The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years.
Abstract Multiple sclerosis (MS) is a common autoimmune disease that targets myelin in the central nervous system (CNS). Multiple genome-wide association studies (GWAS) over the past 10 years have uncovered more than 200 loci that independently contribute to disease pathogenesis. As with many other complex diseases, risk of developing MS is driven by multiple common variants whose biological effects are not immediately clear. Here, we present a historical perspective on the progress made in MS genetics and discuss current work geared towards creating a more complete model that accurately represents the genetic lan...
Source: Trends in Genetics : TIG - October 5, 2017 Category: Genetics & Stem Cells Authors: Baranzini SE, Oksenberg JR Tags: Trends Genet Source Type: research

The Mobile World of Transposable Elements.
PMID: 28987267 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - October 5, 2017 Category: Genetics & Stem Cells Authors: Navarro C Tags: Trends Genet Source Type: research

Choosing the Active X: The Human Version of X Inactivation.
Abstract Humans and rodents differ in how they carry out X inactivation (XI), the mammalian method to compensate for the different number of X chromosomes in males and females. Evolutionary changes in staging embryogenesis and in mutations within the XI center alter the process among mammals. The mouse model of XI is predicated on X counting and subsequently choosing the X to 'inactivate'. However, new evidence suggests that humans initiate XI by protecting one X in both sexes from inactivation by XIST, the noncoding RNA that silences the inactive X. This opinion article explores the question of how the inactive X...
Source: Trends in Genetics : TIG - October 5, 2017 Category: Genetics & Stem Cells Authors: Migeon BR Tags: Trends Genet Source Type: research

SAMHD1 Sheds Moonlight on DNA Double-Strand Break Repair.
Abstract SAMHD1 (sterile α motif and histidine (H) aspartate (D) domain-containing protein 1) is known for its antiviral activity of hydrolysing deoxynucleotides required for virus replication. Daddacha et al. identify a hydrolase-independent, moonlighting function of SAMHD1 that facilitates homologous recombination of DNA double-strand breaks (DSBs) by promoting recruitment of C-terminal binding protein interacting protein (CTIP), a DNA-end resection factor, to damaged DNA. These findings could benefit anticancer treatment. PMID: 28969870 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 29, 2017 Category: Genetics & Stem Cells Authors: Cabello-Lobato MJ, Wang S, Schmidt CK Tags: Trends Genet Source Type: research

Alternative Lengthening of Telomeres: DNA Repair Pathways Converge.
Abstract Telomeres shorten during each cellular division, with cumulative attrition resulting in telomeric damage and replicative senescence. Bypass of replicative senescence precipitates catastrophic telomere shortening or crisis, and is characterized by widespread genomic instability. Activation of a telomere maintenance mechanism (TMM) is necessary to stabilise the genome and establish cellular immortality through the reconstitution of telomere capping function. The alternative lengthening of telomeres (ALT) pathway is a TMM frequently activated in tumors of mesenchymal or neuroepithelial origin. ALT is a homol...
Source: Trends in Genetics : TIG - September 29, 2017 Category: Genetics & Stem Cells Authors: Sobinoff AP, Pickett HA Tags: Trends Genet Source Type: research

piRNA Biogenesis in Drosophila melanogaster.
in AA Abstract The PIWI-interacting RNA (piRNA) pathway is a conserved defense system that protects the genome integrity of the animal germline from deleterious transposable elements. Targets of silencing are recognized by small noncoding piRNAs that are processed from long precursor molecules. Although piRNAs and other classes of small noncoding RNAs, such as miRNAs and small interfering (si)RNAs, interact with members of the same family of Argonaute (Ago) proteins and their function in target repression is similar, the biogenesis of piRNAs differs from those of the other two small RNAs. Recently, many aspects of...
Source: Trends in Genetics : TIG - September 27, 2017 Category: Genetics & Stem Cells Authors: Huang X, Fejes Tóth K, Aravin AA Tags: Trends Genet Source Type: research

Gene Therapy with the Sleeping Beauty Transposon System.
ics Z Abstract The widespread clinical implementation of gene therapy requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective, and economical manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient nonviral gene delivery approaches that are prevalent in ongoing clinical trials. The SB system enables high-level stable gene transfer and sustained transgene expression in multiple primary human somatic cell types, thereby representi...
Source: Trends in Genetics : TIG - September 27, 2017 Category: Genetics & Stem Cells Authors: Kebriaei P, Izsvák Z, Narayanavari SA, Singh H, Ivics Z Tags: Trends Genet Source Type: research

