Axon Termination, Pruning, and Synaptogenesis in the Giant Fiber System of Drosophila melanogaster Is Promoted by Highwire [Developmental and Behavioral Genetics]
The ubiquitin ligase Highwire has a conserved role in synapse formation. Here, we show that Highwire coordinates several facets of central synapse formation in the Drosophila melanogaster giant fiber system, including axon termination, axon pruning, and synaptic function. Despite the similarities to the fly neuromuscular junction, the role of Highwire and the underlying signaling pathways are distinct in the fly’s giant fiber system. During development, branching of the giant fiber presynaptic terminal occurs and, normally, the transient branches are pruned away. However, in highwire mutants these ectopic branches pe...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Borgen, M., Rowland, K., Boerner, J., Lloyd, B., Khan, A., Murphey, R. Tags: Developmental and Behavioral Genetics Source Type: research
Sexual Dimorphism of Body Size Is Controlled by Dosage of the X-Chromosomal Gene Myc and by the Sex-Determining Gene tra in Drosophila [Developmental and Behavioral Genetics]
Drosophila females are larger than males. In this article, we describe how X-chromosome dosage drives sexual dimorphism of body size through two means: first, through unbalanced expression of a key X-linked growth-regulating gene, and second, through female-specific activation of the sex-determination pathway. X-chromosome dosage determines phenotypic sex by regulating the genes of the sex-determining pathway. In the presence of two sets of X-chromosome signal elements (XSEs), Sex-lethal (Sxl) is activated in female (XX) but not male (XY) animals. Sxl activates transformer (tra), a gene that encodes a splicing factor essen...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Mathews, K. W., Cavegn, M., Zwicky, M. Tags: Developmental and Behavioral Genetics Source Type: research
The Role of the UNC-82 Protein Kinase in Organizing Myosin Filaments in Striated Muscle of Caenorhabditis elegans [Cellular Genetics]
We present evidence that the interaction of UNC-98/ZnF with myosin A is independent of UNC-82, and that UNC-82 acts upstream of UNC-98/ZnF in a pathway that organizes paramyosin during thick filament assembly. (Source: Genetics)
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Schiller, N. R., Duchesneau, C. D., Lane, L. S., Reedy, A. R., Manzon, E. R., Hoppe, P. E. Tags: Cellular Genetics Source Type: research
Nutritional Control of Chronological Aging and Heterochromatin in Saccharomyces cerevisiae [Cellular Genetics]
Calorie restriction extends life span in organisms as diverse as yeast and mammals through incompletely understood mechanisms.The role of NAD+-dependent deacetylases known as Sirtuins in this process, particularly in the yeast Saccharomyces cerevisiae, is controversial. We measured chronological life span of wild-type and sir2 strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2 extended life span in high glucose complete minimal medium and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie-restriction response under these conditions. Ex...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: McCleary, D. F., Rine, J. Tags: Cellular Genetics Source Type: research
Premature Silencing of the Spindle Assembly Checkpoint Is Prevented by the Bub1-H2A-Sgo1-PP2A Axis in Saccharomyces cerevisiae [Cellular Genetics]
The spindle assembly checkpoint (SAC) monitors mistakes in kinetochore-microtubule interaction and its activation prevents anaphase entry. The SAC remains active until all chromosomes have achieved bipolar attachment which applies tension on kinetochores. Our previous data in budding yeast Saccharomyces cerevisiae show that Ipl1/Aurora B kinase and a centromere-associated protein, Sgo1, are required to prevent SAC silencing prior to tension generation, but we believe that this regulatory network is incomplete. Bub1 kinase is one of the SAC components, and Bub1-dependent H2A phosphorylation triggers centromere recruitment o...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Jin, F., Bokros, M., Wang, Y. Tags: Cellular Genetics Source Type: research
A Role for the Twins Protein Phosphatase (PP2A-B55) in the Maintenance of Drosophila Genome Integrity [Cellular Genetics]
