Emily A Polk, Robyn E Tanny, Amanda O Shaver, Erik C Andersen, Omer Gokcumen, Denise M Ferkey
{"title":"Natural variation in C. elegans 1-octanol olfactory avoidance behavior.","authors":"Emily A Polk, Robyn E Tanny, Amanda O Shaver, Erik C Andersen, Omer Gokcumen, Denise M Ferkey","doi":"10.1093/g3journal/jkag189","DOIUrl":"10.1093/g3journal/jkag189","url":null,"abstract":"<p><p>The detection of chemical stimuli is a fundamental driver of animal behavior. Odorants and tastants provide essential information about not just food availability and quality, but also about environmental conditions and safety. However, much of what we know about how animals respond to their surroundings comes from the study of a limited number of laboratory-adapted strains of model organisms. In the case of Caenorhabditis elegans, chemosensory research has focused almost exclusively on the N2 strain first isolated in Bristol, England, in 1951, and which has been deemed the wild-type reference for studies of the species since that time. A collection of hundreds of wild C. elegans strains gathered from around the globe and whole-genome sequence data are now available through the Caenorhabditis Natural Diversity Resource. Using these resources, we assessed natural variation in behavioral sensitivity to the aversive odorant 1-octanol. We found that the wild strains either responded similarly to N2 or were less sensitive. No hypersensitive strains were seen among those tested. Using genome-wide association studies we identified a single quantitative trait locus (QTL) on the right arm of chromosome II correlated with diminished behavioral avoidance of 1-octanol and confirmed its role using near-isogenic lines. Building upon our recent report of wild strain taste responses, this study is only the second of this scale to investigate how natural genetic variation shapes C. elegans chemosensory behavior, focusing for the first time on olfaction.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148419933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joana Caetano-Lopes, Valentina Daponte, Katia Urso, Rachel L Roberts, Matthew L Warman, Hicham Drissi, Julia F Charles, Katrin Henke
{"title":"In vivo screen for osteoclast derived osteogenic factors using non-resorptive osteoclasts in zebrafish bone.","authors":"Joana Caetano-Lopes, Valentina Daponte, Katia Urso, Rachel L Roberts, Matthew L Warman, Hicham Drissi, Julia F Charles, Katrin Henke","doi":"10.1093/g3journal/jkag221","DOIUrl":"10.1093/g3journal/jkag221","url":null,"abstract":"<p><p>Bone homeostasis requires the balanced action of bone forming osteoblasts and bone resorbing osteoclasts. This balance is maintained through local as well as systemic factors. Loss of osteoclast resorptive activity leads to development of osteopetrosis with increased bone volume but reduced skeletal integrity. Identification of the factors that regulate such anabolic activity is hampered by the essential function of these genes in development as well as the inaccessibility of large numbers of primary osteoclasts for biochemical analyses. Here, we generated zebrafish with nonresorptive osteoclasts through CRISPR-Cas9 mediated knockout of chloride voltage-gated channel 7 (clcn7). The clcn7 mutants are adult viable, show increased vertebral bone thickness and increased bone formation. Using this in vivo model of persistent, but deficient osteoclasts, we used differential gene expression to identify putative anabolic bone regulators. Transcriptional profiling of clcn7 mutant primary osteoclasts identified differential expression of genes involved in chemotaxis and cytokine signaling. Global transgenic overexpression of a subset of the upregulated, secreted genes showed positive effects of the cytokines csf3b, cxcl19, and the glycosylated peptide progranulin 1 on skeletal parameters, while the cytokine ccl35.1 negatively impacted bone volume. Our findings suggest that the concerted function of these cytokines plays an important role in the regulation of bone homeostasis and that individual cytokines cause distinct changes in vertebral bone form and differentiation.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ye-Ji Kim, Václav Bittner, Kyu-Suk Kang, Christi Sagariya, Milan Lstibůrek
