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At least 19 recordsLinked to original sources

PubMed2025

Candidate genes at the Rmi1 locus for resistance to Meloidogyne incognita in soybean.

The RKN resistance locus Rmi1 was fine-mapped to two genes on chromosome 10, a glycosyl hydrolase family 9 β-1,4-endoglucanase gene and a type I pectin methylesterase gene. Root-knot nematodes (Meloidogyne spp.) are a serious threat to soybean production in the southeast USA, with yield losses of more than $165 million in 2023. Development and deployment of resistant soybean cultivars is the most effective strategy for managing these nematode pests; however, the identity of the resistance genes and underlying mechanism of resistance remains obscure. An additive resistance gene, Resistance to M. incognita-1 (Rmi1), to the predominant species, was first identified in soybean cultivar Forrest but never mapped to a genomic region. Multiple mapping studies have identified a major quantitative trait locus (QTL) with additive action on chromosome 10. In this study, a population consisting of 170 F2:3 families derived from a cross of Bossier (susceptible) × Forrest (resistant) was initially used to confirm that Rmi1 is in the chromosome 10 QTL. Subsequently, 884 F5:6 recombinant inbred lines (RILs) derived from the same cross were used to fine-map the Rmi1 causal gene(s) to two genes - a β-1,4-endoglucanase (Glyma.10G017000, EG) and a pectin methylesterase/methylesterase inhibitor (Glyma.10G017100, PME1). Both gene candidates have the potential to play a role in the resistance response to M. incognita. Both gene promoters harbor SNPs and indels and the encoded proteins exhibit amino acid polymorphisms, including a premature stop in PME1 of resistant soybeans. Additionally, both genes show a higher expression level in susceptible roots compared to resistant roots in the absence of infection. This suggests that Rmi1 may confer one or more pre-existing differences related to cell wall modification in soybean roots, ultimately leading to a decrease in susceptibility.

Tylenchoidea↗

PubMed2026

Genome-wide identification and expression profiling of CSP and OBP genes in Stictocephala bisonia reveals candidate genes potentially associated with insecticide response.

Stictocephala bisonia is an important invasive agricultural pest. Due to the frequent application of insecticides in its habitat, this species is under intense selection pressure. Chemosensory proteins (CSPs) and odorant-binding proteins (OBPs) are known to play key roles in insecticide resistance, but their specific functions in S. bisonia remain unclear. In this study, we identified a total of 22 SbisCSPs and 16 SbisOBPs based on the S. bisonia genome. To screen for candidate genes potentially linked to insecticide resistance, we adopted a multi-criteria screening strategy that integrated phylogenetic analysis, molecular docking with three insecticides, and tissue-specific expression profiling. Phylogenetic analysis identified several SbisCSPs and SbisOBPs clustering with genes known to be involved in insecticide resistance, serving as an initial evolutionary filter. Molecular docking results indicated that λ-Cyhalothrin exhibited the strong predicted binding affinity with most of SbisCSPs and SbisOBPs. Subsequent qPCR validation of seven prioritized candidates revealed distinct expression patterns: SbisCSP22 was highly expressed in adults and demonstrated strong binding affinity to all three insecticides tested, suggesting a potential role in mediating multi-insecticide response. Conversely, SbisCSP17 was significantly upregulated in larvae, clustered with genes known to mediate imidacloprid resistance, and exhibited strong binding affinity to imidacloprid. Given its larval-specific expression and the soil-dwelling behavior of larvae, we hypothesize that SbisCSP17 is a key candidate gene for larvae coping with soil-treated insecticides.

Animals↗

PubMed2025

Differential gene expression study in whole blood identifies candidate genes for psychosis in African American individuals.

