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genetics

genetics: explore 9 source-linked works published from 2026 to 2026, with original documents and citations.

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Sources: biorxiv. Collection updated 2026-09-17. Counts describe this index, not the complete source archives.

bioRxiv2026

The histone demethylase Kdm5 and the ARGONAUTE proteins Piwi and Aubergine regulate female abdominal pigmentation in Drosophila melanogaster

Insect pigmentation is an ecologically critical trait influencing many physiological processes. In Drosophila melanogaster, abdominal pigmentation is sexually dimorphic: males have fully pigmented posterior segments, while females exhibit a posterior melanin stripe. Pigmentation relies on the expression of pigmentation genes that encode enzymes involved in pigment synthesis. These genes are tightly regulated during pupal and young adult stages. To expand the gene regulatory network of pigmentation genes, we conducted an RNAi screen using the yellow-Gal4 driver, expressed during the pupal stage in abdominal epidermis. One of the candidates from this screen, Kdm5, encodes a histone demethylase erasing the H3K4me3 histone mark catalyzed by the histone methyl-transferase Trithorax (Trx). We show that Kdm5 down-regulation reduces abdominal pigmentation, mimicking trx down-regulation. Kdm5 activates melanin production through regulation of the pigmentation gene tan. Transcriptomic analyses reveal that Kdm5 and Trx share many targets in pupal abdominal epidermis, including piRNA pathway components such as piwi and aubergine. These piRNA components, originally associated with transposon silencing in the germline, also function in some somatic tissues such as the nervous system, the fat body or the gut. We demonstrate that Piwi and Aubergine participate in female abdominal pigmentation establishment, without evident piRNA production. We also show that Kdm5 and Piwi act not only in pupal abdominal epidermis but also in pupal fat body. This study therefore expands the regulatory network of pigmentation genes. It identifies a new somatic function for Kdm5 and Piwi and reveals a role for pupal fat body in female abdominal pigmentation regulation.

genetics↗

bioRxiv2026

Genetic diversity within and between polyploid sugarcane (Saccharum spp.) families obtained via caryopsis using microsatellite markers and multicategory model

Genetic diversity analyses are essential for sugarcane (Saccharum spp.) breeding programs. Crossbreeding, based on genetic distances between parental plants, is a tool used to increase genetic variability and enhance plant selection; however, quantifying variation in highly polyploid species remains a challenge. The present study aimed to evaluate the diversity within and between 12 families of sugarcane derived from caryopses, analyzing 120 individual seedlings arranged in an augmented block design. Genotyping was performed using primers for 16 microsatellite loci, five simple sequence repeat (SSR) loci, and 11 expressed sequence tag-SSR (EST-SSR) loci. To accurately account for polyploidy, similarity calculations were performed using Bruvos distances among individuals and RST distances among the families. Analysis of molecular variance (AMOVA) indicated that most of the genetic variability was within families (72%), with only 28% found between them. This high level of intra-family variation demonstrates that a significant reservoir of genetic diversity remains available within the crosses. The highest genetic similarity was observed between the families RB986952 x RB986960 and RB036122 x RB03611, whereas the lowest genetic similarity was observed between the families RB97319 x RB966928 and RB106802 x RB855036. Although the evaluated families shared high genetic similarity, the pronounced genetic variation within them demonstrates a robust recombination potential, indicating that the genetic basis of sugarcane can be better explored using the high variability that already exists in the selection of desirable morpho-agronomic characteristics within the families. Furthermore, this study highlights the importance of using appropriate distances for diversity studies with codominant markers, such as microsatellites, in polyploid species.

genetics↗

bioRxiv2026

Optimizing DNA extraction from environmentally degraded bone samples for molecular identification of cetacean species

Molecular identification of cetacean bone remains can be limited by DNA degradation and the presence of PCR inhibitors. Here, we present an optimized DNA extraction protocol based on a total demineralization method for environmentally exposed cetacean bones. The protocol uses 100 mg of bone powder, 24 h digestion with EDTA, N-lauroylsarcosine, and proteinase K, followed by a modified silica-column purification. Nine environmentally degraded bone samples representing eight individuals were processed. DNA concentrations ranged from 7.3 to 57.1 ng/uL (mean SD = 25.91- 13.91 ng/uL). The mitochondrial cytochrome b gene was successfully amplified from all samples using conventional PCR, and five samples (55.6%) yielded sequences suitable for downstream analysis. BLASTn identified Balaenoptera physalus as the closest database match for all recovered sequences, and phylogenetic analysis further supported their association with B. physalus reference sequences. These results demonstrate that the proposed protocol provides a practical approach for recovering amplifiable and molecularly informative mitochondrial DNA from environmentally degraded cetacean bone material, facilitating molecular identification from challenging skeletal remains.

