Mapping genetic effects on cell type-specific chromatin accessibility and annotating complex immune trait variants using single nucleus ATAC-seq in peripheral blood
In this study we performed single nucleus ATAC-seq (snATAC-seq) and genotyping in peripheral blood mononuclear cells from 13 individuals. Clustering chromatin accessibility profiles of 96,002 total nuclei identified 17 immune cell types and sub-types. We mapped chromatin accessibility QTLs (caQTLs) in each immune cell type and sub-type using individuals of European ancestry which identified 6,901 caQTLs at FDR (Source: PLoS Genetics)
Source: PLoS Genetics - June 8, 2023 Category: Genetics & Stem Cells Authors: Paola Benaglio Source Type: research
Spatio-temporal transcriptome dynamics coordinate rapid transition of core crop functions in ‘lactating’ pigeon
by Yujie Wang, Xun Wang, Yi Luo, Jiaman Zhang, Yu Lin, Jie Wu, Bo Zeng, Lei Liu, Peiqi Yan, Jiyuan Liang, Hongrui Guo, Long Jin, Qianzi Tang, Keren Long, Mingzhou Li
Pigeons (Columba livia) are among a select few avian species that have developed a specialized reproductive mode wherein the parents produce a ‘milk’ in their crop to feed newborn squabs. Nonetheless, the transcriptomic dynamics and role in the rapid transition of core crop functions during ‘lactation’ remain largely unexplored. Here, we generated ade novo pigeon genome assembly to construct a high resolution spatio-temporal transcriptomic landscape o...
Source: PLoS Genetics - June 8, 2023 Category: Genetics & Stem Cells Authors: Yujie Wang Source Type: research
The novel anti-phage system Shield co-opts an RmuC domain to mediate phage defense across < i > Pseudomonas < /i > species
by Elliot Macdonald, Rosanna Wright, James P. R. Connolly, Henrik Strahl, Michael Brockhurst, Stineke van Houte, Tim R. Blower, Tracy Palmer, Giuseppina Mariano
Competitive bacteria-bacteriophage interactions have resulted in the evolution of a plethora of bacterial defense systems preventing phage propagation. In recent years, computational and bioinformatic approaches have underpinned the discovery of numerous novel bacterial defense systems. Anti-phage systems are frequently encoded together in genomic loci termed defense islands. Here we report the identification and characterisation of a novel anti-phage system, that...
Source: PLoS Genetics - June 5, 2023 Category: Genetics & Stem Cells Authors: Elliot Macdonald Source Type: research
Combinations of genes at the 16p11.2 and 22q11.2 CNVs contribute to neurobehavioral traits
by Mikhail Vysotskiy, Autism Working Group of the Psychiatric Genomics Consortium , Bipolar Disorder Working Group of the Psychiatric Genomics Consortium , Schizophrenia Working Group of the Psychiatric Genomics Consortium , Lauren A. Weiss
The 16p11.2 and 22q11.2 copy number variants (CNVs) are associated with neurobehavioral traits including autism spectrum disorder (ASD), schizophrenia, bipolar disorder, obesity, and intellectual disability. Identifying specific genes contributing to each disorder and dissecting the architecture of CNV-trait association has been difficult, inspiring hypotheses of more complex models, s...
Source: PLoS Genetics - June 2, 2023 Category: Genetics & Stem Cells Authors: Mikhail Vysotskiy Source Type: research
Overlapping functions of SIX homeoproteins during embryonic myogenesis
by Maud Wurmser, Rouba Madani, Nathalie Chaverot, St éphanie Backer, Matthew Borok, Matthieu Dos Santos, Glenda Comai, Shahragim Tajbakhsh, Frédéric Relaix, Marc Santolini, Ramkumar Sambasivan, Rulang Jiang, Pascal Maire
Four SIX homeoproteins display a combinatorial expression throughout embryonic developmental myogenesis and they modulate the expression of the myogenic regulatory factors. Here, we provide a deep characterization of their role in distinct mouse developmental territories. We showed, at the hypaxial level, that theSix1:Six4 double knockout (dKO) somitic precursor cells adopt a smooth muscle fate and los...