Genome-wide association has identified regions of the genome that mediate risk for psychosis. It is possible that variants in these regions confer risk by altering gene expression. This work has predominantly been conducted in individuals of European descent and has focused narrowly on schizophrenia rather than psychosis as a syndrome. In the present study we investigated alterations in gene expression in African American individuals with a range of psychotic diagnoses to increase understanding of the etiology in an underserved population. We performed RNA-seq in whole bloody to survey the transcriptome in 126 patients with a psychosis-spectrum disorder and 217 healthy controls and applied differential gene expression analyses across the genome while controlling for age, sex, population stratification and batch. We found 18 differentially expressed genes (DEGs), some of the locations of the corresponding genes overlap with previously implicated regions for psychosis, but many of which were novel associations. Enrichment analysis of nominally significant genes (p < 0.05) revealed overrepresentation of biological processes relating to platelet, immune and cellular function, and sensory perception. Weighted gene co-expression network analysis, applied to identify modules of co-expressed genes associated with psychosis, revealed 10 modules, one of which was significantly associated with psychosis. This module was significantly enriched for DEGs, and for platelet function. These results support the potential role of immune function in the etiology of psychosis, identify novel candidate gene expression phenotypes that correspond to both established and new genomic regions, in individuals of African American ancestry.

Humans↗

PubMed2025

Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families.

PURPOSE: Congenital anomalies of the kidney and urinary tract (CAKUT) encompass heterogenous malformations arising from defective nephrogenesis. To date, approximately 50 monogenic genes are known to cause CAKUT if mutated. Recent studies show the impact of de novo variants in genetic disease etiology. Trio exome sequencing identifies de novo variants in novel candidate genes in 19.62% of CAKUT families. METHODS: We performed trio-based exome sequencing in 209 families with CAKUT to detect novel candidate disease genes. RESULTS: Trio analysis yielded in the identification of CAKUT candidate genes in 96 of 209 trio families (45.93%). In 41 of 209 cases, we detected strong de novo variants in 45 potential novel CAKUT candidate genes (19.62%). We developed a prioritization approach that highlights a truncating de novo variant in SOX13 (HGNC:11192) as a promising cause for CAKUT. In addition, further allele carriers for the candidate gene CHD1L (HGNC:1916) were identified, thus supporting the role of CHD1L in the pathogenesis of CAKUT. CONCLUSION: We conclude that de novo variants in potential novel CAKUT candidate genes contribute to the disease etiology and present SOX13 as a potential novel cause for CAKUT.

Humans↗

PubMed2026

Identification of mitochondrial energy metabolism-related candidate genes UQCR10 and NDUFA6 in pediatric tetralogy of fallot: an exploratory bioinformatics study.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases in infants and young children. Its molecular basis remains incompletely understood. This study aimed to identify mitochondrial energy metabolism-related candidate genes associated with pediatric TOF using public heart tissue transcriptomic datasets from the GEO database. METHODS: Datasets GSE146218 and GSE217772 were downloaded and merged, followed by batch-effect correction. Differential expression analysis was performed to identify differentially expressed genes (DEGs). Functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), and protein-protein interaction (PPI) network analysis were used to prioritize candidate genes. The Comparative Toxicogenomics Database (CTD) was used as an exploratory literature-based tool to summarize gene-disease associations. RESULTS: A total of 960 DEGs were identified. Functional enrichment analyses showed that these genes were mainly enriched in mitochondrial energy metabolism-related pathways, including oxidative phosphorylation and the mitochondrial respiratory chain. WGCNA and PPI network analyses further prioritized UQCR10 and NDUFA6 as candidate genes, and both genes showed increased expression in TOF heart tissue samples. CTD analysis suggested literature-based associations between these genes and cardiovascular or developmental disease-related terms. CONCLUSION: This exploratory bioinformatics study identified UQCR10 and NDUFA6 as mitochondrial energy metabolism-related candidate genes upregulated in pediatric TOF heart tissue. These findings suggest that mitochondrial respiratory chain-related transcriptional alterations may be involved in TOF-associated myocardial remodeling or stress responses. Further experimental and clinical validation is required to confirm their biological relevance.

Humans↗

PubMed2025

Disease candidate genes prediction using positive labeled and unlabeled instances.

