Remarkable Evolutionary Conservation of Antiobesity ADIPOSE/WDTC1 Homologs in Animals and Plants [Cellular Genetics]
ASG2 (Altered Seed Germination 2) is a prenylated protein in Arabidopsis thaliana that participates to abscisic acid signaling and is proposed to act as a substrate adaptor for the DDB1 (DNA damage-binding protein 1)-CUL4 (Cullin 4) E3 ubiquitin ligase complex. ASG2 harbors WD40 and TetratricoPeptide Repeat (TPR) domains, and resembles the well-conserved animal gene called ADP (antiobesity factor ADIPOSE) in fly and WDTC1 (WD40 and TPR 1) in humans. Loss of function of WDTC1 results in an increase in adipocytes, fat accumulation, and obesity. Antiadipogenic functions of WDTC1 involve regulation of fat-related gene transcri...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Ducos, E., Verges, V., Duge de Bernonville, T., Blanc, N., Giglioli-Guivarch, N., Dutilleul, C. Tags: Cellular Genetics Source Type: research
Connected Gene Communities Underlie Transcriptional Changes in Cornelia de Lange Syndrome [Gene Expression]
Cornelia de Lange syndrome (CdLS) is a complex multisystem developmental disorder caused by mutations in cohesin subunits and regulators. While its precise molecular mechanisms are not well defined, they point toward a global deregulation of the transcriptional gene expression program. Cohesin is associated with the boundaries of chromosome domains and with enhancer and promoter regions connecting the three-dimensional genome organization with transcriptional regulation. Here, we show that connected gene communities, structures emerging from the interactions of noncoding regulatory elements and genes in the three-dimension...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Boudaoud, I., Fournier, E., Baguette, A., Vallee, M., Lamaze, F. C., Droit, A., Bilodeau, S. Tags: Gene Expression Source Type: research
A Model for Epigenetic Inhibition via Transvection in the Mouse [Gene Expression]
Transvection is broadly defined as the ability of one locus to affect its homologous locus in trans. Although it was first discovered in the 1950s, there are only two known cases in mammals. Here, we report another instance of mammalian transvection induced by the Cre/LoxP system, which is widely used for conditional gene targeting in the mouse. We attempted to use the germline-expressed Vasa-Cre transgene to engineer a mouse mutation, but observe a dramatic reduction of LoxP recombination in mice that inherit an already deleted LoxP allele in trans. A similar phenomenon has previously been observed with another Cre that i...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Rodriguez, J. D., Myrick, D. A., Falciatori, I., Christopher, M. A., Lee, T. W., Hannon, G. J., Katz, D. J. Tags: Gene Expression Source Type: research
Mitotic Gene Conversion Tracts Associated with Repair of a Defined Double-Strand Break in Saccharomyces cerevisiae [Genome Integrity and Transmission]
Mitotic recombination between homologous chromosomes leads to the uncovering of recessive alleles through loss of heterozygosity. In the current study, a defined double-strand break was used to initiate reciprocal loss of heterozygosity between diverged homologs of chromosome IV in Saccharomyces cerevisiae. These events resulted from the repair of two broken chromatids, one of which was repaired as a crossover and the other as a noncrossover. Associated gene conversion tracts resulting from the donor-directed repair of mismatches formed during strand exchange (heteroduplex DNA) were mapped using microarrays. Gene conversio...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Hum, Y. F., Jinks-Robertson, S. Tags: Genome Integrity and Transmission Source Type: research
Time-Course Analysis of Early Meiotic Prophase Events Informs Mechanisms of Homolog Pairing and Synapsis in Caenorhabditis elegans [Genome Integrity and Transmission]
Segregation of homologous chromosomes during meiosis depends on their ability to reorganize within the nucleus, discriminate among potential partners, and stabilize pairwise associations through assembly of the synaptonemal complex (SC). Here we report a high-resolution time-course analysis of these key early events during Caenorhabditis elegans meiosis. Labeled nucleotides are incorporated specifically into the X chromosomes during the last 2 hr of S phase, a property we exploit to identify a highly synchronous cohort of nuclei. By tracking X-labeled nuclei through early meiotic prophase, we define the sequence and durati...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Mlynarczyk-Evans, S., Villeneuve, A. M. Tags: Genome Integrity and Transmission Source Type: research
Regulation of Lysosomal Function by the DAF-16 Forkhead Transcription Factor Couples Reproduction to Aging in Caenorhabditis elegans [Genome Integrity and Transmission]
Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans. In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signaling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity—a critical regulator of the proteoly...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Baxi, K., Ghavidel, A., Waddell, B., Harkness, T. A., de Carvalho, C. E. Tags: Genome Integrity and Transmission Source Type: research
Benchmarking Relatedness Inference Methods with Genome-Wide Data from Thousands of Relatives [Statistical Genetics and Genomics]
