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Highly Pathogenic Avian Influenza A (H5N1) Suspected in penguins and shags on the Antarctic Peninsula and West Antarctic Coast bioRxiv. Genet. Pub Date : 2024-03-18 Fabiola Leon, Celine Le Bohec, Eduardo J Pizarro, Loicka Baille, Robin Cristofari, Aymeri Houstin, Daniel P Zitterbart, Gonzalo Barriga, Elie Poulin, Juliana A Vianna
Suspected cases of Highly Pathogenic Avian Influenza (H5N1) were detected in Adelie penguins and Antarctic shags at the southernmost latitude so far in Antarctica, at two breeding sites out of 13 visited, using highly specific PCR assay. These first records mark the progression of the H5N1 panzootic into Antarctica.
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The ubiquitin ligase HUWE1 enhances WNT signaling by antagonizing destruction complex-mediated β-catenin degradation and through a mechanism independent of β-catenin stability bioRxiv. Genet. Pub Date : 2024-03-17 Joseph K McKenna, Yalan Wu, Praveen Sonkusre, Raj Chari, Andres M Lebensohn
WNT/β-catenin signaling is mediated by the transcriptional coactivator β-catenin (CTNNB1). CTNNB1 abundance is regulated by phosphorylation and proteasomal degradation promoted by a destruction complex composed of the scaffold proteins APC and AXIN1 or AXIN2, and the kinases CSNK1A1 and GSK3A or GSK3B. Loss of CSNK1A1 increases CTNNB1 abundance, resulting in hyperactive WNT signaling. Previously, we
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A novel inducible von Willebrand Factor Cre Recombinase mouse strain to study microvascular endothelial cell-specific biological processes in vivo. bioRxiv. Genet. Pub Date : 2024-03-17 Dinesh Yadav, Jeremy Conner, Yimin Wang, Thomas Saunders, Eroboghene Ubogu
Mouse models are invaluable to understanding fundamental mechanisms in vascular biology during development, in health and different disease states. Several constitutive or inducible models that selectively knockout or knock in genes in vascular endothelial cells exist; however, functional and phenotypic differences exist between microvascular and macrovascular endothelial cells in different organs
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Map of epigenetic age acceleration: a worldwide meta-analysis bioRxiv. Genet. Pub Date : 2024-03-17 Igor Yusipov, Alena Kalyakulina, Claudio Franceschi, Mikhail Ivanchenko
This study is the first systematic meta-analysis of epigenetic age acceleration of the largest publicly available DNA methylation data for healthy samples (93 datasets, 23K samples), focusing on geographic and ethnic aspects of different countries (25 countries) and populations (31 ethnicities) around the world. The most popular epigenetic tools for assessing age acceleration were examined in detail
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Neuronal CBP-1 is required for enhanced body muscle proteostasis in response to reduced translation downstream of mTOR bioRxiv. Genet. Pub Date : 2024-03-17 Santina Snow, Dilawar Mir, Zhengxin Ma, Jordan Horrocks, Matthew Cox, Marissa Ruzga, Hussein Sayed, Aric N Rogers
Background: The ability to maintain muscle function decreases with age and loss of proteostatic function. Diet, drugs, and genetic interventions that restrict nutrients or nutrient signaling help preserve long-term muscle function and slow age-related decline. Previously, it was shown that attenuating protein synthesis downstream of the mechanistic target of rapamycin (mTOR) gradually increases expression
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Loss of the Na+/K+ cation pump CATP-1 suppresses nekl-associated molting defects bioRxiv. Genet. Pub Date : 2024-03-17 David S. Fay, Shaonil Binti, Phillip T Edeen
The conserved C. elegans protein kinases NEKL-2 and NEKL-3 regulate multiple steps of membrane trafficking and are required for larval molting. Through a forward genetic screen we identified a loss-of-function mutation in catp-1 as a suppressor of molting defects in synthetically lethal nekl-2; nekl-3 double mutants. catp-1 is predicted to encode a membrane-associated P4-type ATPase involved in Na+K+
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Analyzing bivariate cross-trait genetic architecture in GWAS summary statistics with the BIGA cloud computing platform bioRxiv. Genet. Pub Date : 2024-03-16 Yujue Li, Fei Xue, Bingxuan Li, Yilin Yang, Zirui Fan, Juan Shu, Xiaochen Yang, Xiyao Wang, Jinjie Lin, Carlos Copana, Bingxin Zhao
As large-scale biobanks provide increasing access to deep phenotyping and genomic data, genome-wide association studies (GWAS) are rapidly uncovering the genetic architecture behind various complex traits and diseases. GWAS publications typically make their summary-level data (GWAS summary statistics) publicly available, enabling further exploration of genetic overlaps between phenotypes gathered from
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Robust and Accurate Bayesian Inference of Genome-Wide Genealogies for Large Samples bioRxiv. Genet. Pub Date : 2024-03-16 Yun Deng, Rasmus Nielsen, Yun S. Song