genetics↗

bioRxiv2026

A patient-derived LMX1B variant causes tissue-specific manifestations of nail-patella syndrome in mice

Nail-patella syndrome (NPS) is a multisystem disorder caused by pathogenic variants in LMX1B and is characterized by dysplasia of the nails and patellae as well as extraskeletal complications such as progressive nephropathy and glaucoma. We generated a CRISPR/Cas9 knock-in mouse carrying the R252Q substitution, corresponding to a human LMX1B variant associated with renal-predominant disease. Phenotypic analysis revealed that homozygous mice were viable, but they displayed marked growth retardation and severe bilateral ocular opacity. Interestingly, while this model exhibited clear skeletal and ocular defects, the renal phenotype was relatively mild, although increased urinary albumin excretion, focal glomerular basement membrane abnormalities, and subtle changes in renal gene expression were detected. Beyond the classical NPS hallmarks, mutant mice also displayed midbrain morphological abnormalities, suggesting broader developmental consequences of this LMX1B variant. This patient-derived variant model not only recapitulates the pleiotropic features of NPS but also demonstrates organ-specific susceptibility to the R252Q substitution, providing a foundation for elucidating the complex molecular mechanisms underlying multisystem disease.

genetics↗

bioRxiv2026

A mutation-agnostic and allele-specific ASO strategy demonstrates potent functional rescue and retinal preservation in RHO-linked retinitis pigmentosa

Autosomal dominant retinitis pigmentosa (adRP) caused by RHO mutations is a leading form of inherited retinal degeneration. Extensive allelic heterogeneity of RHO pathogenic variants limits the translational applicability of mutation-specific gene therapies. To address this, we developed SNARE (SNP-guided Silencing of Aberrant RHO Expression), a mutation-independent, allele-specific antisense oligonucleotide (ASO) strategy. SNARE selectively suppresses mutant RHO transcripts by targeting the common, benign c.-26A/G single-nucleotide polymorphism (SNP) as an allelic discriminator. Candidate gapmer ASOs were screened in engineered reporter lines and validated in patient-derived retinal organoids, identifying RHOligo-A as the lead c.-26A-targeting candidate. In vitro, RHOligo-A achieved robust, preferential knockdown of the target allele, improving RHO localization in retinal organoids, and demonstrated a favorable safety profile with minimal transcriptomic off-target effects and no detectable immunostimulatory activity. Subsequent validation in a novel, humanized RHOP347L/WT mouse model, achieved sustained c.-26A-linked allele-selective suppression, retinal structure preservation, and significantly restored visual function, upon a single intravitreal administration. These findings establish RHOligo-A and SNARE as a scalable, mutation-independent therapeutic platform with strong translational potential and substantial clinical reach for RHO-associated adRP.

genetics↗

bioRxiv2026

Paternal regulation of H3K4 methylation supports tumor suppressor networks in mammals intergenerationally

Paternally-inherited epigenetic information can influence phenotype in offspring (1). Here, we identify a critical mechanistic contribution of KDM6A (UTX), an X-linked histone modifier and tumor suppressor, in regulating transmissible epigenetic information in mammalian sperm. Paternal loss of KDM6A increases cancer risk in genetically wild type offspring, but how Kdm6a knockout sperm transmit this effect at the molecular level is unknown (2). We find that KDM6A functions in spermatogenesis to promote methylation of histone H3 lysine 4 (H3K4) via selective interaction with the COMPASS complex methyltransferase KMT2C (MLL3). KMT2C and KDM6A are coordinately recruited to promoters of active genes in spermatogenic cells, contrasting with recruitment to intergenic enhancers in other cell types (3, 4). Loss of KDM6A disrupts H3K4 methylation at promoters of tumor suppressor genes in spermatogonia, and some of these defects persist in epididymal sperm and correspond to impaired expression in preimplantation embryos. These genes are also misregulated in normal and malignant hematopoietic tissue of genetically wild type offspring, indicating that impaired H3K4 methylation in KDM6A-deficient male germ cells may preferentially alter regulation of tumor suppressor gene networks in development across generations.

genetics↗

bioRxiv2026

TigerAI: An AI-powered genetic evidence platform to support clinical development

Genetic evidence is a major determinant of clinical success in drug development, yet its aggregation has long relied on laborious human curation. Large language models (LLMs) have the potential to rapidly synthesize knowledge across biomedical resources, providing a route to scalable AI-driven genetic evidence generation. Here we develop a novel domain-grounded instruction framework to systematically evaluate GPT-5 for producing genetic evidence relevant to clinical trial success. Using 13,022 target-indication pairs from a comprehensive drug development database, we benchmark LLM-derived evidence against a recent exhaustive human expert-curated study. We find that GPT-5 yields genetic evidence that is at least as informative as expert curation for inferring clinical success, while substantially expanding coverage relative to traditional curation resources. Building on these results, we introduce TigerAI (https://tigerai.bio/), a dual-purpose platform for AI-powered genetic evidence that (i) benchmarks emerging state-of-the-art LLMs and (ii) provides an accessible service for querying reliable AI-generated genetic evidence. These contributions outline a practical, domain-grounded pathway for integrating AI-powered genetic evidence into drug development pipelines and for realizing the potential of LLMs to inform clinical success.