Revisiting the Relationship between Transposable Elements and the Eukaryotic Stress Response.
acute;lez J Abstract A relationship between transposable elements (TEs) and the eukaryotic stress response was suggested in the first publications describing TEs. Since then, it has often been assumed that TEs are activated by stress, and that this activation is often beneficial for the organism. In recent years, the availability of new high-throughput experimental techniques has allowed further interrogation of the relationship between TEs and stress. By reviewing the recent literature, we conclude that although there is evidence for a beneficial effect of TE activation under stress conditions, the relationship b...
Source: Trends in Genetics : TIG - September 22, 2017 Category: Genetics & Stem Cells Authors: Horváth V, Merenciano M, González J Tags: Trends Genet Source Type: research

Stay Connected: A Germ Cell Strategy.
Abstract Germ cells develop as a cyst of interconnected sibling cells in a broad range of organisms in both sexes. A well-established function of intercellular connectivity is to transport cytoplasmic materials from 'nurse' cells to oocytes, a critical process for developing functional oocytes in ovaries of many species. However, there are situations where connectivity exists without a nursing mechanism, and the biological meaning of such connectivity remains obscure. In this review, we summarize current knowledge on the formation of intercellular connectivity, and discuss its meaning by visiting multiple examples...
Source: Trends in Genetics : TIG - September 22, 2017 Category: Genetics & Stem Cells Authors: Lu K, Jensen L, Lei L, Yamashita YM Tags: Trends Genet Source Type: research

The Role of KRAB-ZFPs in Transposable Element Repression and Mammalian Evolution.
Abstract Kruppel-associated box zinc-finger proteins (KRAB-ZFPs) make up the largest family of transcription factors in humans. These proteins emerged in the last common ancestor of coelacanth and tetrapods, and have expanded and diversified in the mammalian lineage. Although their mechanism of transcriptional repression has been well studied for over a decade, the DNA-binding activities and the biological functions of these proteins have been largely unexplored. Recent large-scale ChIP-seq studies and loss-of-function experiments have revealed that KRAB-ZFPs play a major role in the recognition and transcriptiona...
Source: Trends in Genetics : TIG - September 18, 2017 Category: Genetics & Stem Cells Authors: Yang P, Wang Y, Macfarlan TS Tags: Trends Genet Source Type: research

Epithelial-to-Mesenchymal Transition: Epigenetic Reprogramming Driving Cellular Plasticity.
Abstract Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells lose their junctions and polarity to gain a motile mesenchymal phenotype. EMT is essential during embryogenesis and adult physiological processes like wound healing, but is aberrantly activated in pathological conditions like fibrosis and cancer. A series of transcription factors (EMT-inducing transcription factor; EMT-TF) regulate the induction of EMT by repressing the transcription of epithelial genes while activating mesenchymal genes through mechanisms still debated. The nuclear interaction of EMT-TFs with larger protein...
Source: Trends in Genetics : TIG - September 14, 2017 Category: Genetics & Stem Cells Authors: Skrypek N, Goossens S, De Smedt E, Vandamme N, Berx G Tags: Trends Genet Source Type: research

Playing Well with Others: Extrinsic Cues Regulate Neural Progenitor Temporal Identity to Generate Neuronal Diversity.
Abstract During neurogenesis, vertebrate and Drosophila progenitors change over time as they generate a diverse population of neurons and glia. Vertebrate neural progenitors have long been known to use both progenitor-intrinsic and progenitor-extrinsic cues to regulate temporal patterning. In contrast, virtually all temporal patterning mechanisms discovered in Drosophila neural progenitors (neuroblasts) involve progenitor-intrinsic temporal transcription factor cascades. Recent results, however, have revealed several extrinsic pathways that regulate Drosophila neuroblast temporal patterning: nutritional cues regul...
Source: Trends in Genetics : TIG - September 9, 2017 Category: Genetics & Stem Cells Authors: Syed MH, Mark B, Doe CQ Tags: Trends Genet Source Type: research

