Biology subjects

Fenton, S.

Publications and source records attributed to Fenton, S..

4 recordsLinked to original sources

bioRxiv2025

The historical patterns that have shaped contemporary genetic differentiation across populations of Arctic charr in Scotland

Glacial history is an important contributor to contemporary biogeographic patterns because it caused population fragmentation and consequently diversification. The Arctic charr (Salvelinus alpinus) is a highly diverse non-anadromous salmonid fish species in Britain and Ireland, which likely was anadromous when it colonised around the end of the last ice age. Colonisation history of the species remains largely unexplored and so the potential impact on contemporary patterns of genetic differentiation remains unclear. To address this, we conducted a national-scale genetic study of Arctic charr using a genome-wide dataset of SNPs (24,878 SNPs and 410 individuals) and mitochondrial ND1 sequences (238 sequences). We found several mitochondrial haplotypes were shared across Britain, Ireland, and the wider Holarctic suggesting colonisation by multiple sub-lineages of the Atlantic lineage of the species. Genetic differentiation was not correlated with geographic distance among river catchments, highlighting the effect of spatial isolation and genetic drift. Several populations across different river catchments showed atypical ancestries and evidence for genetic mixing, which we speculate are due to asynchronous ice coverage and the presence of ice-dammed lakes. Our results highlight how glacial history can impact colonisation history and subsequently contemporary patterns of genetic differentiation in this widespread species.

genetics↗

bioRxiv2025

Defining conservation units in a highly diverse species: A case on Arctic charr

Defining appropriate conservation units is crucial to the protection and management of biodiversity. These delineations deliver further benefit when they include assessments of population vulnerability to extinction from pressures such as climate change. However, delineations and vulnerability assessments are particularly difficult within highly diverse species, such as the salmonid fish Arctic charr (Salvelinus alpinus), that show extensive phenotypic and genetic variation within and across locations, variable and complex life histories, and broad geographic distributions. As yet, the nature and scope of Arctic charr diversity has not been characterised at the scale needed to delineate key conservation units in Scotland. To identify evolutionarily significant and vulnerable populations to prioritise for conservation, we conducted a genomic study of Arctic charr populations across Britain and Ireland with a focus on Scottish populations (N=64 populations; 24,878 SNPs; 410 individuals). We found that most lake populations represented distinct genetic clusters, with limited gene flow between them and resulting in substantial genetic differentiation. Higher level groupings of genetic similarity across catchments likely reflect historic anadromy and migration, with populations primarily grouping east or west of the central watershed divide in Scotland. Analysing genetic offset, also known as genomic vulnerability, we identified strong inverse correlations between genetic vulnerability with latitude and distance to the sea suggesting that more southern and more inland populations are more vulnerable to loss due to climate change. Additionally, patterns of vulnerability across several additional metrics identified further populations that may be at high vulnerability to loss. We further used our genetic data, along with phenotypic and geographic information, to identify populations of greatest evolutionary significance. This highlighted the most important ones to protect are those in locations with multiple ecotypes, a key facet of functional Arctic charr biodiversity, and populations that are the only ones in their Hydrometric Area.

genomics↗

bioRxiv2024

A novel approach to digital characterisation of Tertiary Lymphoid Structures in colorectal cancer

Tertiary Lymphoid Structures (TLS) in cancer tissue are potential sites for the organisation of immune responses to cancer, and correlate positively with improved clinical outcomes for patients including in colorectal cancer (CRC). However it has proven challenging to standardise assessment of TLS due to the highly variable appearances of circumscribed domains of TLS within tissue sections. A recent three-dimensional reconstruction of TLS in CRC tissue showed that TLS are often large, multi-lobular structures, suggesting that assessing TLS across whole sections may be necessary to provide an accurate view of TLS activity in a patients tumour. In a pilot study we therefore used whole slide scans of multiplexed immunofluorescence images to characterise TLS from 22 subjects with CRC. Multiplexed staining for CD20, CD3, CD8, FoxP3 and Ki-67 enabled us to identify B-cells, CD8+ T cells, FoxP3- CD4 T-cells, and Foxp3+ CD4 T cells in all sections, and quantify both the presence of these cell subsets in lymphocytic clusters and their degree of proliferation within those clusters. In total we identified 524 lymphocytic clusters with morphology consistent with TLS. The count of TLS domains varied substantially between samples (from 4 to 100, mean 24) as did the proportion of total section area occupied by TLS (0.2%-7.8%) as well as size, morphology and cellular constituents; reflecting the intersection of the section plane with complex 3-dimensional structures. We quantified proliferation of B-cells and T-cell subsets within TLS domains across entire sections and compared to the canonical approach of counting and phenotyping individual TLS domains. The whole-slide approach proved far simpler than the canonical approach, generating digital summaries across our sample set clearly identifying patients with strikingly different levels of immune activity within their TLS. It also allowed us to demonstrate strong correlations between the proliferation of B-cells within CRC TLS and that of T-cell subsets. In summary we find that whole-section digital quantification of immune cell activity within TLS has major advantages over canonical approaches. Such whole-section approaches should accelerate research into correlations between TLS status and clinical outcomes, and ultimately enable standardised clinical tests based on automated analysis of multiplexed images.

cancer biology↗

bioRxiv2019

A combined morphometric and statistical approach to assess non-monotonicity in the developing mammary gland of rats in the CLARITY-BPA study

BackgroundCLARITY-BPA is a rare collaboration of guideline-compliant (core) studies and academic hypothesis-based studies to assess the effects of bisphenol A (BPA).\n\nObjectives1) determine BPAs effects on the developing rat mammary gland using new quantitative and established semi-quantitative methods in two labs, 2) develop a software tool for semi-automatic evaluation of quantifiable aspects of the mammary ductal tree, and 3) compare those methods.\n\nMethodsSprague Dawley rats were exposed to BPA, vehicle, or positive control (ethinyl estradiol, EE2) by oral gavage beginning on gestational day 6 and continuing with direct dosing of the pups after birth. There were two studies; sub-chronic and chronic. The latter used two exposure regimes, one stopping at PND21 the other continuing until tissue harvest. Glands were harvested at multiple time points; whole mounts and histological specimens were analyzed blinded to treatment.\n\nResultsThe subchronic studys semiquantitative analysis revealed no significant differences between control and BPA dose groups at PND21; whereas at PND90 there were significant differences between control and the lowest BPA dose and between control and the lowest EE2 dose in animals in estrus. Quantitative, automatized analysis of the chronic PND21 specimens displayed non-monotonic BPA effects with a breaking point between the 25 and 250g/kg/day doses. This breaking point was confirmed by a global statistical analysis of chronic study animals at PND90 and 6 months analyzed by the quantitative method. The BPA response was different from the EE2 effect for many features.\n\nConclusionsBoth the semiquantitative and the quantitative methods revealed non-monotonic effects of BPA. The quantitative unsupervised analysis used 91 measurements and produced the most striking non-monotonic dose-response curves. At all-time points, lower doses resulted in larger effects, consistent with the core study which revealed a significant increase of mammary adenocarcinoma incidence in the stop-dose animals at the lowest BPA dose tested.

developmental biology↗