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McNeill, L.

Publications and source records attributed to McNeill, L..

2 recordsLinked to original sources

synapsis: A Bioconductor package to automate the analysis of meiotic double-strand break repair and crossover formation

SummaryImmunofluorescent staining is commonly used to generate images to characterise cytological phenotypes. The manual quantification of DNA double-strand breaks and their repair intermediates during meiosis using image data requires a series of subjective steps, from image selection to the counting of particular events per nucleus. Here we describe synapsis, a Bioconductor package, which includes a set of functions to automate the process of identifying meiotic nuclei and quantifying key double-strand break formation and repair events in a rapid, scalable and reproducible workflow, and compare it to manual user quantification. The software can be extended for other applications in meiosis research, such as incorporating machine learning approaches to categorise meiotic substages. Availability and implementationsynapsis can be freely downloaded and installed at: http://bioconductor.org/packages/release/bioc/html/synapsis.html R functions and further information can be found at https://gitlab.svi.edu.au/drr-public/synapsis Contactwcrismani@svi.edu.au

cell biology↗

Fancm regulates meiotic double-strand break repair pathway choice in mammals

Meiotic crossovers are required for accurate chromosome segregation and to produce new allelic combinations. Meiotic crossover numbers are tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we describe the tumour suppressor FANCM as a meiotic anti-crossover factor in mammals. Crossover analyses with single-gamete and pedigree datasets both reveal a genome-wide increase in crossover frequencies in Fancm-deficient mice. Gametogenesis is heavily perturbed in Fancm loss of function mice, which is consistent with the reproductive defects reported in humans with biallelic FANCM mutations. A portion of the gametogenesis defects can be attributed to the cGAS-STING pathway. Despite the gametogenesis phenotypes in Fancm mutants both sexes were capable of producing offspring. We propose that the anti-crossover function and role in gametogenesis of Fancm are separable and will inform diagnostic pathways for human genomic instability disorders.

genetics↗