genetics↗

bioRxiv2026

Parallel evolution under constraint shapes echinocandin resistance in Candida auris

Drug resistance emerges repeatedly in outbreaks of Candida fungal pathogens, but little is known about its origins or persistence. Here, we investigated the evolutionary processes shaping echinocandin resistance in Candida auris, a globally emerging and predominantly clonal fungal pathogen. Genome-wide association across over 600 isolates identified mutations in the {beta}-1,3-glucan synthase gene FKS1 as the most significant driver of resistance to an echinocandin drug. Ancestral reconstruction of this population traced shared resistance mutations among small groups typically consisting of 2-3 closely related isolates, but clusters could include up to 16 isolates. Nearly all resistant clusters consisted of isolates collected in the same year and region, consistent with local transmission. To further examine population-level selection, we measured adaptive signatures in FKS1 and the highly diverged paralog FKS2 across 22,000 genomes. This revealed excess nonsynonymous polymorphisms in FKS1, primarily due to independent, recurrent mutations at resistance hotspots, consistent with parallel evolution and incomplete fixation of adaptive alleles. In FKS2, there is no evidence of hotspots and little support for diversifying selection. Together, these results indicate that resistance mutations emerge under strong genetic constraint, with adaptation restricted to only one FKS homolog and predominantly at mutational hotspots.

genetics↗

bioRxiv2026

X-inactivation escapee domains are CTCF-cohesin independent chromatin compartments

X-chromosome inactivation involves chromosome-wide gene silencing accompanied by extensive chromatin changes, as well the loss of topologically associating domains. Yet discrete regions of the inactive X chromosome retain activity within localised 3D domains, which contain active genes that variably escape from X inactivation. The transcription factor and architectural protein CTCF has been proposed to be implicated in escape by insulating escape domains or sustaining their topology via cohesin-mediated loop extrusion. Here, we test the role of CTCF and cohesin in escape using acute degron-mediated depletion of CTCF and RAD21 in neural progenitor cells with established escape profiles. Although CTCF occupancy correlates with escape status on the inactive X chromosome, its removal - together with loss of loop extrusion - does not disrupt escapee gene expression, or domain organization, nor does it result in spreading of silencing or activation of genes in cis. Rather, we show that facultative escape regions are self-sustaining compartments of active chromatin enriched in H3K27 acetylation and depleted in H3K27 methylation, with the magnitude of compartment strength scaling up with the degree of transcriptional activity on the inactive X chromosome. These active escapee compartments are propagated independently of CTCF and RAD21-dependent 3D architecture. Our findings identify chromatin compartmentalization as the primary feature of facultative escapee domains.

genetics↗

Compare source metadata on this page

Work	Published	Source identifier	Source
The histone demethylase Kdm5 and the ARGONAUTE proteins Piwi and Aubergine regulate female abdominal pigmentation in Drosophila melanogaster	2026-09-03	10.64898/2026.08.27.747613v1	biorxiv
Genetic diversity within and between polyploid sugarcane (Saccharum spp.) families obtained via caryopsis using microsatellite markers and multicategory model	2026-09-03	10.64898/2026.08.28.747747v1	biorxiv
Optimizing DNA extraction from environmentally degraded bone samples for molecular identification of cetacean species	2026-09-03	10.64898/2026.08.31.748265v1	biorxiv
A patient-derived LMX1B variant causes tissue-specific manifestations of nail-patella syndrome in mice	2026-09-02	10.64898/2026.08.28.747744v1	biorxiv
A mutation-agnostic and allele-specific ASO strategy demonstrates potent functional rescue and retinal preservation in RHO-linked retinitis pigmentosa	2026-09-01	10.64898/2026.08.25.747013v1	biorxiv
Paternal regulation of H3K4 methylation supports tumor suppressor networks in mammals intergenerationally	2026-09-01	10.64898/2026.08.28.747954v1	biorxiv
TigerAI: An AI-powered genetic evidence platform to support clinical development	2026-09-01	10.64898/2026.08.29.748046v1	biorxiv
Parallel evolution under constraint shapes echinocandin resistance in Candida auris	2026-09-01	10.64898/2026.08.30.748140v1	biorxiv
X-inactivation escapee domains are CTCF-cohesin independent chromatin compartments	2026-09-01	10.64898/2026.08.31.748372v1	biorxiv

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