Identifying disease genes and understanding their performance is critical in producing drugs for genetic diseases. Nowadays, laboratory approaches are not only used for disease gene identification but also using computational approaches like machine learning are becoming considerable for this purpose. In machine learning methods, researchers can only use two data types (disease genes and unknown genes) to predict disease candidate genes. Notably, there is no source for the negative data set. The proposed method is a two-step process: The first step is the extraction of reliable negative genes from a set of unlabeled genes by one-class learning and a filter based on distance indicators from known disease genes; this step is performed separately for each disease. The second step is the learning of a binary model using causing genes of each disease as a positive learning set and the reliable negative genes extracted from that disease. Each gene in the unlabeled gene's production and ranking step is assigned a normalized score using two filters and a learned model. Consequently, disease genes are predicted and ranked. The proposed method evaluation of various six diseases and Cancer class indicates better results than other studies.

Humans↗

PubMed2026

Genome-wide association study reveals candidate genes associated with body weight and wool traits in Ordos fine-wool sheep.

BACKGROUND: The Ordos fine-wool sheep is a high-quality fine-wool breed in China, renowned for its excellent wool quality, meat production, and adaptability to the arid and semi-arid regions of Inner Mongolia. Body weight and wool traits are important economic characteristics in sheep breeding. This study aimed to identify genetic loci associated with body weight (BW), wool length (WL), and wool fineness (WF) in Ordos fine-wool sheep. METHODS: A genome-wide association study (GWAS) was conducted in 388 Ordos fine-wool sheep genotyped using the GenoBaits® Ovine 40K SNP panel. Single nucleotide polymorphisms (SNPs) associated with BW, WL, and WF were identified, and candidate genes located near the SNPs reaching the suggestive threshold were subjected to functional annotation and enrichment analysis. RESULTS: A total of 22 SNPs were identified as potentially associated with BW, WL, and WF traits, corresponding to 27 annotated genes. Functional annotation highlighted six potential candidate genes, including LAMA2, ARHGAP18, IGFBP2, IGFBP5, CA10, and AXIN1, which may play important roles in regulating body weight and wool growth in sheep. CONCLUSIONS: The identified genes provide valuable candidate loci for BW, WL, and WF traits in Ordos fine-wool sheep. The results of this study provide preliminary references for further exploration of the genetic mechanisms of wool traits in Ordos fine-wool sheep and the development of molecular breeding markers.

GWAS↗

PubMed2025

Dissecting seed composition QTL from wild soybean: fine-mapping, candidate gene identification, and evaluation of introgression effects on agronomic performance.

Seed composition QTL from wild soybean were confirmed and validated in two genetic backgrounds across multiple environments, candidate genes were identified, and agronomic performance of backcross introgression lines was evaluated. Through selection for soybean yield, breeders have inadvertently reduced seed protein content and increased oil due to phenotypic and genetic correlations between these three traits. Therefore, identifying alleles that increase protein without adversely affecting oil and yield is of interest for breeders and the entire soybean value chain. Previously, a G. max × G. soja population was used to map a protein-associated region to ~ 4.6 Mbp on chromosome (Chr) 14. The G. soja allele significantly increased protein 6.5-7.2 g kg-1, without significantly decreasing oil. Additionally, two oil quantitative trait loci (QTL) were reported on Chrs 8 and 14. In this study, we aimed to confirm the Chr 14 protein QTL, evaluate QTL effects on seed composition and agronomic performance, and further fine-map to identify candidate genes. We validated and fine-mapped the Chr 14 protein QTL to a 0.6 Mbp region in a different genetic background, where the G. soja allele significantly increased protein by 9.3 g kg-1. Further, we confirmed the Chr 14 oil QTL linked to the protein QTL and the Chr 8 oil QTL. Chr 14 protein QTL effects on agronomic traits were evaluated in a backcross population across eight environments. The QTL significantly increased protein content, without significantly impacting oil, maturity, or plant height. While the QTL impacted yield and lodging, its effect and significance varied within environments. The candidate genes identified for these three validated seed composition QTL, along with additional molecular markers developed, offer valuable resources for improving seed composition in soybean breeding programs.

Quantitative Trait Loci↗

PubMed2026

Shared candidate genes associated with variation in egg size in cold-adapted and artificially selected Drosophila melanogaster.