Transposons As Tools for Functional Genomics in Vertebrate Models.
Abstract Genetic tools and mutagenesis strategies based on transposable elements are currently under development with a vision to link primary DNA sequence information to gene functions in vertebrate models. By virtue of their inherent capacity to insert into DNA, transposons can be developed into powerful tools for chromosomal manipulations. Transposon-based forward mutagenesis screens have numerous advantages including high throughput, easy identification of mutated alleles, and providing insight into genetic networks and pathways based on phenotypes. For example, the Sleeping Beauty transposon has become highly...
Source: Trends in Genetics : TIG - September 6, 2017 Category: Genetics & Stem Cells Authors: Kawakami K, Largaespada DA, Ivics Z Tags: Trends Genet Source Type: research

Beyond Read-Counts: Ribo-seq Data Analysis to Understand the Functions of the Transcriptome.
Abstract By mapping the positions of millions of translating ribosomes in the cell, ribosome profiling (Ribo-seq) has established its role as a powerful tool to study gene expression. Several laboratories have introduced modifications to the experimental protocol and expanded the repertoire of biochemical methods to study translation transcriptome-wide. However, the diversity of protocols highlights a need for standardization. At the same time, different computational analysis strategies have used Ribo-seq data to identify the set of translated sequences with high confidence. In this review we present an overview ...
Source: Trends in Genetics : TIG - September 5, 2017 Category: Genetics & Stem Cells Authors: Calviello L, Ohler U Tags: Trends Genet Source Type: research

The New RNA World: Growing Evidence for Long Noncoding RNA Functionality.
Abstract The past decade has seen a major increase in the study of noncoding RNAs (ncRNAs). However, there remains a great deal of confusion and debate over the levels of functionality and mechanisms of action of the majority of these new transcripts. This Opinion article addresses several of these issues, focusing particularly on long ncRNAs (lncRNAs). We reemphasize the unique abilities of RNAs to form myriad structures as well as to interact with other RNAs, DNA, and proteins, which provide them with unique and powerful abilities. One of these, the ability to interact sequence specifically with DNA, has been la...
Source: Trends in Genetics : TIG - September 1, 2017 Category: Genetics & Stem Cells Authors: Jandura A, Krause HM Tags: Trends Genet Source Type: research

Molecular Dependency Impacts on the Compensating Ability of Paralogs.
PMID: 28870654 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 1, 2017 Category: Genetics & Stem Cells Authors: Landry CR, Diss G Tags: Trends Genet Source Type: research

Birth and Death of Histone mRNAs.
Abstract In metazoans, histone mRNAs are not polyadenylated but end in a conserved stem-loop. Stem-loop binding protein (SLBP) binds to the stem-loop and is required for all steps in histone mRNA metabolism. The genes for the five histone proteins are linked. A histone locus body (HLB) forms at each histone gene locus. It contains factors essential for transcription and processing of histone mRNAs, and couples transcription and processing. The active form of U7 snRNP contains the HLB component FLASH (FLICE-associated huge protein), the histone cleavage complex (HCC), and a subset of polyadenylation factors includi...
Source: Trends in Genetics : TIG - August 31, 2017 Category: Genetics & Stem Cells Authors: Marzluff WF, Koreski KP Tags: Trends Genet Source Type: research

Signaling and Gene Regulatory Networks in Mammalian Lens Development.
Abstract Ocular lens development represents an advantageous system in which to study regulatory mechanisms governing cell fate decisions, extracellular signaling, cell and tissue organization, and the underlying gene regulatory networks. Spatiotemporally regulated domains of BMP, FGF, and other signaling molecules in late gastrula-early neurula stage embryos generate the border region between the neural plate and non-neural ectoderm from which multiple cell types, including lens progenitor cells, emerge and undergo initial tissue formation. Extracellular signaling and DNA-binding transcription factors govern lens ...
Source: Trends in Genetics : TIG - August 31, 2017 Category: Genetics & Stem Cells Authors: Cvekl A, Zhang X Tags: Trends Genet Source Type: research

Regulatory Logic Underlying Diversification of the Neural Crest.
Abstract The neural crest is a transient, multipotent population of cells that arises at the border of the developing nervous system. After closure of the neural tube, these cells undergo an epithelial-to-mesenchymal transition (EMT) to delaminate and migrate, often to distant locations in the embryo. Neural crest cells give rise to a diverse array of derivatives including neurons and glia of the peripheral nervous system, melanocytes, and bone and cartilage of the face. A gene regulatory network (GRN) controls the specification, delamination, migration, and differentiation of this fascinating cell type. With incr...
Source: Trends in Genetics : TIG - August 26, 2017 Category: Genetics & Stem Cells Authors: Martik ML, Bronner ME Tags: Trends Genet Source Type: research