The Ancestral Recombination Graph (ARG), which describes the full genealogical history of a sample of genomes, is a vital tool in population genomics and biomedical research. Recent advancements have increased ARG reconstruction scalability to tens or hundreds of thousands of genomes, but these methods rely on heuristics, which can reduce accuracy, particularly in the presence of model misspecification
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Post-GWAS functional analyses of CNTNAP5 suggests its role in glaucomatous neurodegeneration bioRxiv. Genet. Pub Date : 2024-03-16 Sudipta Chakraborty, Jyotishman Sarma, Shantanu Saha Roy, Sukanya Mitra, Sayani Bagchi, Sankhadip Das, Sreemoyee Saha, Surajit Mahapatra, Samsiddhi Bhattacharjee, Mahua Maulik, Moulinath Acharya
Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based GWAS, we identified a novel CNTNAP5 genic region, significantly associated with PACG. In the current study, we have extended our perception of CNTNAP5 involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating
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Replication protein-A, RPA, plays a pivotal role in the maintenance of recombination checkpoint in yeast meiosis bioRxiv. Genet. Pub Date : 2024-03-16 Arivarasan Sampathkumar, Zhong Chen, Yuting Tang, Yurika Fujita, Masaru Ito, Akira Shinohara
DNA double-strand breaks (DSBs) activate DNA damage responses (DDR) in both mitotic and meiotic cells. A single-stranded DNA (ssDNA) binding protein, Replication protein-A (RPA) binds to the ssDNA formed at DSBs to activate ATR/Mec1 kinase for the response. Meiotic DSBs induce homologous recombination monitored by a meiotic DDR called the recombination checkpoint that blocks the pachytene exit in meiotic
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Identification of candidate causal cis-regulatory variants underlying electrocardiographic QT interval GWAS loci bioRxiv. Genet. Pub Date : 2024-03-15 Ashish Kapoor
Identifying causal variants among tens or hundreds of associated variants at each locus mapped by genome-wide association studies (GWAS) of complex traits is a challenge. As vast majority of GWAS variants are noncoding, sequence variation at cis-regulatory elements affecting transcriptional expression of specific genes is a widely accepted molecular hypothesis. Following this cis-regulatory hypothesis
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Insights Into Ribosomal DNA (rDNA) Dominance and Magnification Through Characterization of Isogenic Deletion Alleles bioRxiv. Genet. Pub Date : 2024-03-15 Selina M Kindelay, Keith A. Maggert
The major loci for the large primary ribosomal RNA genes (35S rRNAs) exist as hundreds to thousands of tandem repeats in all organisms, and dozens to hundreds in Drosophila. The highly repetitive nature of the rDNA makes it intrinsically unstable, and many conditions arise from the reduction or magnification of copy number, but the conditions under which it does so remains unknown. By targeted DNA
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A conserved protein tyrosine phosphatase, PTPN-22, functions in diverse developmental processes in C. elegans bioRxiv. Genet. Pub Date : 2024-03-15 Shaonil Binti, Adison G Linder, Philip T Edeen, David S. Fay
Protein tyrosine phosphatases non-receptor type (PTPNs) have been studied extensively in the context of the adaptive immune system; however, their roles beyond immunoregulation are less well explored. Here we identify novel functions for the conserved C. elegans phosphatase PTPN-22, establishing its role in nematode molting, cell adhesion, and cytoskeletal regulation. Through a non-biased genetic screen
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Meiosis-specific functions of kinetochore protein SPC105R required for chromosome segregation in Drosophila oocytes bioRxiv. Genet. Pub Date : 2024-03-14 Jay N Joshi, Neha Changela, Lia Mahal, Tyler Defosse, Janet K McKim, Lin-Ing Wang, Arunika Das, Joanatta G Shapiro, Kim McKim
The reductional division of meiosis I requires the separation of chromosome pairs towards opposite poles. We have previously implicated the outer kinetochore protein SPC105R/KNL1 in driving meiosis I chromosome segregation through lateral attachments to microtubules and co-orientation of sister centromeres. To identify the domains of SPC105R that are critical for meiotic chromosome segregation, an
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A CLASP1 variant suggests a phenotypic relation with lissencephaly in humans bioRxiv. Genet. Pub Date : 2024-03-14 RAWAN ALSAFH, AMAL ALHASHEM, ALY ELSAYED, ZAFER YUEKSEL, KALTHOUM GRAIES-TLILI, FARAH THABET, BRAHIM TABARKI
Lissencephaly is a severe brain developmental disorder; characterized by reduced brain folding due to defective neuronal migration. This study investigates the genetic basis of lissencephaly in a consanguineous family, focusing on the CLASP1 gene. Whole-exome sequencing identified a novel homozygous variant (c.4442G>A p.(Arg1481His)) in CLASP1. Clinical evaluation revealed severe developmental delays
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metaGWASmanager: A toolbox for an automated workflow from phenotypes to meta-analysis in GWAS consortia bioRxiv. Genet. Pub Date : 2024-03-14 Zulema Rodriguez-Hernandez, Mathias Gorski, Maria Tellez Plaza, Pascal Schlosser, Matthias Wuttke