The development of most multicellular organisms begins with oogenesis, the production of the egg. In D. melanogaster, egg size is a highly polygenic trait closely related to fitness. Elements of shifts in egg size have been widely studied and modeled, but the genes underlying this variation are still poorly understood. This study aimed to identify candidate genes associated with processes underlying egg-size variation using D. melanogaster as a model. In selection experiments, we generated large-egg populations from a shared ancestral population using both cold-adaptation and artificial selection, and identified candidate genes for the large-egg phenotype. Using whole-genome DNA sequencing and strict computational filtering, we uncovered single-nucleotide polymorphisms in 10 genes. Characterization of these candidates revealed functions in cytoskeletal dynamics, DNA replication and repair, intracellular signaling, and stem cell maintenance and differentiation. RT-PCR and qPCR were used to validate gene expression differences between cold-adapted lines and the Oregon R control (OrR) in a subset of the candidates. In RT-PCR, stathmin demonstrated a modified expression pattern in all cold-adapted lines relative to OrR controls. In qPCR experiments, Pde1c had significantly higher expression (p < 0.05) in the cold-adapted flies compared to OrR controls for all three fly cages tested. For Ino80, significantly higher expression was observed for one of three cages while one cage showed lower expression. We have assembled a candidate list we hope will be a useful resource for researchers across specialties, from germ cells to cytoskeletal dynamics, to further investigate the genetic and developmental aspects of variation in egg size in D. melanogaster.

Animals↗

PubMed2026

Exploratory identification and cellular functional characterization of ppiabl as a candidate gene associated with growth traits in Paralichthys olivaceus.

The Japanese flounder (Paralichthys olivaceus) is an important mariculture species. However, the genetic mechanisms underlying its growth traits remain poorly understood. To explore the genetic basis of growth variation, whole-genome resequencing was performed in a cultured cohort of 60 individuals, followed by exploratory genome-wide association analysis and candidate-gene prioritization. The results revealed heritability estimates of 0.40 for body weight and 0.24 for body length, with substantial overlap in associated loci between the two traits. Exploratory association and variant-annotation analyses prioritized ppiabl, which carries a nonconservative missense variant, as a candidate gene for further investigation. Tissue expression analysis showed that ppiabl was highly expressed in muscle tissue. This gene encodes a protein belonging to the conserved peptidyl-prolyl cis-trans isomerase family. In Japanese flounder primary muscle cells, ppiabl knockdown was associated with altered expression of growth-related genes and an increased G1-phase fraction, whereas overexpression produced changes in the opposite direction. In line with this, fast-growing individuals were found to have significantly larger muscle fiber areas than slow-growing ones. These findings suggest that ppiabl may be involved in muscle-related cellular processes associated with growth variation in Japanese flounder, although its contribution to whole-animal growth requires further validation. Overall, this exploratory study prioritizes ppiabl as a candidate gene potentially associated with growth-related cellular processes in Japanese flounder, although validation in larger independent populations and in vivo models is required.

Animals↗

PubMed2026

Systematic Approach for Compound Angus Populations Revealing Positional Candidate Genes and Improving Prediction Accuracy in Carcass Traits.

Carcass traits, which reflect growth performance and muscle development, are economically important in beef cattle, yet their genetic determinants remain poorly characterized. Both single-population Genome-wide association studies (GWAS) methods, such as BLINK, and cross-population meta-analysis approaches are widely used to identify genetic variants, yet their comparative performance in genomic prediction for complex traits in structured populations remains underexplored. Few studies have directly compared these methods in genomic prediction. To address this gap, this study aims to (i) identify positional candidate genes associated with carcass traits and (ii) evaluate the context-dependent advantages of Covariate Adjustment (CA) and meta in genomic prediction. In this study, we analyzed carcass weight (CW), live weight (LW), and dressing percentage (DP) in 279 crossbred Angus cattle genotyped with the PHR0105_Bt140K_v1.0 SNP chip. GWAS was performed on the full population using BLINK, and results from three subpopulations were combined via meta-analysis, with significance thresholds for both approaches determined by a shuffle-based method. Candidate genes located within ±10 kb of significant SNPs were associated with different carcass traits, including STRIT1, SEL1L3, NOC4L and ANK1 for DP; SNCA and DNAH5 for CW; and GYPC, GPR158, and GUCY1A1 for LW. Prediction accuracy under MAS and MABLUP showed meta slightly outperformed BLINK in MAS, while BLINK was better with covariate adjustment; after incorporating kinship in MABLUP, meta achieved higher accuracy and population partitioning was negligible. Overall, MABLUP yielded the highest accuracy (0.52-0.79) versus MAS (0.37-0.54) in all traits. These findings provide a methodological basis for selecting appropriate GWAS strategies in structured populations and highlight candidate genes.

