogenic variants may reside in noncoding sequence. In this work, we describe PromoterAI, a deep neural network that accurately identifies noncoding promoter variants that dysregulate gene expression. We show that promoter variants with predicted expression-altering consequences produce outlier expression at both the RNA and protein levels in thousands of individuals and that these variants experience strong negative selection in human populations. We observed that clinically relevant genes in patients with rare diseases are enriched for such variants and validated their functional impact through reporter assays. Our estimates suggest that promoter variation accounts for 6% of the genetic burden associated with rare diseases.
