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G3: Genes—Genomes—Genetics

Yunlong Ma, Saixian Zhang, Kaili Zhang, Chengchi Fang, Shengsong Xie, Xiaoyong Du, Xinyun Li, Debin Ni, Shuhong Zhao
Identifying genetic basis of domestication and improvement in livestock contributes to our understanding of the role of artificial selection in genome shaping. Here we used whole-genome sequencing and the genotyping by sequencing approach to detect artificial selection signatures and identify the associated SNPs of two economic traits in Duroc pigs. A total of 38 candidate selection regions were detected by combining the fixation index and the Composite Likelihood Ratio methods. Further genome-wide association study revealed 7 associated SNPs that were related with intramuscular fat content and feed conversion ratio traits, respectively...
September 20, 2018: G3: Genes—Genomes—Genetics
Yeni L Bernal Rubio, Agustin González Reymúndez, Kuan-Han H Wu, Corinne E Griguer, Juan P Steibel, Gustavo de Los Campos, Andrea Doseff, Kathleen Gallo, Ana I Vazquez
Glioblastoma multiforme (GBM) has been recognized as the most lethal type of malignant brain tumor. Despite efforts of the medical and research community, patients' survival remains extremely low. Multi-omic profiles (including DNA sequence, methylation and gene expression) provide rich information about the tumor. These profiles are likely to reveal processes that may be predictive of patient survival. However, the integration of multi-omic profiles, which are high dimensional and heterogeneous in nature, poses great challenges...
September 18, 2018: G3: Genes—Genomes—Genetics
Han Wang, Heenam Park, Jonathan Liu, Paul W Sternberg
Null mutants are essential for analyzing gene function. Here, we describe a simple and efficient method to generate Caenorhabditis elegans null mutants using CRISPR/Cas9 and short single stranded DNA oligo repair templates to insert a universal 43-nucleotide-long knock-in cassette (STOP-IN) into the early exons of target genes. This STOP-IN cassette has stop codons in all three reading frames and leads to frameshifts, which will generate putative null mutations regardless of the reading frame of the insertion position in exons...
September 17, 2018: G3: Genes—Genomes—Genetics
Jinliang Yang, Cheng-Ting Eddy Yeh, Raghuprakash Kastoori Ramamurthy, Xinshuai Qi, Rohan L Fernando, Jack C M Dekkers, Dorian J Garrick, Dan Nettleton, Patrick S Schnable
Advances in next generation sequencing technologies and statistical approaches enable genome-wide dissection of phenotypic traits via genome-wide association studies (GWAS). Although multiple statistical approaches for conducting GWAS are available, the power and cross-validation rates of many approaches have been mostly tested using simulated data. Empirical comparisons of single variant (SV) and multi-variant (MV) GWAS approaches have not been conducted to test if a single approach or a combination of SV and MV is effective, through identification and cross-validation of trait associated loci...
September 13, 2018: G3: Genes—Genomes—Genetics
Nhan Huynh, Jie Zeng, Wen Liu, Kirst King-Jones
Targeting gene function with spatial or temporal specificity is a key goal in molecular genetics. CRISPR-Cas9 has greatly facilitated this strategy, but some standard approaches are problematic. For instance, simple tissue-specific or global overexpression of Cas9 can cause significant lethality or developmental delays even in the absence of gRNAs. In particular, we found that Gal4-mediated expression of UAS-Cas9 in the Drosophila prothoracic gland (PG) was not a suitable strategy to disrupt gene expression, since Cas9 alone caused widespread lethality...
September 13, 2018: G3: Genes—Genomes—Genetics
Ömur Kayikci, Paul M Magwene
The cyclic AMP - Protein Kinase A (cAMP-PKA) pathway is an evolutionarily conserved eukaryotic signaling network that is essential for growth and development. In the fungi, cAMP-PKA signaling plays a critical role in regulating cellular physiology and morphological switches in response to nutrient availability. We undertook a comparative investigation of the role that cAMP-PKA signaling plays in the regulation of filamentous growth in two closely related budding yeast species, Saccharomyces cerevisiae and Saccharomyces bayanus Using chemical and genetic perturbations of this pathway and its downstream targets we discovered divergent roles for cAMP-PKA signaling in the regulation of filamentous growth...
September 13, 2018: G3: Genes—Genomes—Genetics
Theodore W Peters, Christopher S Nelson, Akos A Gerencser, Kathleen J Dumas, Brandon Tavshanjian, Kyu Chul Chang, Gordon J Lithgow, Robert E Hughes
A feature common to late onset proteinopathic disorders is an accumulation of toxic protein conformers and aggregates in affected tissues. In the search for potential drug targets, many studies used high-throughput screens to find genes that modify the cytotoxicity of misfolded proteins. A complement to the latter approach is to focus on strategies that use protein aggregation as a phenotypic readout to identify pathways that control aggregate formation and maintenance. Here we use natural variation between strains of budding yeast to genetically map loci that influence the aggregation of a polyglutamine-containing protein derived from a mutant form of huntingtin, the causative agent in Huntington disease...