The protein phosphatase 2A (PP2A) is a conserved heterotrimeric enzyme that regulates several cellular processes including the DNA damage response and mitosis. Consistent with these functions, PP2A is mutated in many types of cancer and acts as a tumor suppressor. In mammalian cells, PP2A inhibition results in DNA double strand breaks (DSBs) and chromosome aberrations (CABs). However, the mechanisms through which PP2A prevents DNA damage are still unclear. Here, we focus on the role of the Drosophila twins (tws) gene in the maintenance of chromosome integrity; tws encodes the B regulatory subunit (B/B55) of PP2A. Mutations...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Merigliano, C., Marzio, A., Renda, F., Somma, M. P., Gatti, M., Verni, F. Tags: Cellular Genetics Source Type: research
Involvement of Conserved Amino Acids in the C-Terminal Region of LINE-1 ORF2p in Retrotransposition [Cellular Genetics]
Long interspersed element 1 (L1) is the only currently active autonomous retroelement in the human genome. Along with the parasitic SVA and short interspersed element Alu, L1 is the source of DNA damage induced by retrotransposition: a copy-and-paste process that has the potential to disrupt gene function and cause human disease. The retrotransposition process is dependent upon the ORF2 protein (ORF2p). However, it is unknown whether most of the protein is important for retrotransposition. In particular, other than the Cys motif, the C terminus of the protein has not been intensely examined in the context of retrotransposi...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Christian, C. M., Sokolowski, M., deHaro, D., Kines, K. J., Belancio, V. P. Tags: Cellular Genetics Source Type: research
Chromatin Regulation by the NuA4 Acetyltransferase Complex Is Mediated by Essential Interactions Between Enhancer of Polycomb (Epl1) and Esa1 [Gene Expression]
Enzymes that modify and remodel chromatin act in broadly conserved macromolecular complexes. One key modification is the dynamic acetylation of histones and other chromatin proteins by opposing activities of acetyltransferase and deacetylase complexes. Among acetyltransferases, the NuA4 complex containing Tip60 or its Saccharomyces cerevisiae ortholog Esa1 is of particular significance because of its roles in crucial genomic processes including DNA damage repair and transcription. The catalytic subunit Esa1 is essential, as are five noncatalytic NuA4 subunits. We found that of the noncatalytic subunits, deletion of Enhance...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Searle, N. E., Torres-Machorro, A. L., Pillus, L. Tags: Gene Expression Source Type: research
Histone H3K4 and H3K36 Methylation Independently Recruit the NuA3 Histone Acetyltransferase in Saccharomyces cerevisiae [Gene Expression]
Histone post-translational modifications (PTMs) alter chromatin structure by promoting the interaction of chromatin-modifying complexes with nucleosomes. The majority of chromatin-modifying complexes contain multiple domains that preferentially interact with modified histones, leading to speculation that these domains function in concert to target nucleosomes with distinct combinations of histone PTMs. In Saccharomyces cerevisiae, the NuA3 histone acetyltransferase complex contains three domains, the PHD finger in Yng1, the PWWP domain in Pdp3, and the YEATS domain in Taf14; which in vitro bind to H3K4 methylation, H3K36 m...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Martin, B. J. E., McBurney, K. L., Maltby, V. E., Jensen, K. N., BrindAmour, J., Howe, L. J. Tags: Gene Expression Source Type: research
Meiotic Crossing Over in Maize Knob Heterochromatin [Genome Integrity and Transmission]
There is ample evidence that crossing over is suppressed in heterochromatin associated with centromeres and nucleolus organizers (NORs). This characteristic has been attributed to all heterochromatin, but the generalization may not be justified. To investigate the relationship of crossing over to heterochromatin that is not associated with centromeres or NORs, we used a combination of fluorescence in situ hybridization of the maize 180-bp knob repeat to show the locations of knob heterochromatin and fluorescent immunolocalization of MLH1 protein and AFD1 protein to show the locations of MLH1 foci on maize synaptonemal comp...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Stack, S. M., Shearer, L. A., Lohmiller, L., Anderson, L. K. Tags: Genome Integrity and Transmission Source Type: research
