The separation of germ cell populations from the soma is part of the evolutionary transition to multicellularity. Only genetic information present in the germ cells will be inherited by future generations, and any molecular processes affecting the germline genome are therefore likely to be passed on. Despite its prevalence across taxonomic kingdoms, we are only starting to understand details of the underlying micro-evolutionary processes occurring at the germline genome level. These include segregation, recombination, mutation and selection and can occur at any stage during germline differentiation and mitotic germline proliferation to meiosis and post-meiotic gamete maturation. Selection acting on germ cells at any stage from the diploid germ cell to the haploid gametes may cause significant deviations from Mendelian inheritance and may be more widespread than previously assumed. The mechanisms that affect and potentially alter the genomic sequence and allele frequencies in the germline are pivotal to our understanding of heritability. With the rise of new sequencing technologies, we are now able to address some of these unanswered questions. In this review, we comment on the most recent developments in this field and identify current gaps in our knowledge.
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http://dx.doi.org/10.1111/brv.12680 | DOI Listing |
Clin Transl Med
January 2025
Unit of Molecular Biology, Georges-François Leclerc Cancer center, UNICANCER, Dijon, France.
Background: Molecular diagnosis has become highly significant for patient management in oncology.
Methods: Here, 30 well-characterized clinical germline samples were studied with adaptive sampling to enrich the full sequence of 152 cancer predisposition genes. Sequencing was performed on Oxford Nanopore (ONT) R10.
Hum Genomics
January 2025
Population Health Program, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Background: TP53 variant classification benefits from the availability of large-scale functional data for missense variants generated using cDNA-based assays. However, absence of comprehensive splicing assay data for TP53 confounds the classification of the subset of predicted missense and synonymous variants that are also predicted to alter splicing. Our study aimed to generate and apply splicing assay data for a prioritised group of 59 TP53 predicted missense or synonymous variants that are also predicted to affect splicing by either SpliceAI or MaxEntScan.
View Article and Find Full Text PDFCommun Med (Lond)
January 2025
Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.
Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.
Sci Rep
January 2025
Marine Molecular Genetics & Biotechnology Laboratory, Department of Aquaculture, National Taiwan Ocean University, Keelung, 202301, Taiwan.
Primordial germ cells (PGCs), the progenitors of gametes, are essential for teleost reproduction. While their formation is conserved across teleosts, the activation, migration routes, and localization periods vary among species. In this study, we developed a novel transgenic line, Tg(ddx4:TcCFP13-nanos3), based on the Nile tilapia genome, to label PGCs with clear fluorescent signals in the freshwater angelfish (Pterophyllum scalare).
View Article and Find Full Text PDFNature
January 2025
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Germline BRCA2 loss-of function variants, which can be identified through clinical genetic testing, predispose to several cancers. However, variants of uncertain significance limit the clinical utility of test results. Thus, there is a need for functional characterization and clinical classification of all BRCA2 variants to facilitate the clinical management of individuals with these variants.
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