Bayesian approach to assessing population differences in genetic risk of disease with application to prostate cancer
by Iain R. Timmins, The PRACTICAL Consortium , Frank Dudbridge
Population differences in risk of disease are common, but the potential genetic basis for these differences is not well understood. A standard approach is to compare genetic risk across populations by testing for mean differences in polygenic scores, but existing studies that use this approach do not account for statistical noise in effect estimates (i.e., the GWAS betas) that arise due to the finite sample size of GWAS training data. Here, we show using Bayesian polygenic score methods that the level of uncertainty in estimates of genetic risk differences acr...
Source: PLoS Genetics - April 17, 2024 Category: Genetics & Stem Cells Authors: Iain R. Timmins Source Type: research
The quantitative genetics of gene expression in Mimulus guttatus
by Paris Veltsos, John K. Kelly
Gene expression can be influenced by genetic variants that are closely linked to the expressed gene (cis eQTLs) and variants in other parts of the genome (trans eQTLs). We created a multiparental mapping population by sampling genotypes from a single natural population ofMimulus guttatus and scored gene expression in the leaves of 1,588 plants. We find that nearly every measured gene exhibits cis regulatory variation (91% have FDR (Source: PLoS Genetics)
Source: PLoS Genetics - April 11, 2024 Category: Genetics & Stem Cells Authors: Paris Veltsos Source Type: research
Into the Wild: A novel wild-derived inbred strain resource expands the genomic and phenotypic diversity of laboratory mouse models
by Beth L. Dumont, Daniel M. Gatti, Mallory A. Ballinger, Dana Lin, Megan Phifer-Rixey, Michael J. Sheehan, Taichi A. Suzuki, Lydia K. Wooldridge, Hilda Opoku Frempong, Raman Akinyanju Lawal, Gary A. Churchill, Cathleen Lutz, Nadia Rosenthal, Jacqueline K. White, Michael W. Nachman
The laboratory mouse has served as the premier animal model system for both basic and preclinical investigations for over a century. However, laboratory mice capture only a subset of the genetic variation found in wild mouse populations, ultimately limiting the potential of classical inbred strains to uncover phenotype-associated variants and p...
Source: PLoS Genetics - April 10, 2024 Category: Genetics & Stem Cells Authors: Beth L. Dumont Source Type: research
Genetic interaction mapping reveals functional relationships between peptidoglycan endopeptidases and carboxypeptidases
by Manuela Alvarado Obando, Diego Rey-Varela, Felipe Cava, Tobias D örr
Peptidoglycan (PG) is the main component of the bacterial cell wall; it maintains cell shape while protecting the cell from internal osmotic pressure and external environmental challenges. PG synthesis is essential for bacterial growth and survival, and a series of PG modifications are required to allow expansion of the sacculus. Endopeptidases (EPs), for example, cleave the crosslinks between adjacent PG strands to allow the incorporation of newly synthesized PG. EPs are collectively essential for bacterial growth and must likely be carefully regula...
Source: PLoS Genetics - April 10, 2024 Category: Genetics & Stem Cells Authors: Manuela Alvarado Obando Source Type: research
A small-molecule approach to restore female sterility phenotype targeted by a homing suppression gene drive in the fruit pest < i > Drosophila suzukii < /i >
In this study, we constructed a 3-gRNA homing gene drive system targeting the recessive female fertility geneTyrosine decarboxylase 2 (Tdc2) inDrosophila suzukii, a notorious fruit pest. Our investigation revealed only a low level of homing in the germline, but feeding octopamine restored the egg-laying defects inTdc2 mutant females, allowing easier line maintenance than for other suppression drive targets. We tested the effectiveness of a similar system inDrosophila melanogaster and constructed additional split drive systems by introducing promoter-Cas9 transgenes to improve homing efficiency. Our findings show that genet...