Summary: This paper introduces the metaGWASmanager, which streamlines genome-wide association studies within large-scale meta-analysis consortia. It is a toolbox for both the central consortium analysis group and participating studies to generate homogeneous phenotypes, minimize variance from inconsistent methodologies, ensure high-quality association results, and implement time-efficient quality control
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Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts bioRxiv. Genet. Pub Date : 2024-03-14 Xiaohui Lin, Dipika Gupta, Alina Vaitsiankova, Seema Khattri Bhandari, Kay Sze Karina Leung, Demis Menolfi, Brian J Lee, Helen R Russell, Steven Gershik, Wei Gu, Peter J McKinnon, Francoise DANTZER, Eli Rothenberg, Alan E Tomkinson, Shan Zha
PARP1&2 enzymatic inhibitors (PARPi) are promising cancer treatments. But recently, their use has been hindered by unexplained severe anemia and treatment-related leukemia. In addition to enzymatic inhibition, PARPi also trap PARP1&2 at DNA lesions. Here, we report that unlike Parp2-/- mice, which develop normally, mice expressing catalytically-inactive Parp2 (E534A, Parp2EA/EA) succumb to Tp53- and
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Discovery of knock-down resistance in the major malaria vector Anopheles funestus reveals the legacy of persistent DDT pollution. bioRxiv. Genet. Pub Date : 2024-03-14 Joel Odero, Tristan PW Dennis, Brian Polo, Joachim Nwezeobi, Marilou Bodde, Sanjay Curtis Nagi, Anastasia Hernandez-Koutoucheva, Ismail H Nambunga, Hamis Bwanary, Gustav Mkandawile, Nicodem James Govella, Emmanuel W. Kaindoa, Heather M. Ferguson, Eric Ochomo, Chris S Clarkson, Alistair Miles Miles, Mara K.N Lawniczak, David Weetman, Francesco Baldini, Fredros O Okumu
A major mechanism of insecticide resistance in arthropod pests is knock-down resistance (kdr) caused by mutations in the voltage-gated sodium channel (Vgsc) gene. Common in most malaria Anopheles vector species, kdr mutations have never been observed in Anopheles funestus, the principal vector in Eastern and Southern Africa. From whole-genome sequencing of 333 An. funestus samples from a breadth of
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Functional characterization of QT interval associated SCN5A enhancer variants identify combined additive effects bioRxiv. Genet. Pub Date : 2024-03-14 Ashish Kapoor
Several empirical and theoretical studies suggest presence of multiple enhancers per gene that collectively regulate gene expression, and that common sequence variation impacting on the activities of these enhancers is a major source of inter-individual variability in gene expression. However, for vast majority of genes, enhancers and the underlying regulatory variation remains unknown. Even for the
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Multi-modal comparison of molecular programs driving nurse cell death and clearance in Drosophila melanogaster oogenesis bioRxiv. Genet. Pub Date : 2024-03-14 Shruthi Bandyadka, Diane PV Lebo, Albert Mondragon, Sandy B Serizier, Julian Kwan, Jeanne S Peterson, Alexandra Y Chasse, Victoria Jenkins, Anoush Calikyan, Anthony Ortega, Joshua D Campbell, Andrew Emili, Kimberly McCall
The death and clearance of nurse cells is a consequential milestone in Drosophila melanogaster oogenesis. In preparation for oviposition, the germline-derived nurse cells bequeath to the developing oocyte all their cytoplasmic contents and undergo programmed cell death. The death of the nurse cells is controlled non-autonomously and is precipitated by epithelial follicle cells of somatic origin acquiring
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Aberrant homeodomain-DNA cooperative dimerization underlies distinct developmental defects in two dominant CRX retinopathy models bioRxiv. Genet. Pub Date : 2024-03-14 Yiqiao Zheng, Gary D Stormo, Shiming Chen
Paired-class homeodomain transcription factors (HD TFs) play essential roles in vertebrate development, and their mutations are linked to human diseases. One unique feature of paired-class HD is cooperative dimerization on specific palindrome DNA sequences. Yet, the functional significance of HD cooperative dimerization in animal development and its dysregulation in diseases remain elusive. Using the
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DNA replication initiation drives focal mutagenesis and rearrangements in human cancers bioRxiv. Genet. Pub Date : 2024-03-14 Pierre Murat, Guillaume Guilbaud, Julian E Sale
The rate and pattern of mutagenesis in cancer genomes is significantly influenced by DNA accessibility and active biological processes. Here we show that efficient sites of replication initiation drive and modulate specific mutational processes in cancer. Sites of replication initiation impede nucleotide excision repair in melanoma and are off-targets for activation-induced deaminase (AICDA) activity
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Steppe Ancestry in western Eurasia and the spread of the Germanic Languages bioRxiv. Genet. Pub Date : 2024-03-14 Hugh McColl, Guus Kroonen, J. Victor Moreno-Mayar, Frederik Valeur Seersholm, Gabriele Scorrano, Thomaz Pinotti, Tharsika Vimala, Soren M. Sindbaek, Per Ethelberg, Ralph Fyfe, Marie-Jose Gaillard, Hanne M. Ellegard Larsen, Morten Fischer Mortensen, Fabrice Demeter, Marie Louise S. Jorkov, Sophie Bergerbrant, Peter de Barros Damgaard, Morten E. Allentoft, Lasse Vinner, Charleen Gaunitz, Abigail Ramsoe
