Artificial selection reveals complex genetic architecture of shoot branching and its response to nitrate supply in Arabidopsis
by Hugo Tavares, Anne Readshaw, Urszula Kania, Maaike de Jong, Raj K. Pasam, Hayley McCulloch, Sally Ward, Liron Shenhav, Elizabeth Forsyth, Ottoline Leyser
Quantitative traits may be controlled by many loci, many alleles at each locus, and subject to genotype-by-environment interactions, making them difficult to map. One example of such a complex trait is shoot branching in the model plant Arabidopsis, and its plasticity in response to nitrate. Here, we use artificial selection under contrasting nitrate supplies to dissect the genetic architecture of this complex trait, where loci identified by association mapping failed...
Source: PLoS Genetics - August 24, 2023 Category: Genetics & Stem Cells Authors: Hugo Tavares Source Type: research
Neutrophil extracellular trap formation and gene programs distinguish TST/IGRA sensitization outcomes among < i > Mycobacterium tuberculosis < /i > exposed persons living with HIV
by Elouise E. Kroon, Wilian Correa-Macedo, Rachel Evans, Allison Seeger, Lize Engelbrecht, Jurgen A. Kriel, Ben Loos, Naomi Okugbeni, Marianna Orlova, Pauline Cassart, Craig J. Kinnear, Gerard C. Tromp, Marlo M öller, Robert J. Wilkinson, Anna K. Coussens, Erwin Schurr, Eileen G. Hoal
Persons living with HIV (PLWH) have an increased risk for tuberculosis (TB). After prolonged and repeated exposure, some PLWH never develop TB and show no evidence of immune sensitization toMycobacterium tuberculosis (Mtb) as defined by persistently negative tuberculin skin tests (TST) and interferon gamma release assays (IGRA). This group ...
Source: PLoS Genetics - August 24, 2023 Category: Genetics & Stem Cells Authors: Elouise E. Kroon Source Type: research
Beyond a PPR-RNA recognition code: Many aspects matter for the multi-targeting properties of RNA editing factor PPR56
by Yingying Yang, Kira Ritzenhofen, Jessica Otrzonsek, Jingchan Xie, Mareike Schallenberg-R üdinger, Volker Knoop
The mitochondrial C-to-U RNA editing factor PPR56 of the mossPhyscomitrium patens is an RNA-binding pentatricopeptide repeat protein equipped with a terminal DYW-type cytidine deaminase domain. Transferred intoEscherichia coli, PPR56 works faithfully on its two native RNA editing targets, nad3eU230SL and nad4eU272SL, and also converts cytidines into uridines at over 100 off-targets in the bacterial transcriptome. Accordingly, PPR56 is attractive for detailed mechanistic studies in the heterologous bacterial s...
Source: PLoS Genetics - August 21, 2023 Category: Genetics & Stem Cells Authors: Yingying Yang Source Type: research
Muscleblind-1 interacts with tubulin mRNAs to regulate the microtubule cytoskeleton in < i > C < /i > . < i > elegans < /i > mechanosensory neurons
by Dharmendra Puri, Sunanda Sharma, Sarbani Samaddar, Sruthy Ravivarma, Sourav Banerjee, Anindya Ghosh-Roy
Regulation of the microtubule cytoskeleton is crucial for the development and maintenance of neuronal architecture, and recent studies have highlighted the significance of regulated RNA processing in the establishment and maintenance of neural circuits. In a genetic screen conducted using mechanosensory neurons ofC.elegans, we identified a mutation inmuscleblind-1/mbl-1 as a suppressor of loss of kinesin-13 family microtubule destabilizing factorklp-7. Muscleblind-1(MBL-1) is an RNA-binding protein that regulates the...
Source: PLoS Genetics - August 21, 2023 Category: Genetics & Stem Cells Authors: Dharmendra Puri Source Type: research
Kar4, the yeast homolog of METTL14, is required for mRNA m < sup > 6 < /sup > A methylation and meiosis
by Zachory M. Park, Abigail J. Sporer, Katherine Kraft, Krystal K. Lum, Edith Blackman, Ethan Belnap, Christopher M. Yellman, Mark D. RoseKAR4, the yeast homolog of the mammalian mRNA N6A-methyltransferase complex componentMETTL14, is required for two disparate developmental programs inSaccharomyces cerevisiae: mating and meiosis. To understandKAR4’s role in yeast mating and meiosis, we used a genetic screen to isolate 25 function-specific mutant alleles, which map to non-overlapping surfaces on a predicted structure of the Kar4 protein (Kar4p). Most of the mating-specific alleles (Mat-) abolish Kar4p ’s interaction wi...
