Conserved and novel enhancers in the < i > Aedes aegypti single-minded < /i > locus recapitulate embryonic ventral midline gene expression
by Isabella Schember, William Reid, Geyenna Sterling-Lentsch, Marc S. Halfon
Transcriptionalcis-regulatory modules, e.g., enhancers, control the time and location of metazoan gene expression. While changes in enhancers can provide a powerful force for evolution, there is also significant deep conservation of enhancers for developmentally important genes, with function and sequence characteristics maintained over hundreds of millions of years of divergence. Not well understood, however, is how the overall regulatory composition of a locus evolves, with important outstanding questions such as how many enhancers are conserve...
Source: PLoS Genetics - April 29, 2024 Category: Genetics & Stem Cells Authors: Isabella Schember Source Type: research
< i > KmerAperture < /i > : Retaining < i > k < /i > -mer synteny for alignment-free extraction of core and accessory differences between bacterial genomes
by Matthew P. Moore, Mirjam Laager, Paolo Ribeca, Xavier Didelot
By decomposing genome sequences intok-mers, it is possible to estimate genome differences without alignment. Techniques such ask-mer minimisers, for example MinHash, have been developed and are often accurate approximations of distances based on fullk-mer sets. These and other alignment-free methods avoid the large temporal and computational expense of alignment. However, thesek-mer set comparisons are not entirely accurate within-species and can be completely inaccurate within-lineage. This is due, in part, to their inability to distinguish core polymorphis...
Source: PLoS Genetics - April 29, 2024 Category: Genetics & Stem Cells Authors: Matthew P. Moore Source Type: research
The impact of developmental stage, tissue type, and sex on DNA double-strand break repair in < i > Drosophila melanogaster < /i >
This study describes the impact of development, tissue-specific cycling profile, and, in some cases, sex on DSB repair outcomes, underscoring the complexity of repair in multicellular organisms. (Source: PLoS Genetics)
Source: PLoS Genetics - April 29, 2024 Category: Genetics & Stem Cells Authors: Elizabeth L. Graham Source Type: research
Deep mutational scanning of < i > Pneumocystis jirovecii < /i > dihydrofolate reductase reveals allosteric mechanism of resistance to an antifolate
by Francois D. Rouleau, Alexandre K. Dub é, Isabelle Gagnon-Arsenault, Soham Dibyachintan, Alicia Pageau, Philippe C. Després, Patrick Lagüe, Christian R. LandryPneumocystis jirovecii is a fungal pathogen that causes pneumocystis pneumonia, a disease that mainly affects immunocompromised individuals. This fungus has historically been hard to study because of our inability to grow itin vitro. One of the main drug targets inP.jirovecii is its dihydrofolate reductase (PjDHFR). Here, by using functional complementation of the baker ’s yeast ortholog, we show that PjDHFR can be inhibited by the antifolate methotrexate in a...
Source: PLoS Genetics - April 29, 2024 Category: Genetics & Stem Cells Authors: Francois D. Rouleau Source Type: research
Transcriptional control of visual neural circuit development by GS homeobox 1
by Alexandra R. Schmidt, Haiden J. Placer, Ishmael M. Muhammad, Rebekah Shephard, Regina L. Patrick, Taylor Saurborn, Eric J. Horstick, Sadie A. Bergeron
As essential components of gene expression networks, transcription factors regulate neural circuit assembly. The homeobox transcription factor encoding gene,gs homeobox 1 (gsx1), is expressed in the developing visual system; however, no studies have examined its role in visual system formation. In zebrafish, retinal ganglion cell (RGC) axons that transmit visual information to the brain terminate in ten arborization fields (AFs) in the optic tectum (TeO), pretectum (Pr),...
Source: PLoS Genetics - April 26, 2024 Category: Genetics & Stem Cells Authors: Alexandra R. Schmidt Source Type: research
Hypoxia delays steroid-induced developmental maturation in < i > Drosophila < /i > by suppressing EGF signaling
by Michael J. Turingan, Tan Li, Jenna Wright, Abhishek Sharma, Kate Ding, Shahoon Khan, Byoungchun Lee, Savraj S. Grewal
Animals often grow and develop in unpredictable environments where factors like food availability, temperature, and oxygen levels can fluctuate dramatically. To ensure proper sexual maturation into adulthood, juvenile animals need to adapt their growth and developmental rates to these fluctuating environmental conditions. Failure to do so can result in impaired maturation and incorrect body size. Here we describe a mechanism by whichDrosophila larvae adapt their development in low oxygen (hypoxia). Duri...