Germanic-speaking populations historically form an integral component of the North and Northwest European cultural configuration. According to linguistic consensus, the common ancestor of the Germanic languages, which include German, English, Frisian, Dutch as well as the Nordic languages, was spoken in Northern Europe during the Pre-Roman Iron Age. However, important questions remain concerning the
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Estimating evolutionary and demographic parameters via ARG-derived IBD bioRxiv. Genet. Pub Date : 2024-03-13 Zhendong Huang, Jerome Kelleher, Yao-ban Chan, David Balding
Inference of demographic and evolutionary parameters from a sample of genome sequences often proceeds by first inferring identical-by-descent (IBD) genome segments. By exploiting efficient data encoding based on the ancestral recombination graph (ARG), we obtain three major advantages over current approaches: (i) no need to impose a length threshold on IBD segments, (ii) IBD can be defined without
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Genotype prediction of 336,463 samples from public expression data bioRxiv. Genet. Pub Date : 2024-03-13 Afrooz Razi, Christopher C Lo, Sirou Wang, Jeffrey T Leek, Kasper D Hansen
Tens of thousands of RNA-sequencing experiments comprising hundreds of thousands of individual samples have now been performed. These data represent a broad range of experimental conditions, sequencing technologies, and hypotheses under study. The Recount project has aggregated and uniformly processed hundreds of thousands of publicly available RNA-seq samples. Most of these samples only include RNA
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A novel regulatory pathway recognizes and degrades transcripts with long 3′ untranslated regions bioRxiv. Genet. Pub Date : 2024-03-13 Ciarán W.P. Daly, Katla Kristjánsdóttir, Jessica D. West, Luyen Tien Vu, Elizabeth A. Fogarty, Rene Geissler, Ciara McDermott, Akila Venkataramany, Andrew Grimson
Quantitative control of gene expression is fundamental to cellular function, and post transcriptional regulation is a consequential, additional layer of control over protein output. Within mammalian mRNAs, the 3′ untranslated region (3′UTR) acts as a hub of regulatory control, typically mediated by regulatory sequence elements within the 3′UTR. We have found that expression from transcripts with long
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Multiomics Analysis Reveals Extensive Remodeling of the Extracellular Matrix and Cellular Metabolism Due to Plakophilin-2 Knockdown in Guinea Pigs bioRxiv. Genet. Pub Date : 2024-03-13 Rui Song, Haiyan Wu, Lihui Yu, Jingning Yu, Wenhui yang, Wenjun Wu, Fei Sun, Haizhen Wang
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death (SCD) in young individuals, yet the mechanisms underlying its pathogenesis, particularly the role of plakophilin-2 (PKP2), remain incompletely understood. This study aimed to elucidate the profile of molecular and metabolic consequences of PKP2 knockdown in a guinea pig model of ARVC. We employed adeno-associated
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Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models bioRxiv. Genet. Pub Date : 2024-03-13 Ye-Jin Park, Tzu-Chiao Lu, Tyler Jackson, Lindsey D. Goodman, Lindsey Ran, Jiaye Chen, Chung-Yi Liang, Erin Harrison, Christina Ko, Ao-Lin Hsu, Shinya Yamamoto, Yanyan Qi, Hugo J. Bellen, Hongjie Li
Peripheral tissues become disrupted in Alzheimer's Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aβ42 and Tau, in neurons impacts the periphery is lacking. Using Drosophila, a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer's Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes
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Independent expansion, selection and hypervariability of the TBC1D3 gene family in humans bioRxiv. Genet. Pub Date : 2024-03-13 Evan Eichler, Xavi Guitart, David Porubsky, DongAhn Yoo, Max L. Dougherty, Philip C Dishuck, Katherine M. Munson, Alexandra P. Lewis, Kendra Hoekzema, Jordan Knuth, Stephen Chang, Tomi Pastinen
TBC1D3 is a primate-specific gene family that has expanded in the human lineage and has been implicated in neuronal progenitor proliferation and expansion of the frontal cortex. The gene family and its expression have been challenging to investigate because it is embedded in high identity and highly variable segmental duplications. We sequenced and assembled the gene family using long-read sequencing
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Differential selective regimes identify categories of transposable elements with regulatory function bioRxiv. Genet. Pub Date : 2024-03-13 Yari Cerruti, Daniela Fusco, Mahdis Jahanbin, Davide Marnetto, Paolo Provero
Transposable elements (TEs) are powerful drivers of genome evolution, in part through their ability to rapidly rewire the host regulatory network by creating transcription factor binding sites that can potentially be turned to the host's advantage in a process called exaptation. We use methods of comparative genomics and population genetics to identify the TE categories that have most contributed to