{"title":"OptOrch: a modular optimization toolkit for forest tree seed orchard deployment.","authors":"Ye-Ji Kim, Václav Bittner, Kyu-Suk Kang, Christi Sagariya, Milan Lstibůrek","doi":"10.1093/g3journal/jkag208","DOIUrl":"10.1093/g3journal/jkag208","url":null,"abstract":"<p><p>OptOrch is a transparent and modular optimization toolkit for forest tree seed orchard (SO) deployment. It implements SO-specific optimal contribution models in AMPL (A Mathematical Programing Language), separating biological assumptions, input data, and numerical solvers. Unlike existing optimal-contribution or mate-allocation software, OptOrch exposes the objective function and constraints directly, allowing breeders to modify SO-specific requirements, including status-number thresholds, proportional contribution bounds, graft availability, pairwise coancestry restrictions, female and male gametic contributions, and external pollen flow. When the declared formulation is supported by the selected solver, solutions can be evaluated using solver-reported feasibility status, objective bounds, and optimality gaps. The algebraic framework also allows alternative formulations to be tested when biological constraints create mixed-integer, nonlinear, or nonconvex instances. We demonstrate OptOrch with simulation-based scenarios involving alternative status-number thresholds and pollen contamination. The framework quantifies gain-diversity trade-offs, evaluates external pollen effects, and compares feasible deployment strategies under realistic biological and operational constraints.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian J Stephens, Nathaniel Jacob Turner, Puneet Kaur Mangat, Avinash Shrestha, Md Monjurul Huda, Rosalyn B Angeles-Shim
{"title":"De novo genome assembly of Texas wintergrass [Nassella leucotricha {Trin. & Rupr.} Pohl] supports diagnostic marker development and phylogenetic analysis of species within the family Poaceae.","authors":"Christian J Stephens, Nathaniel Jacob Turner, Puneet Kaur Mangat, Avinash Shrestha, Md Monjurul Huda, Rosalyn B Angeles-Shim","doi":"10.1093/g3journal/jkag225","DOIUrl":"10.1093/g3journal/jkag225","url":null,"abstract":"<p><p>Texas wintergrass is a cool-season perennial bunchgrass native to North America with ecological and agronomic importance as a winter forage species, yet genomic resources for this species remain limited. Here, we present the first de novo genome assembly of Nassella leucotricha generated using PacBio HiFi sequencing. Assembly with hifiasm produced a 959.92-Mb genome with 8× coverage, comprising 2,394 contigs with an N50 of 530.6 kb. Assembly completeness was high, with 99.6% of Benchmarking Universal Single-Copy Orthologs identified, although a substantial proportion were duplicated. Genome size estimates based on flow cytometry and k-mer analysis, together with assembly metrics, indicate a repeat-rich and structurally complex genome. Repeat annotation revealed that 64.42% of the genome consists of repetitive elements, predominantly long terminal repeat retrotransposons, including Ty1/Copia and Gypsy/DIRS1. Gene prediction using the homology-based pipeline GeMoMa identified 54,132 high-confidence genes, of which 53,868 were functionally annotated and 26,346 were assigned to KEGG pathways. Mining for genome-wide simple sequence repeats identified over 38,000 markers, with a validated subset demonstrating use for genetic diversity analysis. Reference-guided alignment and scaffolding using Brachypodium distachyon and Oryza sativa provided comparative frameworks for evaluating conserved sequence relationships between Texas wintergrass and representative grass genomes. Our results establish a genomic resource for Texas wintergrass, supporting future studies in comparative genomics and molecular breeding.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melissa A Castiglione, Matanel Yheskel, Aubrey A Siebels, Simone Sidoli, Julie Secombe
