Search Results (9)

Single-cell RNA sequencing (scRNA-seq) enables expression quantitative trait locus (eQTL) analysis at cellular resolution, offering new opportunities to uncover regulatory variants with cell-type-specific effects. However, existing tools are often limited in functionality, input compatibility, or scalability for sparse single-cell data. To address these challenges, we developed scQTLtools, a comprehensive R/Bioconductor package that facilitates end-to-end single-cell eQTL analysis, from preprocessing to visualization. The toolkit supports flexible input formats, including Seurat and SingleCellExperiment objects, handles both binary and three-class genotype encodings, and provides dedicated functions for gene expression normalization, SNP and gene filtering, eQTL mapping, and versatile result visualization. To accommodate diverse data characteristics, scQTLtools implements three statistical models—linear regression, Poisson regression, and zero-inflated negative binomial regression. We applied scQTLtools to scRNA-seq data from human acute myeloid leukemia and identified eQTLs with regulatory effects that varied across cell types. Visualization of SNP–gene pairs revealed both positive and negative associations between genotype and gene expression. These results demonstrate the ability of scQTLtools to uncover cell-type-specific regulatory variation that is often missed by bulk eQTL analyses. Currently, scQTLtools supports cis-eQTL mapping; future development will extend to include trans-eQTL detection. Overall, scQTLtools offers a robust, flexible, and user-friendly framework for dissecting genotype–expression relationships in heterogeneous cellular populations. Full article

The e4 allele of the apolipoprotein E gene is the strongest genetic risk factor for sporadic Alzheimer’s disease. Nevertheless, how APOE is regulated is still elusive. In a trans-eQTL analysis, we found a genome-wide significant association between transmembrane protein 106B (TMEM106B) genetic variants and cortical APOE mRNA levels in human brains. The goal of this study is to determine whether TMEM106B is mis-regulated in Alzheimer’s disease or in other neurodegenerative conditions. Available genomic, transcriptomic and proteomic data from human brains were downloaded from the Mayo Clinic Brain Bank and the Religious Orders Study and Memory and Aging Project. An in-house mouse model of the hippocampal deafferentation/reinnervation was achieved via a stereotaxic lesioning surgery to the entorhinal cortex, and mRNA levels were measured using RNAseq technology. In human temporal cortices, the mean TMEM106B expression was significantly higher in Alzheimer’s disease compared to cognitively unimpaired individuals. In the mouse model, hippocampal Tmem106b reached maximum levels during the early phase of reinnervation. These results suggest an active response to tissue damage that is consistent with compensatory synaptic and terminal remodeling. Full article

Despite collective efforts to understand the complex regulation of reproductive traits, no causative genes and/or mutations have been reported yet. By integrating genomics and transcriptomics data, potential regulatory mechanisms may be unveiled, providing opportunities to dissect the genetic factors governing fertility. Herein, we identified regulatory variants from RNA-Seq data associated with gene expression regulation in the uterine luminal epithelial cells of beef cows. We identified 4676 cis and 7682 trans eQTLs (expression quantitative trait loci) affecting the expression of 1120 and 2503 genes, respectively (FDR < 0.05). These variants affected the expression of transcription factor coding genes (71 cis and 193 trans eQTLs) and genes previously reported as differentially expressed between pregnant and nonpregnant cows. Functional over-representation analysis highlighted pathways related to metabolism, immune response, and hormone signaling (estrogen and GnRH) affected by eQTL-regulated genes (p-value ≤ 0.01). Furthermore, eQTLs were enriched in QTL regions for 13 reproduction-related traits from the CattleQTLdb (FDR ≤ 0.05). Our study provides novel insights into the genetic basis of reproductive processes in cattle. The underlying causal mechanisms modulating the expression of uterine genes warrant further investigation. Full article

Shrub willows are widely planted for landscaping, soil remediation, and biomass production, due to their rapid growth rates. Identification of regulatory genes in wood formation would provide clues for genetic engineering of willows for improved growth traits on marginal lands. Here, we conducted an expression quantitative trait locus (eQTL) analysis, using a full sibling F₁ population of Salix suchowensis, to explore the genetic mechanisms underlying wood formation. Based on variants identified from simplified genome sequencing and gene expression data from RNA sequencing, 16,487 eQTL blocks controlling 5505 genes were identified, including 2148 cis-eQTLs and 16,480 trans-eQTLs. eQTL hotspots were identified, based on eQTL frequency in genomic windows, revealing one hotspot controlling genes involved in wood formation regulation. Regulatory networks were further constructed, resulting in the identification of key regulatory genes, including three transcription factors (JAZ1, HAT22, MYB36) and CLV1, BAM1, CYCB2;4, CDKB2;1, associated with the proliferation and differentiation activity of cambium cells. The enrichment of genes in plant hormone pathways indicates their critical roles in the regulation of wood formation. Our analyses provide a significant groundwork for a comprehensive understanding of the regulatory network of wood formation in S. suchowensis. Full article

In response to Pi deprivation, phosphate 1 (PHO1) is a significant regulator at trans-eQTL hotspots in Brassica rapa. Brassica rapa short-read sequencing data analysis revealed four PHO1 paralog genes, PHO1_A, PHO1_B, PHO1_C, and PHO1_D, placed in tandem with very high sequence similarity. However, based on short-read genomic sequence data, only three transcripts are accessible. Five bacterial artificial chromosomes (BACs) can be sequenced using a long-read sequencer, which improves de novo assembly and identifies structural variants. The PHO1 gene’s quadruplicating tandem positions in the genomic sequence were confirmed by an analysis of long-read data. Transcript analysis identified only three groups of PHO1 paralogs (ortholog AT1G14040 in Arabidopsis), i.e., PHO1_A, PHO1_B, and PHO1_D, expressed in B. rapa leaf tissues under Pi deficiency. PHO1_A, with transcript ID XM_009150437.2, has five different splice variants found. These splice variants’ truncated proteins demonstrated PHO1_A’s function in P control as opposed to protein encoding. Full article