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A genome-wide association study implicates the olfactory system in Drosophila melanogaster diapause-associated lifespan extension and fecundity bioRxiv. Genet. Pub Date : 2024-03-12 Sreesankar Easwaran, Denise Montell
The effects of environmental stress on animal life are gaining importance with climate change. Diapause is a dormancy program that occurs in response to an adverse environment, followed by resumption of development and reproduction upon the return of favorable conditions. Diapause is a complex trait, so we leveraged the Drosophila genetic reference panel (DGRP) lines and conducted a Genome-Wide Association
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Analysis of meiotic recombination in Drosophila simulans shows heterozygous inversions do not cause an interchromosomal effect bioRxiv. Genet. Pub Date : 2024-03-12 Bowen Man, Elizabeth Kim, Alekhya Vadlakonda, David L Stern, Nicole Crown
Chromosome inversions are of unique importance in the evolution of genomes and species because when heterozygous with a standard arrangement chromosome, they suppress meiotic crossovers within the inversion. In Drosophila species, heterozygous inversions also cause the interchromosomal effect, whereby the presence of a heterozygous inversion induces a dramatic increase in crossover frequencies in the
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A genetic perspective on the recent demographic history of Ireland and Britain bioRxiv. Genet. Pub Date : 2024-03-12 Ashwini Shanmugam, Michael Merrigan, Seamus O'Reilly, Anne M Molloy, Lawrence Brody, Orla Hardiman, Russell L McLaughlin, Gianpiero L Cavalleri, Ross P. Byrne, Edmund H Gilbert
Background: While subtle yet discrete clusters of genetic identity across Ireland and Britain have been identified, their demographic history is unclear. Methods: Using genotype data from 6,574 individuals with associated regional Irish or British ancestry, we identified Irish-like and British-like genetic communities using network community detection. We segregated Identity-by-Descent (IBD) and Runs-of-Homozygosity
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Putative Looping Factor ZNF143/ZFP143 is an Essential Transcriptional Regulator with No Looping Function bioRxiv. Genet. Pub Date : 2024-03-12 Domenic N Narducci, Anders S Hansen
Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc finger transcription factor ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143's
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Loss of Bbs8 leads to cystic kidney disease in mice and affects tubulin acetylation through HDAC2 bioRxiv. Genet. Pub Date : 2024-03-12 Emilia Kieckhoefer, Peter A. Matthiessen, Lena K. Ebert, Christina Klausen, Dagmar Wachten, Thomas Benzing, Helen Louise May-Simera, Bernhard Schermer
Bardet-Biedl Syndrome (BBS) is a genetic disorder marked by considerable genetic and phenotypic diversity. BBS often presents as a combination of retinitis pigmentosa, obesity, polydactyly, and cystic kidney disease and is considered a model ciliopathy. The syndrome is caused by pathogenic variants in BBS genes, some of which encode components of a ciliary multi-protein complex, known as the BBSome
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IQCH regulates spermatogenesis by interacting with CaM to promote the expression of RNA-binding proteins bioRxiv. Genet. Pub Date : 2024-03-12 Tiechao Ruan, Ruixi Zhou, Yihong Yang, Junchen Guo, Chuan Jiang, Xiang Wang, Gan Shen, Siyu Dai, Suren Chen, Ying Shen
IQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H (IQCH) in a Chinese family with male infertility characterized by a cracked flagellar axoneme and abnormal
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Tbx1 haploinsufficiency causes brain metabolic and behavioral anomalies in adult mice which are corrected by vitamin B12 treatment bioRxiv. Genet. Pub Date : 2024-03-12 Marianna Caterino, Debora Paris, Giulia Torromino, Michele Costanzo, Gemma Flore, Annabella Tramice, Elisabetta Golini, Silvia Mandillo, Diletta Cavezza, Claudia Angelini, Margherita Ruoppolo, Andrea Motta, Elvira De Leonibus, Antonio Baldini, Elizabeth Illingworth, Gabriella Lania
Introduction The brain-related phenotypes observed in 22q11.2 deletion syndrome (22q11.2DS) are highly variable and their origin is poorly understood. Changes in brain metabolism may cause or contribute to the phenotypes, given that many of the deleted genes (approx. 10%) are implicated in metabolic processes, but this is currently unknown. It is clearly important to address this knowledge gap, but
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MegaLMM improves genomic predictions in new environments using environmental covariates bioRxiv. Genet. Pub Date : 2024-03-11 Haixiao Hu, Renaud Rincent, Daniel E. Runcie
Multi-environment trials (METs) are crucial for identifying varieties that perform well across a target population of environments (TPE). However, METs are typically too small to sufficiently represent all relevant environment-types, and face challenges from changing environment-types due to climate change. Statistical methods that enable prediction of variety performance for new environments beyond
