Biology subjects

Lamaze, F. C.

Publications and source records attributed to Lamaze, F. C..

3 recordsLinked to original sources

bioRxiv2024

Spleen gene expression is associated with mercury content in three-spined stickleback populations

Mercury can be very toxic at low environmental concentrations by impairing immunological, neurological, and other vital pathways in humans and animals. Aquatic ecosystems are heavily impacted by mercury pollution, with evidence of biomagnification through the food web. We examined the effect of mercury toxicity on the spleen, one of the primary immune organs in fish, in natural populations of the three-spined stickleback (Gasterosteus aculeatus Linnaeus, 1758). Our aim was to better understand adaptation to high mercury environments by investigating transcriptomic changes in the spleen. Three stickleback populations with mean Hg muscle concentrations above and three populations with mean Hg muscle concentrations below the European Biota Quality Standard of 20 ng/g wet weight were selected from the Scheldt and Meuse basin in Belgium. We then conducted RNA sequencing of the spleen tissue of 22 females from these populations. We identified 136 differentially expressed genes between individuals from populations with high and low mean mercury content. The 129 genes that were upregulated were related to the neurological system, immunological activity, hormonal regulation, and inorganic cation transporter activity. Seven genes were downregulated and were all involved in pre-mRNA splicing. The results are indicative of our ability to detect molecular alterations in natural populations that exceed an important environmental quality standard. This allows us to assess the biological relevance of such standards, offering an opportunity to better describe and manage mercury-associated environmental health risks in aquatic populations.

ecology↗

bioRxiv2017

Pan-cancer study of heterogeneous RNA aberrations

We present the most comprehensive catalogue of cancer-associated gene alterations through characterization of tumor transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes project. Using matched whole-genome sequencing data, we attributed RNA alterations to germline and somatic DNA alterations, revealing likely genetic mechanisms. We identified 444 associations of gene expression with somatic non-coding single-nucleotide variants. We found 1,872 splicing alterations associated with somatic mutation in intronic regions, including novel exonization events associated with Alu elements. Somatic copy number alterations were the major driver of total gene and allele-specific expression (ASE) variation. Additionally, 82% of gene fusions had structural variant support, including 75 of a novel class called \"bridged\" fusions, in which a third genomic location bridged two different genes. Globally, we observe transcriptomic alteration signatures that differ between cancer types and have associations with DNA mutational signatures. Given this unique dataset of RNA alterations, we also identified 1,012 genes significantly altered through both DNA and RNA mechanisms. Our study represents an extensive catalog of RNA alterations and reveals new insights into the heterogeneous molecular mechanisms of cancer gene alterations.

genomics↗

bioRxiv2017

Motif Disruption Domains Lead To Cancer Gene Expression Rewiring

Somatic mutations accumulate in non-coding regions of the genome during tumorigenesis, but their functional characterization presents a challenge. Somatic non-coding mutations rarely overlap among patients, which necessitates large sample sizes to detect associations. We analysed somatic mutations called from whole-genome sequencing (WGS) and RNA sequencing (RNAseq) from 3000 tumors across the Pan-Cancer Analysis of Whole Genomes to identify and functionally characterize mutation accumulation and its impact on gene dysregulation in cancer. We identified 1.5 million motif disruption domains (MDDs) across 40 cancer types, which we characterized as pan-cancer targets for recurrent mutation accumulation. These MDDs deregulate gene expression in cancer-specific and pan-cancer patterns by disrupting transcription factor binding sites in regulatory and insulator elements. Disruption is most recurrent across individuals at MDDs in conserved open chromatin, revealing potential drivers. This accumulation of somatic variants targeting regulatory and structural elements in MDDs generates gene expression dysregulation during tumorigenesis.

cancer biology↗