Journal of Genetics and Genomics

Application of an optimized non-invasive prenatal testing for thalassemia based on change of haplotype doses

Fei Sun, Yao Zhou, et al.

doi: 10.1016/j.jgg.2025.09.007

Abstract (4) PDF (1)

Abstract:

Patients affected by monogenic diseases impose a substantial burden on both themselves and their families. The primary preventive measure, i.e., invasive prenatal diagnosis, carries a risk of miscarriage and cannot be performed early in pregnancy. Hence, there is a need for non-invasive prenatal testing (NIPT) for monogenic diseases. By utilizing enriched cell-free fetal DNA (cffDNA) from maternal plasma, we refine the NIPT method, which combines targeted region capture technology, haplotyping, and analysis of informative site frequency. We apply this method to 93 clinical families at genetic risk for thalassemia, encompassing various genetic variant types, to establish a workflow and evaluate its efficiency. Our approach requires only 3 ng of DNA input to generate 0.1 GB of informative target genomic data and leverages a minimum of 3% cffDNA. This method has a 98.16% success rate and 100% concordance with conventional invasive methods. Furthermore, we demonstrate the ability to analyze fetal genotypes as early as eight weeks of gestation. This study establishes an optimized NIPT method for the early detection of various thalassemia disorders during pregnancy. This technique demonstrates high accuracy and potential for clinical application in prenatal diagnosis.

A telomere-to-telomere genome assembly of the large yellow croaker provides insights into evolution of golden-yellow coloration

Shengyong Xu, Qi Liu, et al.

doi: 10.1016/j.jgg.2025.09.006

Abstract (8) PDF (0)

Abstract:
The large yellow croaker (Larimichthys crocea) is a flagship marine fish in China given its extreme commercial value and golden-yellow coloration. However, the genetic mechanisms underlying golden-yellow coloration remain unclear. Here, we construct a telomere-to-telomere gap-free genome assembly (T2T-Larcro_1.0) spanning 716.87 Mb, with a contig N50 of 31.75 Mb. Compared to the current reference genome (L_crocea_2.0), T2T-Larcro_1.0 incorporates 112.70 Mb of previously unassembled regions and 2368 newly anchored genes. This assembly facilitates comparative genomics analyses in sciaenids by identifying several candidate genes (e.g., OPNVA, nNOS, RDH13) potentially involved in evolution of golden-yellow coloration. Transcriptomic analyses further confirm expression of OPNVA-encoded vertebrate ancient opsin (VA opsin) in skin tissues of the large yellow croaker, suggesting its role as an extraretinal photoreceptor regulating localized golden-yellow coloration. Integrating genomics and transcriptomics results, our results uncover the triggering effect of VA opsin linking skin and neural photoreception to physiological regulation of body color change (golden-yellow to silvery-white) in L. crocea. Collectively, our findings provide molecular evidence that elucidate the underlying evolutionary mechanism of golden-yellow coloration in L. crocea. This high-quality genome assembly also serves as an improved resource for biological evolution, genetic improvement, and selective breeding of L. crocea.

Deep insights and clinical benefits from the comprehensive cohort of fetal skeletal dysplasia in China

Guozhuang Li, Kexin Xu, et al.

doi: 10.1016/j.jgg.2025.09.005

Abstract (8) PDF (0)

Abstract:
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 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.

The application and prospects of spatial omics technologies in clinical medical research and molecular diagnostics

Xiaofeng Wu, Weize Xu, et al.

doi: 10.1016/j.jgg.2025.09.003

Abstract (56) PDF (0)