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A Drosophila model to screen Alport syndrome COL4A5 variants for their functional pathogenicity bioRxiv. Genet. Pub Date : 2024-03-11 Jianli Duan, Pei Wen, Yunpo Zhao, Joyce van de Leemput, Jennifer Lai, Damian Fermin, Bradley A Warady, Susan L Furth, Derek K Ng, Matthew Sampson, Zhe Han
Alport syndrome is a hereditary chronic kidney disease, attributed to rare pathogenic variants in either of three collagen genes (COL4A3/4/5) with most localized in COL4A5. Trimeric type IV Collagen α3α4α5 is essential for the glomerular basement membrane that forms the kidney filtration barrier. A means to functionally assess the many candidate variants and determine pathogenicity is urgently needed
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Interleaved intersectional strategy enables genetic lineage tracing with enhanced specificity bioRxiv. Genet. Pub Date : 2024-03-11 maoying han, zhicong liu, xiuzhen huang, lei liu, bo zhou, Kathy Lui, qiang shu, Bin Zhou
Dual recombinases have been increasingly employed for enhanced precision in genetic targeting. Recent studies utilizing an intersectional genetic approach have revealed that fibroblasts derived from the endocardium (EndoFb) play a pivotal role in cardiac fibrosis. However, this strategy faces limitations primarily due to the potential ectopic genetic labeling by the constitutive Dre recombinase, especially
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The effect of altitude on the expression of immune-related genes in Peruvian rural indigenous bioRxiv. Genet. Pub Date : 2024-03-11 Luis Jaramillo-Valverde, Gilderlanio Santana de Araújo, Julio A. Poterico, Catalina Martinez-Jaramillo, Vicky Roa-Linares, Sandra Alvites-Arrieta, Nelis Pablo-Ramirez, Milward Ubillus, Diana Palma-Lozano, Carolina Silva-Carvalho, Luca Vasconcelos-da-Gama, Lucas F Costa, Eduardo Tarazona-Santos, Soumya Raychaudhuri, Heinner Guio
Background: Some genes associated with immune response have been elucidated in some Andean populations, which may explain part of the immune system adaptation and pathogen response in high-altitude residents. We performed differential expression analysis and mainly focused on genes with high fold-change between groups and those genes with differential expression related to the immune system. Methods:
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A Scalable Adaptive Quadratic Kernel Method for Interpretable Epistasis Analysis in Complex Traits bioRxiv. Genet. Pub Date : 2024-03-11 Boyang Fu, Prateek Anand, Aakarsh Anand, Joel Mefford, Sriram Sankararaman
Our knowledge of the contribution of genetic interactions (epistasis) to variation in human complex traits remains limited, partly due to the lack of efficient, powerful, and interpretable algorithms to detect interactions. Recently proposed approaches for set-based association tests show promise in improving power to detect epistasis by examining the aggregated effects of multiple variants. Nevertheless
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Variation and interaction of distinct subgenomes contribute to growth diversity in intergeneric hybrid fish bioRxiv. Genet. Pub Date : 2024-03-10 Li Ren, Mengxue Luo, Jialin Cui, Xin Gao, Hong Zhang, Ping Wu, Zehong Wei, Yakui Tai, Mengdan Li, Kaikun Luo, Shaojun Liu
Intergeneric hybridization greatly reshapes regulatory interactions among allelic and non-allelic genes. However, their effects on growth diversity remain poorly understood in animals. In this study, we conducted whole-genome sequencing and mRNA-seq analyses in diverse hybrid varieties resulting from the intergeneric hybridization of goldfish (Carassius auratus red var.) and common carp (Cyprinus carpio)
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Impaired central pattern generators due to abnormal EPHA4 signaling leads to idiopathic scoliosis bioRxiv. Genet. Pub Date : 2024-03-10 Lianlei Wang, Sen Zhao, Xinyu Yang, Pengfei Zheng, Wen Wen, Kexin Xu, Xi Cheng, Qing Li, Anas M. Khanshour, Yoshinao Koike, Junjun Liu, Xin Fan, Nao Otomo, Zefu Chen, Yaqi Li, Lulu Li, Haibo Xie, Panpan Zhu, Xiaoxin Li, Yuchen Niu, Shengru Wang, Sen Liu, Suomao Yuan, Chikashi Terao, Ziquan Li, Shaoke Chen, Xiuli Zhao, Pengfei Liu, Jennifer E Posey, Zhihong Wu, Guixing Qiu, Shiro Ikegawa, James Lupski
Idiopathic scoliosis (IS) is the most common form of spinal deformity with unclear pathogenesis. In this study, we firstly reanalyzed the loci associated with IS, drawing upon previous studies. Subsequently, we mapped these loci to candidate genes using either location-based or function-based strategies. To further substantiate our findings, we verified the enrichment of variants within these candidate
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Species-specific variation in mitochondrial genome tandem repeat polymorphisms in hares (Lepus spp., Lagomorpha, Leporidae) provides insight into their evolution bioRxiv. Genet. Pub Date : 2024-03-09 Riikka Tapanainen, Koit Aasumets, Zsofia Fekete, Steffi Goffart, Eric Dufour, Jaakko L. O. Pohjoismaki