Source: PLoS Genetics - June 2, 2023 Category: Genetics & Stem Cells Authors: Maud Wurmser Source Type: research
A polycistronic transgene design for combinatorial genetic perturbations from a single transcript in < i > Drosophila < /i >
by Alexander G. Teague, Maria Quintero, Fateme Karimi Dermani, Ross L. Cagan, Erdem Bangi
Experimental models that capture the genetic complexity of human disease and allow mechanistic explorations of the underlying cell, tissue, and organ interactions are crucial to furthering our understanding of disease biology. Such models require combinatorial manipulations of multiple genes, often in more than one tissue at once. The ability to perform complex genetic manipulationsin vivo is a key strength ofDrosophila, where many tools for sophisticated and orthogonal genetic perturbations exist. However, combining the large number...
Source: PLoS Genetics - June 2, 2023 Category: Genetics & Stem Cells Authors: Alexander G. Teague Source Type: research
The circadian clock is disrupted in pancreatic cancer
by Patrick B. Schwartz, Manabu Nukaya, Mark E. Berres, Clifford D. Rubinstein, Gang Wu, John B. Hogenesch, Christopher A. Bradfield, Sean M. Ronnekleiv-Kelly
Disruption of the circadian clock is linked to cancer development and progression. Establishing this connection has proven beneficial for understanding cancer pathogenesis, determining prognosis, and uncovering novel therapeutic targets. However, barriers to characterizing the circadian clock in human pancreas and human pancreatic cancer –one of the deadliest malignancies–have hindered an appreciation of its role in this cancer. Here, we employed normalized coeff...
Source: PLoS Genetics - June 1, 2023 Category: Genetics & Stem Cells Authors: Patrick B. Schwartz Source Type: research
Sex modifies the effect of genetic risk scores for polycystic ovary syndrome on metabolic phenotypes
by Ky ’Era V. Actkins, Genevieve Jean-Pierre, Melinda C. Aldrich, Digna R. Velez Edwards, Lea K. Davis
Females with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women, have an increased risk of developing cardiometabolic disorders such as insulin resistance, obesity, and type 2 diabetes (T2D). While only diagnosable in females, males with a family history of PCOS can also exhibit a poor cardiometabolic profile. Therefore, we aimed to elucidate the role of sex in the cardiometabolic comorbidities observed in PCOS by conducting bidirectional genetic risk score analyses in both sexes. We first co...
Source: PLoS Genetics - May 31, 2023 Category: Genetics & Stem Cells Authors: Ky ’Era V. Actkins Source Type: research
Interacting bactofilins impact cell shape of the MreB-less multicellular < i > Rhodomicrobium vannielii < /i >
by Pia Richter, Brigitte Melzer, Frank D. M üller
Most non-spherical bacteria rely on the actin-like MreB cytoskeleton to control synthesis of a cell-shaping and primarily rod-like cell wall. Diverging from simple rod shape generally requires accessory cytoskeletal elements, which locally interfere with the MreB-guided cell wall synthesis. Conserved and widespread representatives of this accessory cytoskeleton are bactofilins that polymerize into static, non-polar bundles of filaments. Intriguingly, many species of the Actinobacteria and Rhizobiales manage to grow rod-like without MreB by tip extension, yet some of them ...
Source: PLoS Genetics - May 31, 2023 Category: Genetics & Stem Cells Authors: Pia Richter Source Type: research
Evolutionary trade-off and mutational bias could favor transcriptional over translational divergence within paralog pairs
by Simon Aub é, Lou Nielly-Thibault, Christian R. Landry
How changes in the different steps of protein synthesis —transcription, translation and degradation—contribute to differences of protein abundance among genes is not fully understood. There is however accumulating evidence that transcriptional divergence might have a prominent role. Here, we show that yeast paralogous genes are more divergent in tran scription than in translation. We explore two causal mechanisms for this predominance of transcriptional divergence: an evolutionary trade-off between the precision and economy of gene expression and a larger mutat...