Abstract:
While conventional FISH and IHC methods struggle to decode complex tissue heterogeneity and comprehensive molecular diagnosis due to low-throughput spatial information, spatial omics technologies enable high-throughput molecular mapping across tissue microenvironments. These technologies are emerging as transformative tools in molecular diagnostics and medical research. By integrating histopathological morphology with spatial multi-omics profiling (genome, transcriptome, epigenome, and proteome), spatial omics technologies open an avenue for understanding disease progression, therapeutic resistance mechanisms, and precise diagnosis. It particularly enhances tumor microenvironment analysis by mapping immune cell distributions and functional states, which may greatly facilitate tumor molecular subtyping, prognostic assessment, and predicting the efficacy of radiotherapy and chemotherapy. Despite the substantial advancements in spatial omics, the translation of spatial omics into clinical applications remains challenging due to robustness, efficacy, clinical validation, and cost constraints. In this review, we will summarize the current progress and prospects of spatial omics technologies, particularly in medical research and diagnostic applications.

Genome of aerial alga Trentepohlia odorata reveals insights into the evolution of terrestrial lifestyle in green algae

Yuanhao Li, Jiao Fang, et al.

doi: 10.1016/j.jgg.2025.09.004

Abstract (20) PDF (0)

Abstract:
Trentepohliales is a completely terrestrial order within Ulvophyceae (the core Chlorophyta), and its closely related lineages are mainly marine macroalgae (green seaweeds). Despite the considerable interest in their biotechnological potential, little is known about their adaptations to challenging terrestrial habitats. Here, we assemble the high-quality reference genome of Trentepohlia odorata. This alga shows duplications of key genes associated with lipid metabolism and carotenoid synthesis, potentially facilitating intracellular accumulation of lipid droplets and carotenoids. We further reveal positive selection and expansion of gene families involved in vesicle trafficking and cell division regulation in T. odorata compared to other algae (cleavage furrow-mediated cell division) in Ulvophyceae, providing a genetic foundation for the evolution of phragmoplast-mediated cell division. The combined C₄-like and biophysical carbon-concentrating mechanisms (CCMs) of T. odorata enable adaptation to fluctuating CO₂ environments, and support efficient photosynthesis under CO₂-limited conditions. Adaptive strategies of T. odorata to terrestrial stressors, such as drought, intense light, and UV-B radiation, include horizontally acquired genes involved in cell wall synthesis and remodeling, homeostasis of aldehydes, and expanded genes associated with reactive oxygen species (ROS), DNA repair, and photoprotection. Our study provides a valuable genomic resource for studying aerial algae and improves understanding of plant terrestrialization.

Genomic sequencing as a key primary recommendation for neonatal hyperbilirubinemia: a population-based multicenter study

Dabin Huang, Xia Gu, et al.

doi: 10.1016/j.jgg.2025.09.002

Abstract (21) PDF (0)

Abstract:
Genetic variations are risk factors for neonatal hyperbilirubinemia (NHB), a common cause of infant hospitalization in the first postnatal week, but their contribution and long-term impacts remain unclear. This population-based multicenter study enrolls 1,780 hospitalized NHB newborns and 38,158 genetically screened newborns across 20 hospitals (2019–2022). Excluding cases with clear clinical causes, 977 NHB cases are categorized into genetic variation-positive and -negative groups. Results show significantly higher NHB-related gene variants (81.63% vs. 65.62%) and positive variation rates (36.29% vs. 9.4%) in NHB cases than in the general newborn population (all P < 0.001). Among the 977 NHB cases, 325 (33.3%) have positive variants, with higher rates of severe hyperbilirubinemia (16.9% vs. 9.7%, P = 0.001), prolonged jaundice (36.3% vs. 27.6%, P = 0.005), and cholestasis/hypercholanaemia (23.7% vs. 14.7%, P < 0.001) in the positive group. Cumulative genetic variants in bilirubin metabolism pathways exhibit dose-dependent associations with increased risks of complications. Long-term follow-up reveals that UGT1A1 variants prolong jaundice up to 1 month, while severe SLC10A1 variants cause persistent cholestasis/hypercholanaemia beyond 9 months. This large-scale evidence highlights genetic factors as key NHB determinants, with implications for neonatal care protocols to integrate genetic testing and establish long-term surveillance for variant carriers.