September 11, 2018: G3: Genes—Genomes—Genetics
Liang-Yu Lin, Sunny Chun-Chang, Jim O'Hearn, Simon T Hui, Marcus Seldin, Pritha Gupta, Galyna Bondar, Mario Deng, Raimo Jauhiainen, Johanna Kuusisto, Markku Laakso, Janet S Sinsheimer, Arjun Deb, Christoph Rau, Shuxun Ren, Yibin Wang, Aldons J Lusis, Jessica J Wang, Adriana Huertas-Vazquez
We describe a simple bioinformatics method for biomarker discovery that is based on the analysis of global transcript levels in a population of inbred mouse strains showing variation for disease-related traits. This method has advantages such as controlled environment and accessibility to heart and plasma tissue in the preclinical selection stage. We illustrate the approach by identifying candidate heart failure (HF) biomarkers by overlaying mouse transcriptome and clinical traits from 91 Hybrid Mouse Diversity Panel (HMDP) inbred strains and human HF transcriptome from the Myocardial Applied Genomics Network (MAGNet) consortium...
September 10, 2018: G3: Genes—Genomes—Genetics
Harry Klein, Yuguo Xiao, Phillip A Conklin, Rajanikanth Govindarajulu, Jacob A Kelly, Michael J Scanlon, Clinton J Whipple, Madelaine Bartlett
Forward genetics remains a powerful method for revealing the genes underpinning organismal form and function, and for revealing how these genes are tied together in gene networks. In maize, forward genetics has been tremendously successful, but the size and complexity of the maize genome made identifying mutant genes an often arduous process with traditional methods. The next generation sequencing revolution has allowed for the gene cloning process to be significantly accelerated in many organisms, even when genomes are large and complex...
September 7, 2018: G3: Genes—Genomes—Genetics
Daisuke Ogawa, Yasunori Nonoue, Hiroshi Tsunematsu, Noriko Kanno, Toshio Yamamoto, Jun-Ichi Yonemaru
A majority of traits are determined by multiple quantitative trait loci (QTLs) that can have pleiotropic effects. A multi-parent advanced generation inter-cross (MAGIC) population is well suited for genetically analyzing the effects of multiple QTLs on traits of interest because it contains a higher number of QTL alleles than a biparental population. We previously produced the JAPAN-MAGIC (JAM) population, derived from eight rice ( Oryza sativa L.) cultivars with high yield and biomass in Japan, and developed the method of genome-wide association study (GWAS) using haplotype information on the JAM lines...
September 7, 2018: G3: Genes—Genomes—Genetics
Emre Karaman, Mogens S Lund, Mahlet T Anche, Luc Janss, Guosheng Su
Implicit assumption of common (co)variance for all loci in multi-trait Genomic Best Linear Unbiased Prediction (GBLUP) results in a genomic relationship matrix (G) that is common to all traits. When this assumption is violated, Bayesian whole genome regression methods may be superior to GBLUP by accounting for unequal (co)variance for all loci or genome regions. This study aimed to develop a strategy to improve the accuracy of GBLUP for multi-trait genomic prediction, using (co)variance estimates of SNP effects from Bayesian whole genome regression methods...
September 7, 2018: G3: Genes—Genomes—Genetics
Paul Battlay, Pontus B Leblanc, Llewellyn Green, Nandita R Garud, Joshua M Schmidt, Alexandre Fournier-Level, Charles Robin
Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweeps to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid)...
September 6, 2018: G3: Genes—Genomes—Genetics
David Duneau, Haina Sun, Jonathan Revah, Keri San Miguel, Henry D Kunerth, Ian V Caldas, Philipp W Messer, Jeffrey G Scott, Nicolas Buchon
Resistance to insecticides has evolved in multiple insect species, leading to increased application rates and even control failures. Understanding the genetic basis of insecticide resistance is fundamental for mitigating its impact on crop production and disease control. We performed a GWAS approach with the Drosophila Genetic Reference Panel (DGRP) to identify the mutations involved in resistance to two widely used classes of insecticides: organophosphates (OPs, parathion) and pyrethroids (deltamethrin). Most variation in parathion resistance was associated with mutations in the target gene Ace , while most variation in deltamethrin resistance was associated with mutations in Cyp6a23 , a gene encoding a detoxification enzyme never previously associated with resistance...
