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Fitzpatrick, B.

Publications and source records attributed to Fitzpatrick, B..

2 recordsLinked to original sources

Barriers Broken: Genetic Swamping in Restored Brook Trout Populations

Scientists use reintroductions to restore native species to their historical ranges but sometimes can overlook the effects of dispersal on the genetic structure of restored populations. In the Great Smoky Mountains National Park (GRSM), an ambitious reintroduction strategy aims to restore native Brook Trout (Salvelinus fontinalis) populations, which have lost over 75% of their historical habitat within the park. Each restoration requires removing non-native trout and selecting restoration streams with natural barriers to prevent recolonization. Multiple Brook Trout populations are mixed in restoration sites to maximize genetic diversity and to avoid depletion of any single source population. However, a miscommunication during a reintroduction in Anthony Creek, which used three source populations for restoration, inadvertently created an in-situ population genetics study. One segment of the restoration site received fish from all three source populations. However, technicians also unintentionally placed fish from just one source upstream of a natural barrier. Unbeknownst to management, fish from this separate translocation dispersed downstream, potentially altering the desired genetic diversity of the restored population. This study characterizes the genetic changes caused by this unidirectional dispersal. Population genetics theory predicts that such movement leads to genetic swamping. Here, we use genetic and population density data to confirm the directionality of dispersal, estimate the rate of genetic swamping, and assess alternative mitigation strategies. Our results indicate that it is already too late for assisted migration within the restored stream to achieve the intended genetic diversity. Instead introducing additional fish above the second natural barrier would be necessary to equalize the contribution of all three source populations. Understanding the interplay between dispersal behavior and genetic structure is crucial for planning reintroductions and refining conservation strategies for this iconic species.

evolutionary biology↗

A novel role for the HLH protein Inhibitor of Differentiation 4 (ID4) in the DNA damage response in basal-like breast cancer.

Basal-like breast cancer (BLBC) is a poorly characterised, heterogeneous disease. Patients are diagnosed with aggressive, high-grade tumours and often relapse with chemotherapy resistance. Detailed understanding of the molecular underpinnings of this disease is essential to the development of personalised therapeutic strategies. Inhibitor of Differentiation 4 (ID4) is a helix-loop-helix transcriptional regulator required for mammary gland development. ID4 is overexpressed in a subset of BLBC patients, associating with a stem-like poor prognosis phenotype, and is necessary for the growth of cell line models of BLBC, through unknown mechanisms. Here, we have defined a molecular mechanism of action for ID4 in BLBC and the related disease highgrade serous ovarian cancer (HGSOV), by combining RIME proteomic analysis and ChIP-Seq mapping of genomic binding sites. Remarkably, these studies have revealed novel interactions with DNA damage response proteins, in particular, mediator of DNA damage checkpoint protein 1 (MDC1). Through MDC1, ID4 interacts with other DNA repair proteins ({gamma}H2AX and BRCA1) at fragile chromatin sites. ID4 does not affect transcription at these sites, instead binding to chromatin following DNA damage and regulating DNA damage signalling. Clinical analysis demonstrates that ID4 is amplified and overexpressed at a higher frequency in BRCA1-mutant BLBC compared with sporadic BLBC, providing genetic evidence for an interaction between ID4 and DNA damage repair pathways. These data link the interactions of ID4 with MDC1 to DNA damage repair in the aetiology of BLBC and HGSOV.

cancer biology↗