Extended Synaptotagmin Localizes to Presynaptic ER and Promotes Neurotransmission and Synaptic Growth in Drosophila [Cellular Genetics]
The endoplasmic reticulum (ER) is an extensive organelle in neurons with important roles at synapses including the regulation of cytosolic Ca2+, neurotransmission, lipid metabolism, and membrane trafficking. Despite intriguing evidence for these crucial functions, how the presynaptic ER influences synaptic physiology remains enigmatic. To gain insight into this question, we have generated and characterized mutations in the single extended synaptotagmin (Esyt) ortholog in Drosophila melanogaster. Esyts are evolutionarily conserved ER proteins with Ca2+-sensing domains that have recently been shown to orchestrate membrane te...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Kikuma, K., Li, X., Kim, D., Sutter, D., Dickman, D. K. Tags: Cellular Genetics Source Type: research

Diversification of Transcriptional Regulation Determines Subfunctionalization of Paralogous Branched Chain Aminotransferases in the Yeast Saccharomyces cerevisiae [Gene Expression]
Saccharomyces cerevisiae harbors BAT1 and BAT2 paralogous genes that encode branched chain aminotransferases and have opposed expression profiles and physiological roles . Accordingly, in primary nitrogen sources such as glutamine, BAT1 expression is induced, supporting Bat1-dependent valine–isoleucine–leucine (VIL) biosynthesis, while BAT2 expression is repressed. Conversely, in the presence of VIL as the sole nitrogen source, BAT1 expression is hindered while that of BAT2 is activated, resulting in Bat2-dependent VIL catabolism. The presented results confirm that BAT1 expression is determined by transcription...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Gonzalez, J., Lopez, G., Argueta, S., Escalera-Fanjul, X., el Hafidi, M., Campero-Basaldua, C., Strauss, J., Riego-Ruiz, L., Gonzalez, A. Tags: Gene Expression Source Type: research

A Key Regulator of the Glycolytic and Gluconeogenic Central Metabolic Pathways in Sinorhizobium meliloti [Gene Expression]
The order Rhizobiales contains numerous agriculturally, biotechnologically, and medically important bacteria, including the rhizobia, and the genera Agrobacterium, Brucella, and Methylobacterium, among others. These organisms tend to be metabolically versatile, but there has been relatively little investigation into the regulation of their central carbon metabolic pathways. Here, RNA-sequencing and promoter fusion data are presented to show that the PckR protein is a key regulator of central carbon metabolism in Sinorhizobium meliloti; during growth with gluconeogenic substrates, PckR represses expression of the complete E...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: diCenzo, G. C., Muhammed, Z., Osteras, M., OBrien, S. A. P., Finan, T. M. Tags: Gene Expression Source Type: research

Chromosome Healing Is Promoted by the Telomere Cap Component Hiphop in Drosophila [Genome Integrity and Transmission]
The addition of a new telomere onto a chromosome break, a process termed healing, has been studied extensively in organisms that utilize telomerase to maintain their telomeres. In comparison, relatively little is known about how new telomeres are constructed on broken chromosomes in organisms that do not use telomerase. Chromosome healing was studied in somatic and germline cells of Drosophila melanogaster, a nontelomerase species. We observed, for the first time, that broken chromosomes can be healed in somatic cells. In addition, overexpression of the telomere cap component Hiphop increased the survival of somatic cells ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Kurzhals, R. L., Fanti, L., Ebsen, A. C. G., Rong, Y. S., Pimpinelli, S., Golic, K. G. Tags: Genome Integrity and Transmission Source Type: research

Rapid DNA Synthesis During Early Drosophila Embryogenesis Is Sensitive to Maternal Humpty Dumpty Protein Function [Genome Integrity and Transmission]
This study reveals that maternally encoded Humpty dumpty protein is essential for DNA replication and genome integrity during the little-understood embryonic S/M cycles. Moreover, the two hd272-9 maternal-effect phenotypes suggest that ovarian gene amplification and embryonic cleavage are two time periods in development that are particularly sensitive to mild deficits in DNA replication function. This last observation has broader relevance for interpreting why mild mutations in the human ortholog of humpty dumpty and other DNA replication genes cause tissue-specific malformations of microcephalic dwarfisms. (Source: Genetics)
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Lesly, S., Bandura, J. L., Calvi, B. R. Tags: Genome Integrity and Transmission Source Type: research

The Role of Blm Helicase in Homologous Recombination, Gene Conversion Tract Length, and Recombination Between Diverged Sequences in Drosophila melanogaster [Genome Integrity and Transmission]
DNA double-strand breaks (DSBs) are a particularly deleterious class of DNA damage that threatens genome integrity. DSBs are repaired by three pathways: nonhomologous-end joining (NHEJ), homologous recombination (HR), and single-strand annealing (SSA). Drosophila melanogaster Blm (DmBlm) is the ortholog of Saccharomyces cerevisiae SGS1 and human BLM, and has been shown to suppress crossovers in mitotic cells and repair mitotic DNA gaps via HR. To further elucidate the role of DmBlm in repair of a simple DSB, and in particular recombination mechanisms, we utilized the Direct Repeat of white (DR-white) and Direct Repeat of w...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Ertl, H. A., Russo, D. P., Srivastava, N., Brooks, J. T., Dao, T. N., LaRocque, J. R. Tags: Genome Integrity and Transmission Source Type: research