Source: PLoS Genetics - May 26, 2023 Category: Genetics & Stem Cells Authors: Simon Aub é Source Type: research
Hsp90 mutants with distinct defects provide novel insights into cochaperone regulation of the folding cycle
by Rebecca Mercier, Danielle Yama, Paul LaPointe, Jill L. Johnson
Molecular chaperones play a key role in maintaining proteostasis and cellular health. The abundant, essential, cytosolic Hsp90 (Heat shock protein, 90 kDa) facilitates the folding and activation of hundreds of newly synthesized or misfolded client proteins in an ATP-dependent folding pathway. In a simplified model, Hsp70 first helps load client onto Hsp90, ATP binding results in conformational changes in Hsp90 that result in the closed complex, and then less defined events result in nucleotide hydrolysis, client release and return to the open state. Cochape...
Source: PLoS Genetics - May 25, 2023 Category: Genetics & Stem Cells Authors: Rebecca Mercier Source Type: research
Canonical correlation analysis for multi-omics: Application to cross-cohort analysis
by Min-Zhi Jiang, Fran çois Aguet, Kristin Ardlie, Jiawen Chen, Elaine Cornell, Dan Cruz, Peter Durda, Stacey B. Gabriel, Robert E. Gerszten, Xiuqing Guo, Craig W. Johnson, Silva Kasela, Leslie A. Lange, Tuuli Lappalainen, Yongmei Liu, Alex P. Reiner, Josh Smith, Tamar Sofer, Kent D. Taylor, Russell P. Tracy, David J. Va nDenBerg, James G. Wilson, Stephen S. Rich, Jerome I. Rotter, Michael I. Love, Laura M. Raffield, Yun Li, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Analysis Working Group
Integrative approaches that simultaneously model multi-omics data have gained increasing popularity because...
Source: PLoS Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Min-Zhi Jiang Source Type: research
Transcriptome-wide gene-gene interaction associations elucidate pathways and functional enrichment of complex traits
by Luke M. Evans, Christopher H. Arehart, Andrew D. Grotzinger, Travis J. Mize, Maizy S. Brasher, Jerry A. Stitzel, Marissa A. Ehringer, Charles A. Hoeffer
It remains unknown to what extent gene-gene interactions contribute to complex traits. Here, we introduce a new approach using predicted gene expression to perform exhaustive transcriptome-wide interaction studies (TWISs) for multiple traits across all pairs of genes expressed in several tissue types. Using imputed transcriptomes, we simultaneously reduce the computational challenge and improve interpretability and statistical power. We discover (in the UK Biobank) and...
Source: PLoS Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Luke M. Evans Source Type: research
Functional analysis of three new alpha-thalassemia deletions involving MCS-R2 reveals the presence of an additional enhancer element in the 5 ’ boundary region
We report three novel deletions involving the Multispecies Conserved Sequences (MCS) R2, also known as the Major Regulative Element (MRE), in patients showing the α-thalassemia phenotype. The three new rearrangements showed peculiar positions of the breakpoints. 1) The (αα)ES is a telomeric 110 kb deletion ending inside the MCS-R3 element. 2) The (αα)FG, 984 bp-long, ends 51 bp upstream to MCS-R2; both are associated with a severe α-thalassemia phenotyp e. 3) The (αα)CT, 5058 bp-long starts at position +93 of MCS-R2 and is the only one associated to a mild α-thalassemia phenotype. To understand the specific role o...
Source: PLoS Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Serena Capasso Source Type: research
Taste and pheromonal inputs govern the regulation of time investment for mating by sexual experience in male < i > Drosophila melanogaster < /i >
by Seung Gee Lee, Dongyu Sun, Hongyu Miao, Zekun Wu, Changku Kang, Baraa Saad, Khoi-Nguyen Ha Nguyen, Adrian Guerra-Phalen, Dorothy Bui, Al-Hassan Abbas, Brian Trinh, Ashvent Malik, Mahdi Zeghal, Anne-Christine Auge, Md Ehteshamul Islam, Kyle Wong, Tiffany Stern, Elizabeth Lebedev, Thomas N. Sherratt, Woo Jae Kim
Males have finite resources to spend on reproduction. Thus, males rely on a ‘time investment strategy’ to maximize their reproductive success. For example, maleDrosophila melanogaster extends their mating duration when surrounded by conditions enriched with rivals. Here we report a different form of behaviora...
Source: PLoS Genetics - May 22, 2023 Category: Genetics & Stem Cells Authors: Seung Gee Lee Source Type: research