Source: PLoS Genetics - April 5, 2024 Category: Genetics & Stem Cells Authors: Suhan Ma Source Type: research
Belt and braces: Two escape ways to maintain the cassette reservoir of large chromosomal integrons
by Egill Richard, Baptiste Darracq, Eloi Littner, Gael A. Millot, Valentin Conte, Thomas Cokelaer, Jan Engelst ädter, Eduardo P. C. Rocha, Didier Mazel, Céline Loot
Integrons are adaptive devices that capture, stockpile, shuffle and express gene cassettes thereby sampling combinatorial phenotypic diversity. Some integrons called sedentary chromosomal integrons (SCIs) can be massive structures containing hundreds of cassettes. Since most of these cassettes are non-expressed, it is not clear how they remain stable over long evolutionary timescales. Recently, it was found that the experimental inversion of the SCI ofVibrio...
Source: PLoS Genetics - April 5, 2024 Category: Genetics & Stem Cells Authors: Egill Richard Source Type: research
Genomic analyses of < i > Symbiomonas scintillans < /i > show no evidence for endosymbiotic bacteria but does reveal the presence of giant viruses
by Anna Cho, Gordon Lax, Samuel J. Livingston, Yumiko Masukagami, Mariia Naumova, Olivia Millar, Filip Husnik, Patrick J. KeelingSymbiomonas scintillans Guillou et Chr étiennot-Dinet, 1999 is a tiny (1.4 μm) heterotrophic microbial eukaryote. The genus was named based on the presence of endosymbiotic bacteria in its endoplasmic reticulum, however, like most such endosymbionts neither the identity nor functional association with its host were known. We generated both amplification-free shotgun metagenomics and whole genome amplification sequencing data fromS.scintillans strains RCC257 and RCC24, but were unable to detect ...
Source: PLoS Genetics - April 1, 2024 Category: Genetics & Stem Cells Authors: Anna Cho Source Type: research
Kombucha Tea-associated microbes remodel host metabolic pathways to suppress lipid accumulation
by Rachel N. DuMez-Kornegay, Lillian S. Baker, Alexis J. Morris, Whitney L. M. DeLoach, Robert H. Dowen
The popularity of the ancient, probiotic-rich beverage Kombucha Tea (KT) has surged in part due to its purported health benefits, which include protection against metabolic diseases; however, these claims have not been rigorously tested and the mechanisms underlying host response to the probiotics in KT are unknown. Here, we establish a reproducible method to maintainC.elegans on a diet exclusively consisting of Kombucha Tea-associated microbes (KTM), which mirrors the microbial community found in the fermenting culture...
Source: PLoS Genetics - March 28, 2024 Category: Genetics & Stem Cells Authors: Rachel N. DuMez-Kornegay Source Type: research
A natural bacterial pathogen of < i > C < /i > . < i > elegans < /i > uses a small RNA to induce transgenerational inheritance of learned avoidance
by Titas Sengupta, Jonathan St. Ange, Rachel Kaletsky, Rebecca S. Moore, Renee J. Seto, Jacob Marogi, Cameron Myhrvold, Zemer Gitai, Coleen T. MurphyC.elegans can learn to avoid pathogenic bacteria through several mechanisms, including bacterial small RNA-induced learned avoidance behavior, which can be inherited transgenerationally. Previously, we discovered that a small RNA from a clinical isolate ofPseudomonas aeruginosa, PA14, induces learned avoidance and transgenerational inheritance of that avoidance inC.elegans.Pseudomonas aeruginosa is an important human pathogen, and there are otherPseudomonads inC.elegans ’ na...
Source: PLoS Genetics - March 28, 2024 Category: Genetics & Stem Cells Authors: Titas Sengupta Source Type: research
< i > Dmrt1 < /i > is the only male pathway gene tested indispensable for sex determination and functional testis development in tilapia
by Shuangshuang Qi, Shengfei Dai, Xin Zhou, Xueyan Wei, Ping Chen, Yuanyuan He, Thomas D. Kocher, Deshou Wang, Minghui Li
Sex is determined by multiple factors derived from somatic and germ cells in vertebrates. We have identifiedamhy,dmrt1,gsdf as male andfoxl2,foxl3,cyp19a1a as female sex determination pathway genes in Nile tilapia. However, the relationship among these genes is largely unclear. Here, we found that the gonads ofdmrt1;cyp19a1a double mutants developed as ovaries or underdeveloped testes with no germ cells irrespective of their genetic sex. In addition, the gonads ofdmrt1;cyp19a1a;cyp19a1b triple mutants ...
