Journal of Genetics and Genomics最新文献

Fetal skeletal dysplasia (FSD) encompasses diverse clinical features and complicates prenatal diagnosis and perinatal care. In this retrospective study, we integrate prenatal deep phenotyping with exome or genome sequencing (ES/GS) to elucidate comprehensive genotype and phenotype landscapes, diagnostic outcomes, genotype-phenotype correlations, and postnatal follow-up findings and to refine genetic counseling and clinical decision-making. The study includes a cohort of 152 fetuses with FSD in China. All fetuses undergo prenatal deep phenotyping followed by ES/GS analysis. Prenatal deep phenotyping enables classification into isolated and non-isolated FSD groups and identifies previously unrecognized prenatal features associated with KBG syndrome and Segawa syndrome. Among skeletal anomalies, limb bone anomalies are the most common (72.4%). Genetic testing yields positive diagnoses in 88 fetuses (57.9%). Notably, fetuses with cranial and limb bone abnormalities demonstrate a higher diagnostic yield. Comparative analysis of prenatal and postnatal genotypes and phenotypes in individuals harboring pathogenic variants in four hotspot genes provides a deeper understanding of skeletal dysplasia phenotypes. Genetic findings from this cohort directly inform reproductive decisions in 16 subsequent pregnancies. Our findings significantly enhance genotype-phenotype correlations and contribute to improved prenatal counseling, informed clinical decision-making, and optimized perinatal care, and advance precision medicine strategies for FSD-affected families.

Hawthorn (Crataegus pinnatifida) fruit peel color and seed hardness are key traits that significantly impact economic value. We present here the high-quality chromosome-scale genomes of two cultivars, including the hard-seed, yellow-peel C. pinnatifida "Jinruyi" (JRY) and the soft-seed, red-peel C. pinnatifida "Ruanzi" (RZ). The assembled genomes comprising 17 chromosomes are 809.1 Mb and 760.5 Mb in size, achieving scaffold N50 values of 48.5 Mb and 46.8 Mb for JRY and RZ, respectively. Comparative genomic analysis identifies 3.6-3.8 million single nucleotide polymorphisms, 8.5-9.3 million insertions/deletions, and approximately 30 Mb of presence/absence variations across different hawthorn genomes. Through integrating differentially expressed genes and accumulated metabolites, we filter candidate genes CpMYB114 and CpMYB44 associated with differences in hawthorn fruit peel color and seed hardness, respectively. Functional validation confirms that CpMYB114-CpANS regulates anthocyanin biosynthesis in hawthorn peels, contributing to the observed variation in peel color. CpMYB44-CpCOMT is significantly upregulated in JRY and has been shown to promote lignin biosynthesis, resulting in the distinction in seed hardness. Overall, this study reveals new insights into understanding of distinct peel pigmentation and seed hardness in hawthorn and provides an abundant resource for molecular breeding.

Seed size is an important agronomic trait determining crop yield. Identifying key genes involved in seed size regulation and elucidating their molecular mechanisms are of great significance for crop breeding. Recent studies in crops have uncovered numerous genes that control seed size and weight, many of which function by modulating phytohormone biosynthesis, metabolism, or signaling pathways. This review provides a comprehensive overview of the genetic and molecular mechanisms by which phytohormones regulate seed size and weight and their cross-talks in modulating seed size. We highlight the functional conservation and divergence of homologous genes that control seed size across species. A particular focus is placed on those genes that have promising potential for yield improvement. Finally, we discuss current challenges in phytohormone regulation of seed size and molecular design breeding strategies for translating this knowledge into crop improvement.