The non-coding regions of the mitochondrial DNAs (mtDNAs) of hares, rabbits, and pika (Lagomorpha) contain short (~20 bp) and long (130-160 bp) tandem repeats, absent in related mammalian orders. In the presented study, we provide functional annotation for mountain hare (Lepus timidus) and brown hare (L. europaeus) mtDNA non-coding regions, together with a species- and population-level analysis of
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Exploring the mitochondrial genomes and phylogenetic relationships of eleven Bryconidae species bioRxiv. Genet. Pub Date : 2024-03-09 Edna Judith Marquez, Daniel Alfredo Gomez-Chavarria, Juan Fernando Alzate
Comparative mitogenomics and its evolutionary relationships within Bryconidae remains largely unexplored. To bridge this gap, this study assembled 15 mitogenomes from 11 Bryconidae species, including five newly sequenced. Salminus mitogenomes, exceeding 17,700 bp, exhibited the largest size, contrasting with a median size of 16,848 bp in the remaining species (Brycon and Chilobrycon). These mitogenomes
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ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis bioRxiv. Genet. Pub Date : 2024-03-09 Kathryn M Yammine, Sophia Mirda Abularach, Seo-yeon Kim, Agata A Bikovtseva, Jinia Lilianty, Vincent L Butty, Richard P Schiavoni, John F Bateman, Shireen R Lamandé, Matthew D Shoulders
Collagenopathies are a group of clinically diverse disorders caused by defects in collagen folding and secretion. For example, mutations in the gene encoding collagen type-II, the primary collagen in cartilage, can lead to diverse chondrodysplasias. One example is the Gly1170Ser substitution in procollagen-II, which causes precocious osteoarthritis. Here, we biochemically and mechanistically characterize
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Mono-methylated histones control PARP-1 in chromatin and transcription bioRxiv. Genet. Pub Date : 2024-03-09 Gbolahan G Bamgbose, Guillaume Bordet, Niraj Lodhi, Alexei Tulin
PARP-1 is central to transcriptional regulation under both normal and stress conditions, with the governing mechanisms yet to be fully understood. Our biochemical and ChIP-seq-based analyses showed that PARP-1 binds specifically to active histone marks, particularly H4K20me1. We found that H4K20me1 plays a critical role in facilitating PARP-1 binding and the regulation of PARP-1-depenednt loci during
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Rapid Degradation of the Human ACE2 Receptor Upon Binding and Internalization of SARS-Cov-2-Spike-RBD Protein bioRxiv. Genet. Pub Date : 2024-03-08 Paul Feinstein
It is widely accepted that the SARS-CoV-2 betacoronavirus infects humans through binding the human Angiotensin Receptor 2 (ACE2) that lines the nasal cavity and lungs, followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) cofactor. ACE2 binding is mediated by an approximately 200-residue portion of the SARS-CoV-2 extracellular spike protein, the receptor binding domain
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Coronavirus Spike-RBD Variants Differentially Bind to the Human ACE2 Receptor bioRxiv. Genet. Pub Date : 2024-03-08 Paul Feinstein
The SARS-CoV-2 betacoronavirus infects people through binding the human Angiotensin Receptor 2 (ACE2), followed by import into a cell utilizing the Transmembrane Protease, Serine 2 (TMPRSS2) and Furin cofactors. Analysis of the SARS-CoV-2 extracellular spike protein has suggested critical amino acids necessary for binding within a 197-residue portion, the receptor binding domain (RBD). A cell-based
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Sensing of dietary amino acids and regulation of calcium dynamics in adipose tissues through Adipokinetic hormone in Drosophila bioRxiv. Genet. Pub Date : 2024-03-08 Muhammad Ahmad, Shang Wu, Xuan Guo, Norbert Perrimon, Li He
Nutrient sensing and the subsequent metabolic responses are fundamental functions of animals, closely linked to diseases such as type 2 diabetes and various obesity-related diseases. Drosophila melanogaster has emerged as an excellent model for investigating metabolism and its associated disorders. In this study, we used live-cell imaging to demonstrate that the fly functional homolog of mammalian
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Exploration of a European-centered strawberry diversity panel provides markers and candidate genes for the control of fruit quality traits bioRxiv. Genet. Pub Date : 2024-03-08 Alexandre Prohaska, Pol Rey-Serra, Johann Petit, Aurelie Petit, Justine Petit, Christophe Rothan, Beatrice Denoyes
Fruit quality traits are major breeding targets in cultivated strawberry (Fragaria x ananassa). Taking into account the requirements of both growers and consumers when selecting high quality cultivars is a real challenge. Here, we used an original diversity panel enriched with unique European accessions and the 50K FanaSNP array to highlight the evolution of strawberry diversity over the past 160 years
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Targeted Long-Read Bisulfite Sequencing for Promoter Methylation Analysis in Severe Preterm Birth bioRxiv. Genet. Pub Date : 2024-03-08 Silvana Pereyra, Angela Sardina, Rita Neumann, Celia May, Rossana Sapiro, Bernardo Bertoni, Mónica Cappetta