Inferring relatedness from genomic data is an essential component of genetic association studies, population genetics, forensics, and genealogy. While numerous methods exist for inferring relatedness, thorough evaluation of these approaches in real data has been lacking. Here, we report an assessment of 12 state-of-the-art pairwise relatedness inference methods using a data set with 2485 individuals contained in several large pedigrees that span up to six generations. We find that all methods have high accuracy (92–99%) when detecting first- and second-degree relationships, but their accuracy dwindles to <43% for ...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Ramstetter, M. D., Dyer, T. D., Lehman, D. M., Curran, J. E., Duggirala, R., Blangero, J., Mezey, J. G., Williams, A. L. Tags: Statistical Genetics and Genomics Source Type: research
Risk Prediction Modeling on Family-Based Sequencing Data Using a Random Field Method [Statistical Genetics and Genomics]
Family-based design is one of the most popular designs in genetic studies and has many unique features for risk-prediction research. It is robust against genetic heterogeneity, and the relatedness among family members can be informative for predicting an individual’s risk for disease with polygenic and shared environmental components of risk. Despite these strengths, family-based designs have been used infrequently in current risk-prediction studies, and their related statistical methods have not been well developed. In this article, we developed a generalized random field (GRF) method for family-based risk-predictio...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Wen, Y., Burt, A., Lu, Q. Tags: Statistical Genetics and Genomics Source Type: research
Analysis of Large-Scale Mutagenesis Data To Assess the Impact of Single Amino Acid Substitutions [Methods, Technology, and Resources]
Mutagenesis is a widely used method for identifying protein positions that are important for function or ligand binding. Advances in high-throughput DNA sequencing and mutagenesis techniques have enabled measurement of the effects of nearly all possible amino acid substitutions in many proteins. The resulting large-scale mutagenesis data sets offer a unique opportunity to draw general conclusions about the effects of different amino acid substitutions. Thus, we analyzed 34,373 mutations in 14 proteins whose effects were measured using large-scale mutagenesis approaches. Methionine was the most tolerated substitution, while...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Gray, V. E., Hause, R. J., Fowler, D. M. Tags: Methods, Technology, and Resources Source Type: research
Waddington Redux: De Novo Mutations Underlie the Genetic Assimilation of Stress-Induced Phenocopies in Drosophila melanogaster [Commentary]
(Source: Genetics)
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Kasinathan, B., Ahmad, K., Malik, H. S. Tags: Commentary Source Type: research
DNA Replication Control During Drosophila Development: Insights into the Onset of S Phase, Replication Initiation, and Fork Progression [Repair, Recombination, and Cell Division]
Proper control of DNA replication is critical to ensure genomic integrity during cell proliferation. In addition, differential regulation of the DNA replication program during development can change gene copy number to influence cell size and gene expression. Drosophila melanogaster serves as a powerful organism to study the developmental control of DNA replication in various cell cycle contexts in a variety of differentiated cell and tissue types. Additionally, Drosophila has provided several developmentally regulated replication models to dissect the molecular mechanisms that underlie replication-based copy number change...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Hua, B. L., Orr-Weaver, T. L. Tags: Repair, Recombination, and Cell Division Source Type: research
Model Organisms Facilitate Rare Disease Diagnosis and Therapeutic Research [Review]
Efforts to identify the genetic underpinnings of rare undiagnosed diseases increasingly involve the use of next-generation sequencing and comparative genomic hybridization methods. These efforts are limited by a lack of knowledge regarding gene function, and an inability to predict the impact of genetic variation on the encoded protein function. Diagnostic challenges posed by undiagnosed diseases have solutions in model organism research, which provides a wealth of detailed biological information. Model organism geneticists are by necessity experts in particular genes, gene families, specific organs, and biological functio...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Wangler, M. F., Yamamoto, S., Chao, H.-T., Posey, J. E., Westerfield, M., Postlethwait, J., Members of the Undiagnosed Diseases Network (UDN), Hieter, P., Boycott, K. M., Campeau, P. M., Bellen, H. J. Tags: Review Source Type: research
Mendelism: New Insights from Gregor Mendels Lectures in Brno [Perspectives]
Interpretation of Gregor Mendel’s work has previously been based on study of his published paper "Experiments in Plant Hybridization." In contrast, the lectures that he gave preceding publication of this work have been largely neglected for more than 150 years. Here, we report on and interpret the content of Mendel’s previous two lectures, as they were reported in a local newspaper. We comprehensively reference both the text of his paper and the historical background of his experiments. Our analysis shows that while Mendel had inherited the traditional research program on interspecific hybridization in plants, ...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Zhang, H., Chen, W., Sun, K. Tags: Perspectives Source Type: research
ISSUE HIGHLIGHTS [Issue Highlights]
(Source: Genetics)
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Tags: Issue Highlights Source Type: research
Corrigendum [Corrigendum]
(Source: Genetics)
Source: Genetics - August 4, 2017 Category: Genetics & Stem Cells Tags: Corrigendum Source Type: research