September 6, 2018: G3: Genes—Genomes—Genetics
Roberta B Andrade, Marcos A T Amador, Giovanna C Cavalcante, Luciana P C Leitão, Marianne R Fernandes, Antônio A C Modesto, Fabiano C Moreira, André S Khayat, Paulo P Assumpção, Ândrea Ribeiro-Dos-Santos, Sidney Santos, Ney P C Santos
Estimates of different ancestral proportions in admixed populations are very important in population genetics studies, especially for the detection of population substructure effects in studies of case-control associations. Brazil is one of the most heterogeneous countries in the world, both from a socio-cultural and a genetic point of view. In this work, we investigated a previously developed set of 61 ancestry informative markers (AIM), aiming to estimate the proportions of four different ancestral groups (African, European, Native American and Asian) in Brazilian populations...
September 5, 2018: G3: Genes—Genomes—Genetics
Kerry L Gendreau, Benjamin A Unruh, Chuanli Zhou, Shihoko Kojima
Dynamic control of gene expression is a hallmark of the circadian system. In mouse liver, approximately 5-20% of RNAs are expressed rhythmically, and over 50% of mouse genes are rhythmically expressed in at least one tissue. Recent genome-wide analyses unveiled that, in addition to rhythmic transcription, various post-transcriptional mechanisms play crucial roles in driving rhythmic gene expression. Alternative polyadenylation (APA) is an emerging post-transcriptional mechanism that changes the 3'-ends of transcripts by alternating poly(A) site usage...
September 4, 2018: G3: Genes—Genomes—Genetics
Daniel Oreper, Sarah A Schoenrock, Rachel McMullan, Robin Ervin, Joseph Farrington, Darla R Miller, Fernando Pardo-Manuel de Villena, William Valdar, Lisa M Tarantino
Parent-of-origin effects (POE) in mammals typically arise from maternal effects or imprinting. In some instances, such POE have been associated with psychiatric disorders, as well as with changes in a handful of animal behaviors. However, POE on complex traits such as behavior remain largely uncharacterized. Moreover, although both behavior and epigenetic effects are known to be modified by perinatal environmental exposures such as nutrient deficiency, the architecture of such environment-by-POE is mostly unexplored...
August 31, 2018: G3: Genes—Genomes—Genetics
Jenna Whalen, Courtney Sniffen, Siobhan Gartland, Michael Vannini, Anupama Seshan
The proper regulation of cell cycle transitions is paramount to the maintenance of cellular genome integrity. In Saccharomyces cerevisiae , the mitotic exit network (MEN) is a Ras-like signaling cascade that effects the transition from M phase to G1 during the cell division cycle in budding yeast. MEN activation is tightly regulated. It occurs during anaphase and is coupled to mitotic spindle position by the spindle position checkpoint (SPoC). Bfa1 is a key component of the SPoC and functions as part of a two-component GAP complex along with Bub2...
August 30, 2018: G3: Genes—Genomes—Genetics
Zhaofa Xu, Yiman Hu, Yajun Deng, Yutao Chen, Hanqi Hua, Siyu Huang, Qian Nie, Qian Pan, Dengke K Ma, Long Ma
Animals utilize conserved mechanisms to regulate oxidative stress. The Caenorhabditis elegans SKN-1 protein is homologous to the vertebrate Nrf (NF-E2-related factor) family of cap 'n' collar (CnC) transcription factors and functions as a core regulator of xenobiotic and oxidative stress responses. The WD40 repeat-containing protein WDR-23 is a key negative regulator of SKN-1 activity. We previously found that the oxidative stress induced by excess iodide can be relieved by loss of function in the BLI-3/TSP-15/DOXA-1 dual oxidase complex...
August 30, 2018: G3: Genes—Genomes—Genetics
Sarah Eberle, Djeneba Dezoumbe, Rhegan McGregor, Shane Kinzer, Whitney Raver, Sarah Schaack, Leigh C Latta
Understanding the context-dependence of spontaneous mutations is crucial to predicting evolutionary trajectories. In this experiment, the impact of genetic background and trait-type on mutational susceptibility was investigated. Mutant and non-mutant lines of six unique genotypes from two populations of Daphnia magna were phenotypically assayed using a common-garden experiment. Morphological, life-history, and behavioral traits were measured and estimates of the mutation parameters were generated. The mutation parameters varied between the populations and among genotypes, suggesting differential susceptibility to mutation depending upon genomic background...
August 29, 2018: G3: Genes—Genomes—Genetics
Kwan Yin Lee, Mathieu Ranger, Marc D Meneghini
Much of euchromatin regulation occurs through reversible methylation of histone H3 lysine-4 and lysine-36 (H3K4me and H3K36me). Using the budding yeast Saccharomyces cerevisiae , we previously found that levels of H3K4me modulated temperature sensitive alleles of the transcriptional elongation complex Spt6-Spn1 through an unknown H3K4me effector pathway. Here we identify the Rpd3S histone deacetylase complex as the H3K4me effector underlying these Spt6-Spn1 genetic interactions. Exploiting these Spt6-Spn1 genetic interactions, we show that H3K4me and H3K36me collaboratively impact Rpd3S function in an opposing manner...
August 29, 2018: G3: Genes—Genomes—Genetics
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