Understanding genetic variant functionality is essential for advancing animal genomics and precision breeding. However, the lack of comprehensive functional genomic annotations in animals limits the effectiveness of most variant function assessment methods. In this study, we gather 1030 raw epigenomic datasets from 10 animal species and systematically annotate 7 types of key regulatory regions, creating a comprehensive functional annotation map of animal genomic variants. Our findings demonstrate that integrating variants with regulatory annotations can identify tissues and cell types underlying economic traits, underscoring the utility of these annotations in functional variant discovery. Using our functional annotations, we rank the functional potential of genetic variants and classify over 127 million candidate variants into 5 functional confidence categories, with high-confidence variants significantly enriched in eQTLs and trait-associated SNPs. Incorporating these variants into genomic prediction models can improve estimated breeding value accuracy, demonstrating their practical utility in breeding programs. To facilitate the use of our results, we develop the Integrated Functional Mutation (IFmut: http://www.ifmutants.com:8212) platform, enabling researchers to explore regulatory annotations and assess the functional potential of animal variants efficiently. Our study provides a robust framework for functional genomic annotations in farm animals, enhancing variant function assessment and breeding precision.

Wheat is an important cereal crop used to produce diverse and popular food worldwide because of its high grain yield (GY) and grain protein content (GPC). However, GY and GPC are usually negatively correlated. We previously reported that favorable alleles of the wheat domestication gene Q can synchronously increase GY and GPC, but the underlying mechanisms remain largely unknown. In this study, we investigate the regulatory network involving Q associated with GY and GPC in young grains through DNA affinity purification sequencing and transcriptome sequencing analyses, electrophoretic mobility shift and dual-luciferase assays, and transgenic approaches. Three Q-binding motifs, namely TTAAGG, AAACA[A/T]A, and GTAC[T/G]A, are identified. Notably, genes related to photosynthesis or carbon and nitrogen metabolism are enriched and regulated by Q. Moreover, Q is revealed to bind directly to its own gene and the glutamine synthetase gene GSr-4D to increase expression, thereby influencing nitrogen assimilation during the grain filling stage and increasing GPC. Considered together, our findings provide molecular evidence of the positive regulatory effects of Q on wheat GY and GPC.

LIM zinc finger domain containing 1 (LIMS1), an evolutionarily conserved LIM domain adaptor protein, is implicated in diverse pathologies, including cancer and neurological disorders. However, its roles in cardiac diseases and the underlying mechanisms remain unclear. Here, we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure. We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes, suggesting that LIMS1 dysregulation contributes to cardiac pathology. Using CRISPR/Cas9 technology, we generate a zebrafish model of lims1 loss-of-function mutant, which exhibits severe cardiac chamber remodeling, systolic dysfunction, and premature mortality, demonstrating the essential role of lims1 in maintaining cardiac integrity. Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts. Strikingly, pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes. Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation, offering insights into cardiac remodeling and potential therapeutic strategies.

Primary cilia, microtubule-based organelles widely existing on eukaryotic cells, play a critical, indispensable role in the development and functional maintenance of the central nervous system (CNS). Here, we summarize recent advances on the distribution of primary cilia across different regions of the CNS, providing a detailed map highlighting their presence on both neurons and glial cells. Furthermore, we elaborate on the roles of primary cilia in essential physiological functions, including progenitor cell proliferation, neurogenesis, neuronal migration, and synaptic connections within the CNS. We also discuss the emerging links between ciliary dysfunction and a range of CNS disorders, including cognitive impairment, metabolic disorders and hyperphagia-induced obesity, neurodegenerative diseases, and psychiatric conditions. Integrating existing findings, this review provides a panoramic perspective on ciliary roles in the CNS and lays a critical foundation for subsequent basic research, disease-mechanism studies, and therapeutic-target exploration.

Human reproduction requires the fertilization of a mature oocyte with a sperm to form a high-quality embryo. Oogenesis, folliculogenesis, and the activities of the endocrine system play essential roles in female fertility, and disturbances in these processes can result in female infertility, which has become an urgent public health issue worldwide. Genetic studies have identified multiple variants in key genes underlying these processes in infertile females, and these patients are mainly diagnosed with disorders of sex development, premature ovarian insufficiency, congenital hypogonadotropic hypogonadism, central precocious puberty, resistant ovary syndrome, oocyte maturation arrest, fertilization failure, and early embryonic defects. Notably, the known genes account for about 13.2% cases of oocyte and embryo defects (479/3627) and 18.7% cases of premature ovarian insufficiency (193/1030). Here, we review the critical events in female reproduction and highlight the single gene variants with Mendelian inheritance patterns that are responsible for female infertility.