Catherine Laprise

Rare diseases represent a major public health challenge because they are often associated with severe phenotypes, yet many causal variants remain undiscovered. Founder populations provide a unique opportunity to identify disease-causing variants through the local enrichment of rare alleles. Using whole-genome sequencing data from individuals in the Saguenay-Lac-Saint-Jean population, enriched variants were identified and their founder status was assessed through identity-by-descent sharing. Variant impact was evaluated using functional prediction tools without relying on prior clinical classification. A total of 131 founder variants of interest were identified, most of which would likely have been overlooked by conventional approaches based on existing clinical annotations. We developed a web-based platform that facilitates clinician access to the latest interpretation of their genetic variants of interest. These findings demonstrate that potentially pathogenic variants can remain undetected even in extensively studied founder populations. More broadly, they highlight the value of population structure-based approaches for uncovering rare disease variants and improving the characterization of genetic disease risk across human populations.

Urban vegetation varies with socio-economic gradients, as lower-income neighborhoods often host sparser and less diverse green spaces. This disparity may affect respiratory health by influencing exposure to bioaerosols. Understanding the characteristics of this aerobiome could help anticipate risks related to allergies and other respiratory conditions. Here, we hypothesized that urban vegetation cover and socio-economic status shape urban bioaerosols. We sampled bioaerosols at 65 sites across three Canadian cities of varying population size and density using an active air sampler over four months, and characterized their bacterial, fungal, and pollen composition using amplicon sequencing. Seasonal alpha diversity varied significantly for fungi and pollen. Based on beta diversity, sampling period alone explained up to 40% of pollen, 29% of fungal, and 11% of bacterial community composition variation. In contrast, vegetation cover explained only a minor portion of the variance in bioaerosol composition, and median household income, almost none. These findings provide a critical baseline for understanding the urban aerobiome and highlight the need to study how vegetation identity and diversity, rather than cover alone, may shape bioaerosol dynamics in cities. As cities grow and urban greening initiatives expand, demystifying the aerobiome dynamics becomes an urgent public health priority.

Food allergy (FA) is a great public health concern with an increased prevalence in the last decades. The underlying development mechanisms of FA and food sensitization (FS), which represents the first stage of development of FA, are influenced by environmental, epigenetic, and genetic factors. DNA methylation is an important epigenetic mediator of gene-environment interactions and key to understanding these mechanisms. Studies have linked whole-genome DNA methylation profile to FA and FS, but they all use methylation arrays. Methylation sequencing captures target regions of methylome with an extensive coverage. Thus, our objective was to identify CpG sites in genome-wide immune regulatory regions associated with FS and test their association with genetic variants using methylation quantitative trait loci (mQTL) analysis in French-Canadian individuals. In 114 individuals from the Saguenay-Lac-Saint-Jean asthma family cohort, a total of 10 CpG sites out of 5,233,004 CpG sites were associated with the FS status (P < 1 × 10^-8). CpG sites were located in 10 genes (ARRDC1, B9D1, CFL1, CROCC, DHX36, DND1, PMS1, RASSF1, TOP2A, and USP21) all of which were associated with immune response and allergic diseases (allergy, asthma, atopic dermatitis, and allergic rhinitis) in the literature. Almost all individuals with FS clustered based on the methylation levels of these CpG sites which reinforces their importance and relevance to discriminate individuals with and without FS in our cohort. Among the top 10 most significant CpG sites, five were associated with 478 genetic variants in trans-mQTL (FDR < 1 × 10^-8). To our knowledge, this is a unique association study between FS and DNA methylation using targeted bisulfite sequencing across the genome. This approach provides high-resolution assessment of genome-wide functional methylome that yields valuable understandings to this field of research. The results reveal potential relationships between FS, CpG sites, and genetic variants located in genes involved in allergic diseases. This provides potential insights on the underlying effects of DNA methylation and genetic variants on FS and possibly the pathogenesis of FA. Further epigenome-wide studies on larger samples combined with genome-wide genotyping are needed to validate the results and verify the biological potential of these CpG sites.

Background: Food allergies (FAs) are an increasing public health concern, particularly in children. Oral immunotherapy (OIT) is an emerging treatment strategy under clinical investigation for desensitization of children with FA to food allergens. Dysbiosis of the gut microbiota has been implicated in FAs, and various factors influence its composition; however, the impact of OIT on the gut microbiota remains largely unexplored.Objective: This study aimed to identify the changes in diversity of the gut microbiota following OIT in children with FA.Methods: Thirty children with FA (mean age 3.93 years, age range 2.00–14.00) undergoing oral immunotherapy targeting legumes (lentils, peanuts, peas), tree nuts (cashews, hazelnuts, pistachios), animal products (milk, egg), and fish and shellfish (salmon, shrimp), as well as seven non‐allergic controls (mean age 2.65 years, age range 0.25–5.00) participated in this study. Fecal samples were collected before and after OIT from children with FA, and once from controls. The gut microbiota was profiled using 16S rRNA sequencing, followed by diversity and differential abundance analyses. Alpha and beta diversities were compared, and differential abundance was assessed.Results: Beta diversity analysis revealed small but significant differences in microbial composition between children with FA before and after OIT, and between controls and children with FA before OIT. Differential abundance analysis showed that OIT induced a reversion of the abundance levels of Bacteroidota and Verrucomicrobiota toward those observed in controls.Conclusion: To our knowledge, this is the first study to investigate the impact of OIT on the gut microbiota in children with different FAs for identifying potential microbial biomarkers and convincingly demonstrated their interrelation. These findings may help improve and personalize FA treatment.

Background: Food allergies (FAs) are an increasing public health concern, particularly in children. Oral immunotherapy (OIT) is an emerging treatment strategy under clinical investigation for desensitization of children with FA to food allergens. Dysbiosis of the gut microbiota has been implicated in FAs, and various factors influence its composition; however, the impact of OIT on the gut microbiota remains largely unexplored. Objective: This study aimed to identify the changes in diversity of the gut microbiota following OIT in children with FA. Methods: Thirty children with FA undergoing oral immunotherapy and seven non-allergic controls participated in this study. Fecal samples were collected before and after OIT from children with FA, and once from controls. The gut microbiota was profiled using 16S rRNA sequencing, followed by diversity and differential abundance analyses. Alpha and beta diversities were compared, and differential abundance was assessed. Results: Beta diversity analysis revealed small but significant differences in microbial composition between children with FA before and after OIT, and between controls and children with FA before OIT. Differential abundance analysis showed that OIT induced a reversion of the abundance levels of Bacteroidota and Verrucomicrobiota towards those observed in controls. Conclusion: To our knowledge, this is the first study to investigate the impact of OIT on the gut microbiota in children with different FAs for identifying potential microbial biomarkers, and convincingly demonstrated their interrelation. These findings may help improve and personalize FA treatment.