{"title":"A KDM5 variant outside the catalytic Jumonji C domain disrupts demethylase activity and alters the proximity interactome.","authors":"Melissa A Castiglione, Matanel Yheskel, Aubrey A Siebels, Simone Sidoli, Julie Secombe","doi":"10.1093/g3journal/jkag219","DOIUrl":"10.1093/g3journal/jkag219","url":null,"abstract":"<p><p>Transcriptional programs regulated by the KDM5 family of chromatin-modifying proteins are dysregulated in cancer and intellectual disability (ID) disorders. To define the fundamental mechanisms by which KDM5 regulates disease-relevant gene expression, we use missense variants in the X-linked KDM5C gene associated with the ID disorder Claes-Jensen syndrome (also known as KDM5C-NDD). Here, we use Drosophila melanogaster to investigate the effects of KDM5A224T, equivalent to human KDM5CA77T, which affects a conserved residue outside the catalytic histone demethylase JmjC domain and alters both enzymatic and non-enzymatic activities. Quantifying levels of H3K4me3, the demethylase substrate of KDM5, in adult brains revealed that Kdm5A224T induced changes indistinguishable from those observed with a catalytically inactive allele. This effect was not due to reduced promoter recruitment of the variant KDM5A224T protein. Instead, TurboID studies demonstrate that KDM5A224T exhibits reduced proximity with proteins involved in promoter activity and chromatin remodeling. Together, these findings show that KDM5-dependent transcriptional regulation cannot be explained by demethylase activity alone and support altered chromatin regulatory interactions as a key mechanism underlying pathogenic KDM5 variants.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148684030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan Amezquita, Nelson A Ayala, Muriel Desbois, Neal D Mathew, Karla J Opperman, Brock Grill
{"title":"Integrin-Talin axis regulates mechanosensory presynaptic development and behavioral habituation to mechanical stimulation.","authors":"Jonathan Amezquita, Nelson A Ayala, Muriel Desbois, Neal D Mathew, Karla J Opperman, Brock Grill","doi":"10.1093/g3journal/jkag154","DOIUrl":"10.1093/g3journal/jkag154","url":null,"abstract":"<p><p>From invertebrates to mammals, integrin signaling plays important roles in neuron development. β-Integrins are regulated by binding extracellular matrix and through intracellular activation or inside-out signaling via Talin and Kindlin. While Integrins are known to regulate synapse formation and learning, much less is known about effects of Integrins, Talin and Kindlin on presynaptic branch formation and outcomes on behavior. Here, we use Caenorhabditis elegans as an in vivo model to study how the PAT-3/UNC-112/TLN-1 (β-integrin/Kindlin/Talin) signaling axis affects formation of presynaptic branches. Using a CRISPR-based, cell-specific degradation approach, we demonstrate that this Talin axis functions cell-autonomously in mechanosensory neurons to regulate presynaptic branch formation. Transgenic findings indicate TLN-1 inside-out signaling also influences branch formation. Thus, both impairing and activating Talin result in branch defects suggesting that balanced TLN-1 axis signaling is required for branch development. Genetic interaction and developmental time-course studies revealed that the TLN-1 axis functions in parallel with the RPM-1 (MYCBP2) ubiquitin ligase signaling hub to regulate both branch and presynaptic bouton formation. Consistent with the TLN-1 axis affecting presynaptic development in mechanosensory neurons, TLN-1 influences behavioral habituation to repeated low-threshold mechanical stimulation. Collectively, our findings indicate that an Integrin-Talin axis functions cell-autonomously in mechanosensory neurons to regulate presynaptic development and behavioral habituation.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peri A Tobias, Richard J Edwards, Jamie Botting, Giullia di Lorenzo, Vera Inácio, Inês Diniz, Maria do Céu Silva, Leonor Guerra-Guimarães, Vitor Várzea, Robert F Park, Dora Batista