Meiotic Consequences of Genetic Divergence Across the Murine Pseudoautosomal Region [Genome Integrity and Transmission]
The production of haploid gametes during meiosis is dependent on the homology-driven processes of pairing, synapsis, and recombination. On the mammalian heterogametic sex chromosomes, these key meiotic activities are confined to the pseudoautosomal region (PAR), a short region of near-perfect sequence homology between the X and Y chromosomes. Despite its established importance for meiosis, the PAR is rapidly evolving, raising the question of how proper X/Y segregation is buffered against the accumulation of homology-disrupting mutations. Here, I investigate the interplay of PAR evolution and function in two interfertile ho...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Dumont, B. L. Tags: Genome Integrity and Transmission Source Type: research
Detecting High-Order Epistasis in Nonlinear Genotype-Phenotype Maps [Statistical Genetics and Genomics]
High-order epistasis has been observed in many genotype-phenotype maps. These multi-way interactions between mutations may be useful for dissecting complex traits and could have profound implications for evolution. Alternatively, they could be a statistical artifact. High-order epistasis models assume the effects of mutations should add, when they could in fact multiply or combine in some other nonlinear way. A mismatch in the "scale" of the epistasis model and the scale of the underlying map would lead to spurious epistasis. In this article, we develop an approach to estimate the nonlinear scales of arbitrary genotype-phe...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Sailer, Z. R., Harms, M. J. Tags: Statistical Genetics and Genomics Source Type: research
Efficient Estimation of Realized Kinship from Single Nucleotide Polymorphism Genotypes [Statistical Genetics and Genomics]
Realized kinship is a key statistic in analyses of genetic data involving relatedness of individuals or structure of populations. There are several estimators of kinship that make use of dense SNP genotypes. We introduce a class of estimators, of which some existing estimators are special cases. Within this class, we derive properties of the estimators and determine an optimal estimator. Additionally, we introduce an alternative marker weighting that takes allelic associations [linkage disequilibrium (LD)] into account, and apply this weighting to several estimators. In a simulation study, we show that improved estimators ...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Wang, B., Sverdlov, S., Thompson, E. Tags: Statistical Genetics and Genomics Source Type: research
A Robust and Powerful Set-Valued Approach to Rare Variant Association Analyses of Secondary Traits in Case-Control Sequencing Studies [Statistical Genetics and Genomics]
In many case-control designs of genome-wide association (GWAS) or next generation sequencing (NGS) studies, extensive data on secondary traits that may correlate and share the common genetic variants with the primary disease are available. Investigating these secondary traits can provide critical insights into the disease etiology or pathology, and enhance the GWAS or NGS results. Methods based on logistic regression (LG) were developed for this purpose. However, for the identification of rare variants (RVs), certain inadequacies in the LG models and algorithmic instability can cause severely inflated type I error, an...
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Kang, G., Bi, W., Zhang, H., Pounds, S., Cheng, C., Shete, S., Zou, F., Zhao, Y., Zhang, J.-F., Yue, W. Tags: Statistical Genetics and Genomics Source Type: research
Simultaneous Modeling of Disease Status and Clinical Phenotypes To Increase Power in Genome-Wide Association Studies [Methods, Technology, and Resources]
We present a novel method that resolves both of these issues for simultaneous association testing of genetic variants that have both case status and a clinical covariate. We demonstrate the utility of our method using both simulated data and the Northern Finland Birth Cohort data. (Source: Genetics)
Source: Genetics - March 6, 2017 Category: Genetics & Stem Cells Authors: Bilow, M., Crespo, F., Pan, Z., Eskin, E., Eyheramendy, S. Tags: Methods, Technology, and Resources Source Type: research