Single nucleotide polymorphisms (SNPs) impacting the alternative splicing (AS) process (sQTLs) or isoform expression (iso-eQTL) are implicated as important cancer regulatory elements. To find the sQTL and iso-eQTL, we retrieved prostate cancer (PrCa) tissue RNA-seq and genotype data originating from 385 PrCa European patients from The Cancer Genome Atlas. We conducted RNA-seq analysis with isoform-based and splice event-based approaches. The MatrixEQTL was used to identify PrCa-associated sQTLs and iso-eQTLs. The overlap between sQTL and iso-eQTL with GWAS loci and those that are differentially expressed between cancer and normal tissue were identified. The cis-acting associations (FDR < 0.05) for PrCa-risk SNPs identified 42, 123, and 90 PrCa-associated cassette exons, intron retention, and mRNA isoforms belonging to 25, 95, and 83 genes, respectively; while assessment of trans-acting association (FDR < 0.05) yielded 59, 65, and 196 PrCa-associated cassette exons, intron retention and mRNA isoforms belonging to 35, 55, and 181 genes, respectively. The results suggest that functional PrCa-associated SNPs can play a role in PrCa genesis by making an important contribution to the dysregulation of AS and, consequently, impacting the expression of the mRNA isoforms. Full article

We investigated the extent of the heritability underestimation for molecules from an infinitesimal model in mixed model analysis. To this end, we estimated the heritability of transcription, ribosome occupancy, and translation in lymphoblastoid cell lines from Yoruba individuals. Upon considering all genome-wide nucleotide variants, a considerable underestimation in heritability was observed for mRNA transcription (−0.52), ribosome occupancy (−0.48), and protein abundance (−0.47). We employed a mixed model with an optimal number of nucleotide variants, which maximized heritability, and identified two novel expression quantitative trait loci (eQTLs; p < 1.0 × 10⁻⁵): rs11016815 on chromosome 10 that influences the transcription of SCP2, a trans-eGene on chromosome 1—whose expression increases in response to MGMT downregulation-induced apoptosis, the cis-eGene of rs11016815—and rs1041872 on chromosome 11 that influences the ribosome occupancy of CCDC25 on chromosome 8 and whose cis-eGene encodes ZNF215, a transcription factor that potentially regulates the translation speed of CCDC25. Our results suggest that an optimal number of nucleotide variants should be used in a mixed model analysis to accurately estimate heritability and identify eQTLs. Moreover, a heterogeneous covariance structure based on gene identity and the molecular layers of the gene expression process should be constructed to better explain polygenic effects and reduce errors in identifying eQTLs. Full article

The last century has witnessed rapid domestication of the narrow-leafed lupin (Lupinus angustifolius L.) as a grain legume crop, exploiting discovered alleles conferring low-alkaloid content (iucundus), vernalization independence (Ku and Julius), and reduced pod shattering (lentus and tardus). In this study, a L. angustifolius mapping population was subjected to massive analysis of cDNA ends (MACE). The MACE yielded 4185 single nucleotide polymorphism (SNP) markers for linkage map improvement and 30,595 transcriptomic profiles for expression quantitative trait loci (eQTL) mapping. The eQTL highlighted a high number of cis- and trans-regulated alkaloid biosynthesis genes with gene expression orchestrated by a regulatory agent localized at iucundus locus, supporting the concept that ETHYLENE RESPONSIVE TRANSCRIPTION FACTOR RAP2-7 may control low-alkaloid phenotype. The analysis of Ku shed light on the vernalization response via FLOWERING LOCUS T and FD regulon in L. angustifolius, providing transcriptomic evidence for the contribution of several genes acting in C-repeat binding factor (CBF) cold responsiveness and in UDP-glycosyltransferases pathways. Research on lentus selected a DUF1218 domain protein as a candidate gene controlling the orientation of the sclerified endocarp and a homolog of DETOXIFICATION14 for purplish hue of young pods. An ABCG transporter was identified as a hypothetical contributor to sclerenchyma fortification underlying tardus phenotype. Full article

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder that displays a great clinical variability. Previous work in our laboratory showed that fibrillin-1 (FBN1) messenger RNA (mRNA) expression is a surrogate endpoint for MFS severity. Therefore, an expression quantitative trait loci (eQTL) analysis was performed to identify trans-acting regulators of FBN1 expression, and a significant signal reached genome-wide significant threshold on chromosome 11. This signal delineated a region comprising one expressed gene, SLN (encoding sarcolipin), and a single pseudogene, SNX7-ps1 (CTD-2651C21.3). We first investigated the region and then looked for association between the genes in the region and FBN1 expression. For the first time, we showed that the SLN gene is weakly expressed in skin fibroblasts. There is no direct correlation between SLN and FBN1 gene expression. We showed that calcium influx modulates FBN1 gene expression. Finally, SLN gene expression is highly correlated to that of the neighboring SNX7-ps1. We were able to confirm the impact of calcium influx on FBN1 gene expression but we could not conclude regarding the role of sarcolipin and/or the eQTL locus in this regulation. Full article