{"title":"A pseudo-phased genome assembly for Hemileia vastatrix reveals an isolate-specific chromosomal haploid trisomy.","authors":"Peri A Tobias, Richard J Edwards, Jamie Botting, Giullia di Lorenzo, Vera Inácio, Inês Diniz, Maria do Céu Silva, Leonor Guerra-Guimarães, Vitor Várzea, Robert F Park, Dora Batista","doi":"10.1093/g3journal/jkag214","DOIUrl":"10.1093/g3journal/jkag214","url":null,"abstract":"<p><p>Recurrent epidemics of coffee leaf rust, caused by the fungal pathogen Hemileia vastatrix, have constrained production of Arabica coffee for over 150 years. Here, we present a pseudo-phased, chromosome-level genome resource for H. vastatrix, isolate Hv178a, to guide research into disease management. The Hv178a genome assembly is 665 and 638 Mbp for haplotype A and B, respectively, localized to 18 chromosomes. We determined that the genomes are highly repetitive at ∼94%, with a guanine-cytosine (GC) content of 33.5%. We present the full annotation of 13,760 and 17,998 protein-coding genes, and we predicted 452 and 496 effectors in haplotype A and B, respectively. Depth-based comparisons with 11 additional H. vastatrix isolates revealed increased chromosome 17 (chr17) copy number in Hv178a. qPCR validation supports a chr17 trisomy in Hv178a absent from the ancestral lineage and potentially explaining the observed change in virulence.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carina de Oliveira Anoni, Kaio Olímpio das Graças Dias, Martin Boer, Marcos Malosetti, Lauro José Moreira Guimarães, Paulo Evaristo de Oliveira Guimarães, Marcos José Andrade Viana, Maurício de Alvarenga Mudadu, Edson Alves Bastos, Milton José Cardoso, Roberto Willians Noda, Juliana E de C T Yassitepe, Jurandir Vieira de Magalhaes, Antônio Augusto Franco Garcia, Fred van Eeuwijk, Claudia Teixeira Guimarães, Maria Marta Pastina
{"title":"Multienvironment multilocus association mapping reveals genomic regions for drought-related traits in tropical maize.","authors":"Carina de Oliveira Anoni, Kaio Olímpio das Graças Dias, Martin Boer, Marcos Malosetti, Lauro José Moreira Guimarães, Paulo Evaristo de Oliveira Guimarães, Marcos José Andrade Viana, Maurício de Alvarenga Mudadu, Edson Alves Bastos, Milton José Cardoso, Roberto Willians Noda, Juliana E de C T Yassitepe, Jurandir Vieira de Magalhaes, Antônio Augusto Franco Garcia, Fred van Eeuwijk, Claudia Teixeira Guimarães, Maria Marta Pastina","doi":"10.1093/g3journal/jkag220","DOIUrl":"10.1093/g3journal/jkag220","url":null,"abstract":"<p><p>Maize grain yield is frequently constrained by water scarcity, particularly in tropical regions characterized by irregular rainfall patterns. Dissecting the genetic basis of drought-related traits remains challenging because their expression is strongly influenced by environmental conditions. In this study, we applied a multienvironment multilocus genome-wide association study to identify genomic regions associated with drought-related traits in tropical maize. The association panel comprised 190 inbred lines from the Embrapa breeding program, which were genotyped-by-sequencing with 500,108 single nucleotide polymorphisms (SNPs) and crossed with 2 tester lines. Phenotypic data corresponded to the performance of the testcross hybrids, divided into Dent and Flint heterotic groups, evaluated across 2 yr at 2 locations in Brazil under well-watered and water-stressed conditions. Traits analyzed included grain yield, anthesis-silking interval, female and male flowering time, and plant and ear height. Drought stress reduced grain yield by approximately 50% and increased the anthesis-silking interval by about 2 d. A total of 179 significant SNP-trait associations were detected, of which 166 showed significant SNP-by-environment interaction effects, while 13 displayed stable effects across environments. Several associations were detected specifically under water-stressed conditions, highlighting genomic regions potentially involved in drought adaptation. Functional annotation revealed candidate genes previously implicated in abiotic stress responses, including ZmTIP1, which encodes an S-acyltransferase regulating root hair development and drought tolerance. Among the novel candidate genes, GRMZM2G159125, encoding a phospholipase D, emerged as a particularly promising candidate due to its strong association with grain yield and its role in membrane lipid signaling pathways related to stress responses. Although a few associations overlapped genomic regions previously reported for drought tolerance in maize, most loci represent potentially novel genetic factors that may contribute to improving drought resilience in tropical maize breeding programs.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