GS↗

PubMed2026

Integration of GWAS and WGCNA reveals novel candidate genes for cottonseed oil content in Gossypium hirsutum L.

Genetic improvement of cottonseed oil content represents a crucial strategy for enhancing the comprehensive utilization of cotton. Here, genome-wide association study (GWAS) and weighted gene co-expression network analysis (WGCNA) were integrated to elucidate the genetic control underlying oil content. Phenotypic evaluation of 159 cotton accessions revealed extensive genetic variation, with kernel oil content ranging from 17.81% to 39.50%. Population structure analysis based on 20,213 single nucleotide polymorphisms (SNPs) classified the accessions into two major subpopulations. A total of 18 SNPs exhibited significant associations with oil content, two of which were stably detected across multiple environments using the FarmCPU model. Further haplotype analysis within linkage disequilibrium (LD) blocks confirmed a favorable haplotype on chromosome A05 that was strongly correlated with elevated oil content. Integration of publicly available transcriptome data from 11 ovule developmental stages with WGCNA identified modules significantly linked to oil content. Of the 74 candidate genes within LD intervals, 17 were assigned to WGCNA modules. Functional annotation and enrichment analyses highlighted four putative candidate genes (GH_A05G1503, GH_A05G1506, GH_A05G1531, and GH_A10G2150) involved in oil biosynthesis. These findings deepen our understanding of the genetic mechanisms governing cottonseed oil biosynthesis and lay a foundation for breeding high-oil cotton varieties.

Gossypium↗

PubMed2026

Integrated Genomics and Transcriptomics Reveal Stable Resistance Loci and Candidate Genes for Powdery Mildew in Wheat.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), poses a substantial threat to global wheat production. Enhancing resistance through molecular breeding necessitates a comprehensive understanding of its genetic and molecular underpinnings. This study leveraged a 2-year phenotypic evaluation of 283 diverse wheat accessions combined with genome-wide association studies (GWAS) to pinpoint stable quantitative trait loci for powdery mildew resistance. We identified 52 robust resistance loci across the wheat genome, including seven novel loci consistently detected across four environments. Comparative transcriptome profiling of resistant and susceptible wheat lines revealed 95 differentially expressed genes, predominantly enriched in defense response, signal transduction, and transcription regulation pathways. By integrating the GWAS and transcriptomic data, we precisely identified three compelling candidate genes (TaPIP5K, TaPKG, and TaORR6) on chromosome 2A, which are implicated in cell wall reinforcement, jasmonic acid signaling, and reactive oxygen species scavenging, respectively. Further validation using expression analysis corroborated their pivotal roles in resistance. Our findings provide a rich repository of validated genetic markers, promising candidate genes, and superior resistant germplasms, offering critical resources to accelerate targeted molecular breeding efforts for durable powdery mildew resistance in wheat.

Blumeria graminis f. sp. tritici↗

PubMed2026

Identification of candidate genes for reproductive traits in Chinese Holstein cattle using single-step genome-wide association study.