DNA methylation plays a critical role in the dynamics of gene expression regulation and the development of various disorders. Whole-genome bisulfite sequencing can provide single base resolution of CpG methylation levels and is the "gold standard" for DNA methylation quantification, but it also has a high cost. In contrast, targeted sequencing is optimal when focusing on specific candidate regions
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DNA binding site II is required for RAD51 recombinogenic activity in Arabidopsis thaliana bioRxiv. Genet. Pub Date : 2024-03-08 Valentine Petiot, Charles I White, Olivier Da Ines
Homologous recombination is a major pathway for the repair of DNA double strand breaks, essential both to maintain genomic integrity and to generate genetic diversity. Mechanistically, homologous recombination involves the use of a homologous DNA molecule as a template to repair the break. In eukaryotes, the search for and invasion of the homologous DNA molecule is carried out by two recombinases,
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Adaptive admixture at ACKR1 (the Duffy locus) may have shaped Plasmodium vivax prevalence in Oman bioRxiv. Genet. Pub Date : 2024-03-07 Paige E. Haffener, Arwa Z. Al-Riyami, Shoaib Al-Zadjali, George B.J. Busby, Sulaiman Al Mahdhuri, Mohammed Al-Rawahi, Saif Al Hosni, Ali Al Marhoobi, Ammar Al Sheriyani, Ellen M. Leffler
Malaria in humans is largely caused by two divergent species of Plasmodium parasites, P. vivax and P. falciparum, both of which have driven the spread of protective alleles in human populations. Notably, an erythrocyte-specific Duffy null allele (FyES) confers resistance to P. vivax malaria and has been identified as a target of strong, recent positive selection in multiple African admixed populations
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Antisense transcription can induce expression memory via stable promoter repression bioRxiv. Genet. Pub Date : 2024-03-07 Verena Mutzel, Till Schwämmle, Svearike Oeverdieck, Lucija Librenjak, Benedikt Boesen, Melissa Bothe, Rutger AF Gjaltema, Ilona Dunkel, Gemma Noviello, Edda G Schulz
The capacity of cells to retain a memory of previous signals enables them to adopt unique cell fates and adjust to their surrounding environment. The underlying gene expression memory can arise from mutual repression of two genes, forming a toggle switch. Such mutual repression may occur at antisense loci, where two convergently oriented genes repress each other in cis. Under which conditions antisense
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Proteogenomic analysis reveals adaptive strategies to alleviate the consequences of aneuploidy in cancer bioRxiv. Genet. Pub Date : 2024-03-07 Jan-Eric Boekenkamp, Kristina Keuper, Stefan Redel, Karen Barthel, Leah Johnson, Angela Wieland, Markus Raschle, Zuzana Storchova
Aneuploidy is prevalent in cancer and associates with fitness advantage and poor patient prognosis. Yet, experimentally induced aneuploidy initially leads to adverse effects and impaired proliferation, suggesting that cancer cells must adapt to aneuploidy. We performed in vitro evolution of cells with extra chromosomes and obtained cell lines with improved proliferation and gene expression changes
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RPA and Rad27 limit templated and inverted insertions at DNA breaks bioRxiv. Genet. Pub Date : 2024-03-07 Grzegorz Ira, Yang Yu, Kaifu Chen, Xin Wang, Jordan Fox, Philip John Hastings, Yang Yu, Qian Li
Formation of templated insertions at DNA double-strand breaks (DSBs) is very common in cancer cells. The mechanisms and enzymes regulating these events are largely unknown. Here, we investigated templated insertions in yeast at DSBs using amplicon sequencing across a repaired locus. We document very short (most ~5-34 bp), templated inverted duplications at DSBs. They are generated through a foldback
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Impacts of yeast Tma20/MCTS1, Tma22/DENR and Tma64/eIF2D on translation reinitiation and ribosome recycling bioRxiv. Genet. Pub Date : 2024-03-07 Kristina Jendruchov, Swati Gaikwad, Kristyna Poncova, Stanislava Gunisova, Leos Shivaya Valasek, Alan G. Hinnebusch
Recycling of 40S ribosomal subunits following translation termination, entailing release of deacylated tRNA and dissociation of the empty 40S subunit from mRNA, involves yeast Tma20/Tma22 heterodimer and Tma64, counterparts of mammalian MCTS1/DENR and eIF2D. MCTS1/DENR enhance reinitiation at short upstream open reading frames (uORFs) harboring penultimate codons that confer dependence on these factors
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Simultaneous Inference of Past Demography and Selection from the Ancestral Recombination Graph under the Beta Coalescent bioRxiv. Genet. Pub Date : 2024-03-07 Kevin Korfmann, Thibaut Paul Patrick Sellinger, Fabian Freund, Matteo Fumagalli, Aurelien Tellier
The reproductive mechanism of a species is a key driver of genome evolution. The standard Wright-Fisher model for the reproduction of individuals in a population assumes that each individual produces a number of offspring negligible compared to the total population size. Yet many species of plants, invertebrates, prokaryotes or fish exhibit neutrally skewed offspring distribution or strong selection