William Dion, Emily Washeleski, Tessa E Steenwinkel, Emily Taylor, Prajakta P Kokate, Aidan VanDrie, Thomas Werner, Paul D Goetsch
{"title":"Draft hybrid assembly and annotation of the Drosophila palustris and Drosophila subpalustris genomes.","authors":"William Dion, Emily Washeleski, Tessa E Steenwinkel, Emily Taylor, Prajakta P Kokate, Aidan VanDrie, Thomas Werner, Paul D Goetsch","doi":"10.1093/g3journal/jkag226","DOIUrl":"10.1093/g3journal/jkag226","url":null,"abstract":"<p><p>Species within the quinaria group of the genus Drosophila are models for ecological genetic studies on topics that include morphological diversity, color pattern development, and feeding behavior. Drosophila palustris and Drosophila subpalustris are closely related members within the quinaria species group that differ primarily in subtle morphological and behavioral traits. To support future evolutionary genomic studies in drosophilids, we completed new draft hybrid assemblies and annotations of the D. palustris and D. subpalustris genomes. We obtained a fragmented assembly for D. palustris (N50 = 874 Kb) and a near chromosome-scale D. subpalustris assembly (N50 = 27.5 Mbp). Assembly contiguity, repeat content, and gene annotation compared well to other published quinaria group genomes. To demonstrate the utility of our hybrid assemblies, we performed whole-genome synteny and phylogenomic comparisons within the quinaria clade. When compared to the chromosome-level Drosophila innubila assembly, the median size of syntenic blocks among quinaria group genomes was approximately 1 Mbp, although this estimate was influenced by assembly contiguity. Phylogenomic analyses estimated that the 2 major branches of the quinaria group diverged ∼17.9 MYA, with D. palustris and D. subpalustris diverging ∼1 to 2 MYA. We expect that our D. palustris and D. subpalustris assemblies will provide important additions to studies of genome evolution within Drosophilidae.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paul P R Iyyanar, Andrew Vontell, Ammar Husami, Ethan Sperry, K Nicole Weaver, Rolf W Stottmann
{"title":"Involvement of tumor suppressor candidate 3 in mouse survival, craniofacial, and cortical development.","authors":"Paul P R Iyyanar, Andrew Vontell, Ammar Husami, Ethan Sperry, K Nicole Weaver, Rolf W Stottmann","doi":"10.1093/g3journal/jkag224","DOIUrl":"10.1093/g3journal/jkag224","url":null,"abstract":"<p><p>Tumor suppressor candidate 3 is an integral component of the oligosaccharyltransferase complex and is required for the N-glycosylation of proteins. While tumor suppressor candidate 3 has been implicated in cancer and autosomal recessive non-syndromic intellectual disability, some patients also exhibit distinct facial features. However, the role of Tusc3 in craniofacial development is unknown. Here, we report a patient presenting with cleft lip and palate who was found to carry a homozygous variant in the TUSC3 promoter region in addition to a maternally inherited chromosomal duplication. In order to evaluate a potential role for TUSC3 in craniofacial development, we analyzed Tusc3 deletion mouse mutants from the International Mouse Phenotyping Consortium (IMPC). Initial IMPC phenotyping data suggested that a subset of Tusc3 deletion mice could develop cleft palate, micrognathia, and aglossia. We further identified that Tusc3 is expressed in the craniofacial and brain regions during embryonic development. Upon characterizing the Tusc3 deletion line, we observed that most homozygous mutants exhibit preweaning lethality. While craniofacial defects occur at a very low frequency in the deletion mutants, we identified a modest reduction in cortical area. Furthermore, RNA-seq analysis surprisingly revealed that no other genes in the developing brain or face were significantly affected upon loss of Tusc3. These findings suggest that Tusc3 can contribute to congenital malformations in both craniofacial and cortical development.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}