Source: PLoS Genetics - March 27, 2024 Category: Genetics & Stem Cells Authors: Shuangshuang Qi Source Type: research
Correction: Tissue-specific and < i > cis < /i > -regulatory changes underlie parallel, adaptive gene expression evolution in house mice
by The PLOS Genetics Staff (Source: PLoS Genetics)
Source: PLoS Genetics - March 27, 2024 Category: Genetics & Stem Cells Authors: The PLOS Genetics Staff Source Type: research
< i > Spoink < /i > , a LTR retrotransposon, invaded < i > D. melanogaster < /i > populations in the 1990s
by Riccardo Pianezza, Almor ò Scarpa, Prakash Narayanan, Sarah Signor, Robert Kofler
During the last few centuriesD. melanogaster populations were invaded by several transposable elements, the most recent of which was thought to be theP-element between 1950 and 1980. Here we describe a novel TE, which we namedSpoink, that has invadedD. melanogaster. It is a 5216nt LTR retrotransposon of the Ty3/gypsy superfamily. Relying on strains sampled at different times during the last century we show thatSpoink invaded worldwideD. melanogaster populations after theP-element between 1983 and 1993. This invasion was likely triggered ...
Source: PLoS Genetics - March 26, 2024 Category: Genetics & Stem Cells Authors: Riccardo Pianezza Source Type: research
Compartment specific responses to contractility in the small intestinal epithelium
This study reveals the complex and diverse responses of different intestinal epithelial cells to contractility and provides important insight into mechanical regulation of intestinal physiology. (Source: PLoS Genetics)
Source: PLoS Genetics - March 22, 2024 Category: Genetics & Stem Cells Authors: Taylor Hinnant Source Type: research
Canadian COVID-19 host genetics cohort replicates known severity associations
by Elika Garg, Paola Arguello-Pascualli, Olga Vishnyakova, Anat R. Halevy, Samantha Yoo, Jennifer D. Brooks, Shelley B. Bull, France Gagnon, Celia M. T. Greenwood, Rayjean J. Hung, Jerald F. Lawless, Jordan Lerner-Ellis, Jessica K. Dennis, Rohan J. S. Abraham, Jean-Michel Garant, Bhooma Thiruvahindrapuram, Steven J. M. Jones, CGEn HostSeq Initiative , Lisa J. Strug, Andrew D. Paterson, Lei Sun, Lloyd T. Elliott
The HostSeq initiative recruited 10,059 Canadians infected with SARS-CoV-2 between March 2020 and March 2023, obtained clinical information on their disease experience and whole genome sequenced (WGS) their DNA. We...
Source: PLoS Genetics - March 22, 2024 Category: Genetics & Stem Cells Authors: Elika Garg Source Type: research
Opticool: Cutting-edge transgenic optical tools
by Kelli D. Fenelon, Julia Krause, Theodora Koromila
Only a few short decades have passed since the sequencing of GFP, yet the modern repertoire of transgenically encoded optical tools implies an exponential proliferation of ever improving constructions to interrogate the subcellular environment. A myriad of tags for labeling proteins, RNA, or DNA have arisen in the last few decades, facilitating unprecedented visualization of subcellular components and processes. Development of a broad array of modern genetically encoded sensors allows real-time, in vivo detection of molecule levels, pH, forces, enzyme activity, and othe...
Source: PLoS Genetics - March 22, 2024 Category: Genetics & Stem Cells Authors: Kelli D. Fenelon Source Type: research