Source: PLoS Genetics - April 26, 2024 Category: Genetics & Stem Cells Authors: Michael J. Turingan Source Type: research
Correlation-based tests for the formal comparison of polygenic scores in multiple populations
by Sophia Gunn, Kathryn L. Lunetta
Polygenic scores (PGS) are measures of genetic risk, derived from the results of genome wide association studies (GWAS). Previous work has proposed the coefficient of determination (R2) as an appropriate measure by which to compare PGS performance in a validation dataset. Here we propose correlation-based methods for evaluating PGS performance by adapting previous work which produced a statistical framework and robust test statistics for the comparison of multiple correlation measures in multiple populations. This flexible framework can be extended to a wider variety of hypothesis tests ...
Source: PLoS Genetics - April 26, 2024 Category: Genetics & Stem Cells Authors: Sophia Gunn Source Type: research
The actin binding sites of talin have both distinct and complementary roles in cell-ECM adhesion
by Darius Camp, Bhavya Venkatesh, Veronika Solianova, Lorena Varela, Benjamin T. Goult, Guy Tanentzapf
Cell adhesion requires linkage of transmembrane receptors to the cytoskeleton through intermediary linker proteins. Integrin-based adhesion to the extracellular matrix (ECM) involves large adhesion complexes that contain multiple cytoskeletal adapters that connect to the actin cytoskeleton. Many of these adapters, including the essential cytoskeletal linker Talin, have been shown to contain multiple actin-binding sites (ABSs) within a single protein. To investigate the possible role of having such a variety of ways of li...
Source: PLoS Genetics - April 25, 2024 Category: Genetics & Stem Cells Authors: Darius Camp Source Type: research
Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli in < i > Drosophila < /i > larvae
by Kory P. Luedke, Jiro Yoshino, Chang Yin, Nan Jiang, Jessica M. Huang, Kevin Huynh, Jay Z. Parrish
An animal ’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epider mal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity ofDrosophila larvae to noxious mechanic...
Source: PLoS Genetics - April 25, 2024 Category: Genetics & Stem Cells Authors: Kory P. Luedke Source Type: research
Unraveling the genetics of arsenic toxicity with cellular morphology QTL
by Callan O ’Connor, Gregory R. Keele, Whitney Martin, Timothy Stodola, Daniel Gatti, Brian R. Hoffman, Ron Korstanje, Gary A. Churchill, Laura G. Reinholdt
The health risks that arise from environmental exposures vary widely within and across human populations, and these differences are largely determined by genetic variation and gene-by-environment (gene –environment) interactions. However, risk assessment in laboratory mice typically involves isogenic strains and therefore, does not account for these known genetic effects. In this context, genetically heterogenous cell lines from laboratory mice are promising tools...
Source: PLoS Genetics - April 25, 2024 Category: Genetics & Stem Cells Authors: Callan O ’Connor Source Type: research
Better together against genetic heterogeneity: A sex-combined joint main and interaction analysis of 290 quantitative traits in the UK Biobank
by Boxi Lin, Andrew D. Paterson, Lei Sun
Genetic effects can be sex-specific, particularly for traits such as testosterone, a sex hormone. While sex-stratified analysis provides easily interpretable sex-specific effect size estimates, the presence of sex-differences in SNP effect implies a SNP ×sex interaction. This suggests the usage of the often overlooked joint test, testing for an SNP’s main and SNP×sex interaction effects simultaneously. Notably, even without individual-level data, the joint test statistic can be derived from sex-stratified summary statistics through an omnibus m eta-analysis. Utilizing the avail...
Source: PLoS Genetics - April 24, 2024 Category: Genetics & Stem Cells Authors: Boxi Lin Source Type: research
Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages
by Liu Xu, Yibing Chen, Lingling Liu, Xinyu Hu, Chengsi He, Yuan Zhou, Xinyi Ding, Minhua Luo, Jiajing Yan, Quentin Liu, Hongsheng Li, Dongming Lai, Zhengzhi Zou
Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-B...
Source: PLoS Genetics - April 22, 2024 Category: Genetics & Stem Cells Authors: Liu Xu Source Type: research
Collider bias correction for multiple covariates in GWAS using robust multivariable Mendelian randomization
by Peiyao Wang, Zhaotong Lin, Haoran Xue, Wei Pan
Genome-wide association studies (GWAS) have identified many genetic loci associated with complex traits and diseases in the past 20 years. Multiple heritable covariates may be added into GWAS regression models to estimate direct effects of genetic variants on a focal trait, or to improve the power by accounting for environmental effects and other sources of trait variations. When one or more covariates are causally affected by both genetic variants and hidden confounders, adjusting for them in GWAS will produce biased estimation of SNP effects, known as collider bias. Seve...
Source: PLoS Genetics - April 22, 2024 Category: Genetics & Stem Cells Authors: Peiyao Wang Source Type: research
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