In dairy farming, reproductive efficiency is vital to both profitability and sustainability. However, years of selective breeding for increased milk yield have adversely affected reproductive potential. This study aimed to pinpoint genomic regions and identify potential candidate genes associated with reproductive traits in Chinese Holstein cattle. In this study, a single-step genome-wide association study (ssGWAS) was conducted using 33,202 phenotypic records from 16,379 animals, 55,244 pedigree records, and genomic data from 1,698 cows. These data were integrated into the ssGWAS analysis, resulting in a total pedigree structure of 21,635 animals. A total of 12 significant markers were identified for calving interval (IC), days open (DO), number of services per conception (NS), and conception rate (CR). Among these significant SNPs, three SNPs were for IC, two SNPs were for DO, three SNPs were for NS, and four SNPs were for CR. Several promising candidate genes located near these SNPs have been identified, including SFXN4, B3GAT2, GRK5, PRDX3, and MTHFD1L, highlighting their potential involvement in fertility-related biological processes. Furthermore, functional enrichment analysis identified significant enrichment of pathways associated with cell adhesion and embryonic development, suggesting a potential mechanistic role for DSG family members (DSG1, DSG2, DSG3, and DSG4) in fertility regulation. Collectively, our findings enhance understanding of the complex genetic basis of reproductive traits in dairy cattle and may offer a valuable set of genomic targets for precision breeding of Chinese Holsteins. Integrating these markers into genomic selection programs may contribute to genetic improvements in reproductive efficiency and support the long-term sustainability of dairy production.

Animals↗

PubMed2026

Identification of Candidate Genes Associated with Growth Traits in Procambarus clarkii Using Whole-Genome Resequencing.

Growth is a critical economic trait in all aquaculture industries. To address issues such as germplasm degradation, a comprehensive understanding of the growth and development mechanisms, along with genetic improvement strategies, for Procambarus clarkii (P. clarkii) is urgently required. In this study, we performed whole-genome resequencing on 89 individuals from five cultured stocks to investigate growth traits (body length) and identified a total of 46,919,297 high-quality single nucleotide polymorphisms (SNPs). Based on these SNPs, we conducted principal component analysis (PCA), phylogenetic analysis, and population genetic structure analysis. Furthermore, we performed selective sweep analysis (using FST, Pi, and XP-CLR) and a genome-wide association study (GWAS) to identify genetic variants associated with growth traits. The results revealed significant genetic differentiation among the five cultured stocks, with the Ma'anshan cultured stock exhibiting the fastest linkage disequilibrium (LD) decay. Additionally, long-term aquaculture in different geographical regions resulted in distinct genetic differences among cultured stocks. Through selective sweep analysis, the intersection of FST, Pi, and XP-CLR across the five populations yielded several growth-related candidate genes: Nephrin, Somatostatin, zinc finger protein 154, and yeti. Subsequent the GWAS identified two candidate genes associated with growth traits: Cullin-associated and neddylation-dissociated protein 1 (CAND1) and Baculoviral IAP repeat-containing protein 8 (BIRC8). These genes are presumed to play pivotal roles in the growth and development of P. clarkii. Overall, our findings provide new insights into the genetic mechanisms underlying growth and development in P. clarkii, and these identified genes serve as promising candidates for further functional studies and genetic improvement of this species.

Polymorphism, Single Nucleotide↗

PubMed2026

Meta-QTL Analysis Reveals Consensus Genomic Regions and Candidate Genes for Resistance to Sudden Death Syndrome in Soybean.

Sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the most economically important diseases limiting soybean production worldwide. Although numerous quantitative trait loci (QTL) associated with SDS resistance have been reported, inconsistencies among mapping populations, marker systems, and experimental conditions have hindered the identification of robust resistance loci for soybean improvement. In this study, a comprehensive meta-analysis was conducted to integrate published QTL and identify stable consensus genomic regions associated with SDS resistance. After a systematic literature survey and data curation, 153 QTL derived from 14 linkage-mapping studies were analyzed using a custom R-based workflow, resulting in the identification of 23 consensus meta-QTL (MQTL) distributed across 17 chromosomes. Several MQTL, particularly those located on chromosomes 6, 8, 18, and 20, were supported by multiple independent studies and represented major genomic hotspots for SDS resistance. Physical localization and functional annotation of these MQTL identified 217 candidate genes, including genes predicted to be involved in plant defense, signal transduction, transcriptional regulation, and secondary metabolism. Gene Ontology enrichment analysis identified response to salicylic acid as the only biological process that remained significant after FDR correction, whereas Kyoto Encyclopedia of Genes and Genomes pathway analysis did not identify significantly enriched pathways. Independent support using five published genome-wide association studies further supported several MQTL, especially those on chromosomes 6, 18, and 20, thereby increasing confidence in these genomic regions. The identified MQTL and prioritized candidate genes provide potential genomic resources for future marker development, improvement applications, and functional validation aimed at improving soybean resistance to SDS.

