Biology subjects

Dubuc, A.

Publications and source records attributed to Dubuc, A..

4 recordsLinked to original sources

bioRxiv2025

Cross-species consensus atlas of the primate basal ganglia

The basal ganglia (BG) are conserved brain regions essential for motor control, learning, emotion, and cognition, and are implicated in neurological and psychiatric disease. Yet a unified cross-species taxonomy of BG cell types is lacking, limiting translation of BG circuit mechanisms, interpretation of human genetic risk, and development of cell type-targeted tools. We present a multiomic consensus atlas of 1.8 million nuclei from human, macaque, and marmoset spanning eight BG structures. Integrating cross-species gene expression, open chromatin, and spatial profiling enables definition of conserved and divergent cell types. Alignment to existing mouse and human atlases identifies 61 homologous cell types conserved over 80 million years. We identify a STRd D2 StrioMat Hybrid medium spiny neuron (MSN) type with molecular, electrophysiological, and morphological features that clarify hybrid MSN identities. Comparative cis-regulatory analysis reveals conserved sequence grammars that encode cell identity and inform viral targeting strategies, providing a foundational resource for BG evolution, function, and disease.

neuroscience↗

bioRxiv2025

Genetic and Cortical Cell-Type Liability Architecture of Autism

Autism Spectrum Disorders (ASD) can result from rare genetic variants interfering with brain development. Whether their effects converge on specific cortical cell types remains unresolved. Previous studies have focused on a narrow set of high-confidence ASD (hcASD) genes, which were enriched in neuronal cell types during prenatal development. By contrast, studies of postnatal cerebral cortex have repeatedly associated ASD with transcriptional changes in both neurons and glia. To comprehensively map ASD genetic liability across cortical cell types, we conducted a functional genetic burden analysis with 124,416 individuals, including ASD probands and unaffected family members. We examined six classes of rare gene-disrupting variants aggregated across a complete spectrum of transcriptomic cell types of the human prefrontal cortex throughout development. We show that cellular liabilities in ASD delineate a broad and developmentally dynamic architecture. Likewise, we uncover high dependency on classes of variants with Loss-of-Function (LoF) and de novo linked to prenatal cells, while duplications, missense, and inherited variants increase liability through postnatal and glial cell types. Notably, inherited LoF variants uncover the contribution of microglia to ASD liability, also supported by transcriptomic evidence from postmortem ASD brains. Finally, we show that overall, variants disrupting genes differentially expressed in postmortem ASD brains significantly contribute to ASD liability, demonstrating convergence between disrupted transcriptomes and genetic liability. Together, our study offers an integrative, cell-type-aware framework for interpreting ASD risk genetics.

genomics↗

bioRxiv2024

Effects of gene dosage on cognitive ability: A function-based association study across brain and non-brain processes

Genomic Copy Number Variants (CNVs) that increase risk for neurodevelopmental disorders are also associated with lower cognitive ability in general population cohorts. Studies have focussed on a small set of recurrent CNVs, but burden analyses suggested that the vast majority of CNVs affecting cognitive ability are too rare to reach variant-level association. As a result, the full range of gene-dosage-sensitive biological processes linked to cognitive ability remains unknown. To investigate this issue, we identified all CNVs >50 kilobases in 258k individuals from 6 general population cohorts with assessments of general cognitive abilities. We performed a CNV-GWAS and functional burden analyses, which tested 6502 gene-sets defined by tissue and cell-type transcriptomics as well as gene ontology disrupted by all rare coding CNVs. CNV-GWAS identified a novel duplication at 2q12.3 associated with higher performance in cognitive ability. Among the 864 gene-sets associated with cognitive ability, only 11% showed significant effects for both deletions and duplication. Accordingly, we systematically observed negative correlations between deletion and duplication effect sizes across all levels of biological observations. We quantified the preferential effects of deletions versus duplication using tagDS, a new normalized metric. Cognitive ability was preferentially affected by cortical, presynaptic, and negative-regulation gene-sets when duplicated. In contrast, preferential effects of deletions were observed for subcortical, post-synaptic, and positive-regulation gene-sets. A large proportion of gene-sets assigned to non-brain organs were associated with cognitive ability due to low tissue specificity genes, which were associated with higher sensitive to haploinsufficiency. Overall, most biological functions associated with cognitive ability are divided into those sensitive to either deletion or duplications.

genetics↗

bioRxiv2018

Patterns of fish utilisation in a tropical Indo-Pacific mangrove-coral seascape, New Caledonia

Mangrove forests are important habitats for fish. However, their utilisation by fish, and the specific values they confer, are still not fully understood. This study details how fish use mangrove forests in an Indo-Pacific mangrove-coral reef seascape. Sampling was conducted using underwater video cameras (UVCs) to describe spatial and temporal variations in fish assemblages across a small-scale (~ 2.5 km2) system, and over the tidal and lunar cycle. UVCs were deployed in the two main component habitats of mangrove forests: at the mangrove forest edge, and inside the forest (5 m from the forest edge). The patterns of utilisation of fish were established across the tidal and lunar cycle. Proximity to coral reefs had a strong influence on the mangrove fish community, as most fish recorded were reef-associated. Juveniles of 12 reef species were observed, including two species classified as vulnerable on the IUCN list and one endemic species. Fish assemblages on the mangrove edge differed substantially from those inside the forest. Most fish utilised the forest edge with few species making regular use of in- forest habitats, supporting the contention that most fish species remain on the edge and potentially retreat into the forest for opportunistic feeding, or when threatened by larger predators. Species-specific patterns of utilisation varied across the tidal and lunar cycle. Small differences in depth profiles and substrate across the small-scale system had a substantial effect on fish assemblages, highlighting the importance of accounting for spatial heterogeneity in these factors. These data provide important information for managers to implement adequate conservation strategies that includes broader interconnected habitat mosaics.

ecology↗