Biology subjects

Clarke, C. L.

Publications and source records attributed to Clarke, C. L..

3 recordsLinked to original sources

bioRxiv2025

Environment shapes the association between the skin microbiome and infection dynamics of the Dermocystid pathogen Amphibiothecum in Palmate newts (Lissotriton helveticus).

Infectious diseases are a leading cause of biodiversity declines, but the factors shaping the prevalence and intensity of wildlife disease outbreaks remain unresolved. Host-associated microbes are likely a key component of host resistance to infection, but a hosts ability to recruit such protective microbes may be restricted by the availability of microbes present in their immediate environment. Here we investigate the associations between the abiotic environment, skin microbiome, and infection with the Dermocystid pathogen Amphibiothecum meredithae in Palmate newts (Lissotriton helveticus) on the Isle of Rum, Scotland. We found more acidic ponds to be associated with higher skin microbiome diversity and lower pathogen prevalence. Predicted functional analysis of microbiota composition identified bacterially-mediated pathways linked to host immunity upregulated in skin microbiotas associated with more acidic ponds and lower infection prevalence. This study highlights the potential importance of the environment in modulating host- microbiome-pathogen relationships and patterns of infection in the wild.

ecology↗

bioRxiv2021

Rare copy number variants (CNVs) and breast cancer risk

BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.

genetics↗

bioRxiv2019

Common breast cancer risk loci predispose to distinct tumor subtypes

BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER), but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate <5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at P<0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

genetics↗