Fusarium virguliforme↗

PubMed2025

Identification of IDH3G, encoding the gamma subunit of mitochondrial isocitrate dehydrogenase, as a novel candidate gene for X-linked retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP) is a genetically heterogeneous group of retinal degenerative disorders characterized by the loss of rod and cone photoreceptors, leading to visual impairment and blindness. To date, to our knowledge, X-linked RP has been associated with variants in 3 genes (RPGR, RP2, and OFD1), whereas genetic defects at 3 loci (RP6, RP24, and RP34) are yet unidentified. The aim of this study was to identify a novel candidate gene underlying X-linked RP. METHODS: Participants were identified from cohorts of genetically unsolved male individuals affected by RP, who underwent genome sequencing, exome sequencing, or candidate gene screening via direct Sanger sequencing at 3 referral centers. Specifically, 2 probands were identified at the National Reference Centre for Rare Retinal Diseases (Paris, France), 2 at the Massachusetts Eye and Ear Hospital (Boston, MA), and 1 at the National Reference Centre for Inherited Sensory Diseases (Montpellier, France). The pathogenicity of the identified variants was assessed using bioinformatic predictions, protein expression analyses, and mitochondrial function assays. RESULTS: We identified 4 rare single-nucleotide variants in IDH3G (HGNC:5386), located at the RP34 locus on the X chromosome, and a complete gene deletion, in 5 unrelated male individuals affected with nonsyndromic RP. The variants segregated with the phenotype in all available family members. In all cases, the disease severity was intermediate. None had high myopia. IDH3G encodes the γ subunit of mitochondrial isocitrate dehydrogenase (IDH3), an enzyme involved in the citric acid cycle, which is expressed in the inner segments of photoreceptors. Variants in IDH3A and IDH3B, encoding the other subunits of IDH3, have already been associated with nonsyndromic autosomal recessive RP. Bioinformatic predictions and functional assays support a pathogenic role for the variants identified in this study, possibly through partial loss of enzymatic activity and mitochondrial function. CONCLUSION: Our findings suggest that variants in IDH3G are a novel cause of X-linked RP.

Humans↗

PubMed2025

Integrated multi-omics analyses provide new insights into genomic variation landscape and regulatory network candidate genes associated with walnut endocarp.

Persian walnut (Juglans regia) is an economically important nut oil tree; the fruit has a hard endocarp/shell to protect seeds, thus playing a key role in its evolution, and the shell thickness is an important trait for walnut breeding. However, the genomic landscape and the gene regulatory networks associated with walnut shell development remain to be systematically elucidated. Here, we report a high-quality genome assembly of the walnut cultivar 'Xiangling' and construct a graphic structure pan-genome of eight Juglans species to reveal the genetic variations at the genome level. We re-sequence 285 accessions to characterize the genomic variation landscape. Through genome-wide association studies (GWAS), we identified 19 loci associated with more than 268 loci that underwent selection during walnut domestication and improvement. Multi-omics analyses, including transcriptomics, metabolomics, DNA methylation, and spatial transcriptomics across eleven developmental stages, revealed several candidate genes related to secondary cell biosynthesis and lignin accumulation. This integrated multi-omics approach revealed several candidate genes associated with secondary cell biosynthesis and lignin accumulation, such as UGP, MYB308, MYB83, NAC043, NAC073, CCoAOMT1, CCoAOMT7, CHS2, CESA7, LAC7, COBL4, and IRX12. Overexpression of JrUGP and JrMYB308 in Arabidopsis thaliana confirmed their roles in lignin biosynthesis and cell wall thickening. Consequently, our comprehensive multi-omics findings offer novel insights into walnut genetic variation and network regulation of endocarp development and shell thickness, which enable further genome-informed breeding strategies for walnut cultivar improvement.

Juglans↗