Autosomal Trisomy and Triploidy Are Corrected During Female Meiosis in Caenorhabditis elegans [Genome Integrity and Transmission]
This study reveals a pathway that allows aneuploid parents to produce euploid offspring at higher than random frequency. (Source: Genetics)
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Vargas, E., McNally, K., Friedman, J. A., Cortes, D. B., Wang, D. Y., Korf, I. F., McNally, F. J. Tags: Genome Integrity and Transmission Source Type: research

A Powerful Variant-Set Association Test Based on Chi-Square Distribution [Statistical Genetics and Genomics]
Detecting the association between a set of variants and a given phenotype has attracted a large amount of attention in the scientific community, although it is a difficult task. Recently, several related statistical approaches have been proposed in the literature; powerful statistical tests are still highly desired and yet to be developed in this area. In this paper, we propose a powerful test that combines information from each individual single nucleotide polymorphism (SNP) based on principal component analysis without relying on the eigenvalues associated with the principal components. We compare the proposed approach w...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Chen, Z., Lin, T., Wang, K. Tags: Statistical Genetics and Genomics Source Type: research

A Powerful Framework for Integrating eQTL and GWAS Summary Data [Statistical Genetics and Genomics]
Two new gene-based association analysis methods, called PrediXcan and TWAS for GWAS individual-level and summary data, respectively, were recently proposed to integrate GWAS with eQTL data, alleviating two common problems in GWAS by boosting statistical power and facilitating biological interpretation of GWAS discoveries. Based on a novel reformulation of PrediXcan and TWAS, we propose a more powerful gene-based association test to integrate single set or multiple sets of eQTL data with GWAS individual-level data or summary statistics. The proposed test was applied to several GWAS datasets, including two lipid summary asso...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Xu, Z., Wu, C., Wei, P., Pan, W. Tags: Statistical Genetics and Genomics Source Type: research

COMBAT: A Combined Association Test for Genes Using Summary Statistics [Statistical Genetics and Genomics]
Genome-wide association studies (GWAS) have been widely used for identifying common variants associated with complex diseases. Traditional analysis of GWAS typically examines one marker at a time, usually single nucleotide polymorphisms (SNPs), to identify individual variants associated with a disease. However, due to the small effect sizes of common variants, the power to detect individual risk variants is generally low. As a complementary approach to SNP-level analysis, a variety of gene-based association tests have been proposed. However, the power of existing gene-based tests is often dependent on the underlying geneti...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Wang, M., Huang, J., Liu, Y., Ma, L., Potash, J. B., Han, S. Tags: Statistical Genetics and Genomics Source Type: research

AdmixPower: Statistical Power and Sample Size Estimation for Mapping Genetic Loci in Admixed Populations [Methods, Technology, and Resources]
Admixed populations result from recent admixture of two or more ancestral populations with divergent allele frequencies. The genome of each admixed individual is a mosaic of haplotypes inherited from the ancestral populations. Despite the substantial work to assess power and sample size requirements for association mapping in genetically homogeneous populations of European ancestry, power and sample size estimation methods for mapping genes in genetically heterogeneous admixed populations such as African Americans are lacking. Admixture mapping is a method that traces the ancestral origin of disease-susceptibility genetic ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Gautam, Y., Altaye, M., Xie, C., Mersha, T. B. Tags: Methods, Technology, and Resources Source Type: research

Cell Biology of the Mitochondrion [Cell and Organelle Biology]
Mitochondria are best known for harboring pathways involved in ATP synthesis through the tricarboxylic acid cycle and oxidative phosphorylation. Major advances in understanding these roles were made with Caenorhabditis elegans mutants affecting key components of the metabolic pathways. These mutants have not only helped elucidate some of the intricacies of metabolism pathways, but they have also served as jumping off points for pharmacology, toxicology, and aging studies. The field of mitochondria research has also undergone a renaissance, with the increased appreciation of the role of mitochondria in cell processes other ...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: van der Bliek, A. M., Sedensky, M. M., Morgan, P. G. Tags: Cell and Organelle Biology Source Type: research

Moving Speciation Genetics Forward: Modern Techniques Build on Foundational Studies in Drosophila [Ecology and Evolution]
The question of how new species evolve has been examined at every level, from macroevolutionary patterns of diversification to molecular population genetic analyses of specific genomic regions between species pairs. Drosophila has been at the center of many of these research efforts. Though our understanding of the speciation process has grown considerably over the past few decades, very few genes have been identified that contribute to barriers to reproduction. The development of advanced molecular genetic and genomic methods provides promising avenues for the rapid discovery of more genes that contribute to speciation, p...
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Authors: Castillo, D. M., Barbash, D. A. Tags: Ecology and Evolution Source Type: research

ISSUE HIGHLIGHTS [Issue Highlights]
(Source: Genetics)
Source: Genetics - November 2, 2017 Category: Genetics & Stem Cells Tags: Issue Highlights Source Type: research

Up-Frameshift Protein UPF1 Regulates Neurospora crassa Circadian and Diurnal Growth Rhythms [Corrigendum]
(Source: Genetics)
Source: Genetics - October 4, 2017 Category: Genetics & Stem Cells Tags: Corrigendum Source Type: research