DNA repair function scores for 2172 variants in the BRCA1 amino-terminus
In this study, we have re-assessed the data from this multiplexed assay using an improved analysis pipeline. These new analysis methods yield functional scores for more variants in the first 192 amino acids of BRCA1, plus we report new results for BRCA1 amino a cid residues 193–302. We now present the functional classification of 2172 BRCA1 variants in BRCA1 residues 2–302 using the multiplexed HDR assay. Comparison of the functional determinations of the missense variants with clinically known benign or pathogenic variants indicated 93% sensitivity an d 100% specificity for this assay. The results fromBRCA1 variants t...
Source: PLoS Genetics - August 14, 2023 Category: Genetics & Stem Cells Authors: Mariame Diabate Source Type: research
Drosophila embryos allocate lipid droplets to specific lineages to ensure punctual development and redox homeostasis
by Marcus D. Kilwein, T. Kim Dao, Michael A. Welte
Lipid droplets (LDs) are ubiquitous organelles that facilitate neutral lipid storage in cells, including energy-dense triglycerides. They are found in all investigated metazoan embryos where they are thought to provide energy for development. Intriguingly, early embryos of diverse metazoan species asymmetrically allocate LDs amongst cellular lineages, a process which can involve massive intracellular redistribution of LDs. However, the biological reason for asymmetric lineage allocation is unknown. To address this issue, we utilize the Drosophila embryo where the cytoskel...
Source: PLoS Genetics - August 14, 2023 Category: Genetics & Stem Cells Authors: Marcus D. Kilwein Source Type: research
Exome sequencing identified rare recurrent copy number variants and hereditary breast cancer susceptibility
by Timo A. Kumpula, Sandra Vorimo, Taneli T. Mattila, Luke O ’Gorman, Galuh Astuti, Anna Tervasmäki, Susanna Koivuluoma, Tiina M. Mattila, Mervi Grip, Robert Winqvist, Outi Kuismin, Jukka Moilanen, Alexander Hoischen, Christian Gilissen, Tuomo Mantere, Katri Pylkäs
Copy number variants (CNVs) are a major source of genetic variation and can disrupt genes or affect gene dosage. They are known to be causal or underlie predisposition to various diseases. However, the role of CNVs in inherited breast cancer susceptibility has not been thoroughly investigated. To address this, we performed whole-exome sequencing based analy...
Source: PLoS Genetics - August 14, 2023 Category: Genetics & Stem Cells Authors: Timo A. Kumpula Source Type: research
Matriptase-dependent epidermal pre-neoplasm in zebrafish embryos caused by a combination of hypotonic stress and epithelial polarity defects
by Julia Hatzold, Verena Nett, Stephanie Brantsch, Jin-Li Zhang, Joy Armistead, Heike Wessendorf, Rebecca Stephens, Patrick O. Humbert, Sandra Iden, Matthias Hammerschmidt
Aberrantly up-regulated activity of the type II transmembrane protease Matriptase-1 has been associated with the development and progression of a range of epithelial-derived carcinomas, and a variety of signaling pathways can mediate Matriptase-dependent tumorigenic events. During mammalian carcinogenesis, gain of Matriptase activity often results from imbalanced ratios between Matriptase and its cognate transmembrane inhibitor Hai1. Similarly, in zebra...
Source: PLoS Genetics - August 11, 2023 Category: Genetics & Stem Cells Authors: Julia Hatzold Source Type: research
Systematic analysis of < i > tup1 < /i > and < i > cyc8 < /i > mutants reveals distinct roles for < i > TUP1 < /i > and < i > CYC8 < /i > and offers new insight into the regulation of gene transcription by the yeast Tup1-Cyc8 complex
We examinedTUP1 andCYC8 single and double deletion mutants and show thatCYC8 represses more genes thanTUP1, and that there are genes subject to (i) unique repression byTUP1 orCYC8, (ii) redundant repression byTUP1 andCYC8, and (iii) there are genes at which de-repression in acyc8 mutant is dependent uponTUP1, and vice-versa. We also reveal that Tup1p and Cyc8p can make distinct contributions to commonly repressed genes most likely via specific interactions with different histone deacetylases. Furthermore, we show that Tup1p and Cyc8p can be found independently of each other to negatively regulate gene transcription and can...
Source: PLoS Genetics - August 11, 2023 Category: Genetics & Stem Cells Authors: Brenda Lee Source Type: research