Source: PLoS Genetics - August 21, 2023 Category: Genetics & Stem Cells Authors: Zachory M. Park Source Type: research
Regulation of chromatin accessibility and gene expression in the developing hippocampal primordium by LIM-HD transcription factor LHX2
We examined transcriptomic and chromatin-level features that distinguish the Hcp from the Ncp in the mouse during the early neurogenic period, embryonic day (E)12.5. ATAC-seq revealed that the Hcp was more accessible than the Ncp at this stage. Motif analysis of the differentially accessible loci in these tissues revealed LHX2 as a candidate transcription factor for modulating gene regulatory networks (GRNs). We analyzed LHX2 occupancy profiles and compared these with transcriptomic data from control andLhx2 mutant Hcp and Ncp at E12.5. Our results revealed that LHX2 directly regulates distinct genes in the Hcp and Ncp wit...
Source: PLoS Genetics - August 18, 2023 Category: Genetics & Stem Cells Authors: Varun Suresh Source Type: research
Multi-ancestry GWAS analysis identifies two novel loci associated with diabetic eye disease and highlights < i > APOL1 < /i > as a high risk locus in patients with diabetic macular edema
by Amy D. Stockwell, Michael C. Chang, Anubha Mahajan, William Forrest, Neha Anegondi, Rion K. Pendergrass, Suresh Selvaraj, Jens Reeder, Eric Wei, VA Iglesias, Natalie M. Creps, Laura Macri, Andrea N. Neeranjan, Marcel P. van der Brug, Suzie J. Scales, Mark I. McCarthy, Brian L. Yaspan
Diabetic retinopathy (DR) is a common complication of diabetes. Approximately 20% of DR patients have diabetic macular edema (DME) characterized by fluid leakage into the retina. There is a genetic component to DR and DME risk, but few replicable loci. Because not all DR cases have DME, we focused on DME to increase power, and conducted a ...
Source: PLoS Genetics - August 16, 2023 Category: Genetics & Stem Cells Authors: Amy D. Stockwell Source Type: research
Functional mapping of N-terminal residues in the yeast proteome uncovers novel determinants for mitochondrial protein import
by Salom é Nashed, Houssam El Barbry, Médine Benchouaia, Angélie Dijoux-Maréchal, Thierry Delaveau, Nadia Ruiz-Gutierrez, Lucie Gaulier, Déborah Tribouillard-Tanvier, Guillaume Chevreux, Stéphane Le Crom, Benoit Palancade, Frédéric Devaux, Elodie Laine, Mathilde Garcia
N-terminal ends of polypeptides are critical for the selective co-translational recruitment of N-terminal modification enzymes. However, it is unknown whether specific N-terminal signatures differentially regulate protein fate according to their cellular functions. In this work, we developed anin-silico approach to detect functional preferences in c...
Source: PLoS Genetics - August 16, 2023 Category: Genetics & Stem Cells Authors: Salom é Nashed Source Type: research
Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context
by Thomas W. Willis, Chris Wallace
Assessment of the genetic similarity between two phenotypes can provide insight into a common genetic aetiology and inform the use of pleiotropy-informed, cross-phenotype analytical methods to identify novel genetic associations. The genetic correlation is a well-known means of quantifying and testing for genetic similarity between traits, but its estimates are subject to comparatively large sampling error. This makes it unsuitable for use in a small-sample context. We discuss the use of a previously published nonparametric test of genetic similarity for application to GWAS summary stati...
Source: PLoS Genetics - August 16, 2023 Category: Genetics & Stem Cells Authors: Thomas W. Willis Source Type: research
Genomic diversity landscapes in outcrossing and selfing < i > Caenorhabditis < /i > nematodes
by Anastasia A. Teterina, John H. Willis, Matt Lukac, Richard Jovelin, Asher D. Cutter, Patrick C. PhillipsCaenorhabditis nematodes form an excellent model for studying how the mode of reproduction affects genetic diversity, as some species reproduce via outcrossing whereas others can self-fertilize. Currently, chromosome-level patterns of diversity and recombination are only available for self-reproducingCaenorhabditis, making the generality of genomic patterns across the genus unclear given the profound potential influence of reproductive mode. Here we present a whole-genome diversity landscape, coupled with a new geneti...
Source: PLoS Genetics - August 16, 2023 Category: Genetics & Stem Cells Authors: Anastasia A. Teterina Source Type: research
Integrating sex-bias into studies of archaic introgression on chromosome X
by Elizabeth T. Chevy, Emilia Huerta-S ánchez, Sohini Ramachandran
Evidence of interbreeding between archaic hominins and humans comes from methods that infer the locations of segments of archaic haplotypes, or ‘archaic coverage’ using the genomes of people living today. As more estimates of archaic coverage have emerged, it has become clear that most of this coverage is found on the autosomes— very little is retained on chromosome X. Here, we summarize published estimates of archaic coverage on auto somes and chromosome X from extant human samples. We find on average 7 times more archaic coverage on autosomes than...
Source: PLoS Genetics - August 14, 2023 Category: Genetics & Stem Cells Authors: Elizabeth T. Chevy Source Type: research
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