Transposable Element Domestication As an Adaptation to Evolutionary Conflicts.
e;n E Abstract Transposable elements (TEs) are selfish genetic units that typically encode proteins that enable their proliferation in the genome and spread across individual hosts. Here we review a growing number of studies that suggest that TE proteins have often been co-opted or 'domesticated' by their host as adaptations to a variety of evolutionary conflicts. In particular, TE-derived proteins have been recurrently repurposed as part of defense systems that protect prokaryotes and eukaryotes against the proliferation of infectious or invasive agents, including viruses and TEs themselves. We argue that the dom...
Source: Trends in Genetics : TIG - August 24, 2017 Category: Genetics & Stem Cells Authors: Jangam D, Feschotte C, Betrán E Tags: Trends Genet Source Type: research

Circadian Clocks and Metabolism: Implications for Microbiome and Aging.
Abstract The circadian clock directs many aspects of metabolism, to separate in time opposing metabolic pathways and optimize metabolic efficiency. The master circadian clock of the suprachiasmatic nucleus synchronizes to light, while environmental cues such as temperature and feeding, out of phase with the light schedule, may synchronize peripheral clocks. This misalignment of central and peripheral clocks may be involved in the development of disease and the acceleration of aging, possibly in a gender-specific manner. Here we discuss the interplay between the circadian clock and metabolism, the importance of the...
Source: Trends in Genetics : TIG - August 24, 2017 Category: Genetics & Stem Cells Authors: Paschos GK, FitzGerald GA Tags: Trends Genet Source Type: research

Multifarious Functions of the Fragile X Mental Retardation Protein.
Abstract Fragile X syndrome (FXS), a heritable intellectual and autism spectrum disorder (ASD), results from the loss of Fragile X mental retardation protein (FMRP). This neurodevelopmental disease state exhibits neural circuit hyperconnectivity and hyperexcitability. Canonically, FMRP functions as an mRNA-binding translation suppressor, but recent findings have enormously expanded its proposed roles. Although connections between burgeoning FMRP functions remain unknown, recent advances have extended understanding of its involvement in RNA, channel, and protein binding that modulate calcium signaling, activity-dep...
Source: Trends in Genetics : TIG - August 18, 2017 Category: Genetics & Stem Cells Authors: Davis JK, Broadie K Tags: Trends Genet Source Type: research

Gene Duplicates: Agents of Fragility? - A Reply to Landry and Diss.
PMID: 28823576 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - August 17, 2017 Category: Genetics & Stem Cells Authors: Veitia RA Tags: Trends Genet Source Type: research

Mobile Group II Introns as Ancestral Eukaryotic Elements.
Abstract The duality of group II introns, capable of carrying out both self-splicing and retromobility reactions, is hypothesized to have played a profound role in the evolution of eukaryotes. These introns likely provided the framework for the emergence of eukaryotic retroelements, spliceosomal introns and other key components of the spliceosome. Group II introns are found in all three domains of life and are therefore considered to be exceptionally successful mobile genetic elements. Initially identified in organellar genomes, group II introns are found in bacteria, chloroplasts, and mitochondria of plants and f...
Source: Trends in Genetics : TIG - August 14, 2017 Category: Genetics & Stem Cells Authors: Novikova O, Belfort M Tags: Trends Genet Source Type: research

Aneuploidy Police Detect Chromosomal Imbalance Triggering Immune Crackdown!
Abstract Aneuploidy is ubiquitous in cancer and plays a pivotal, early role in tumor evolution. It must therefore be avoided, and two recent papers highlight the roles of p53, senescence, and the immune system in preventing the outgrowth of aneuploid clones in tissue culture. These mechanisms are likely to synergize to maintain diploid cell populations. PMID: 28800914 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - August 8, 2017 Category: Genetics & Stem Cells Authors: Watson EV, Elledge SJ Tags: Trends Genet Source Type: research

Transposable Elements Direct The Coevolution between Plants and Microbes.
Abstract Transposable elements are powerful drivers of genome evolution in many eukaryotes. Although they are mostly considered as 'selfish' genetic elements, increasing evidence suggests that they contribute to genetic variability; particularly under stress conditions. Over the past few years, the role of transposable elements during host-microbe interactions has been recognised. It has been proposed that many pathogenic microbes have evolved a 'two-speed' genome with regions that show increased variability and that are enriched in transposable elements and pathogenicity-related genes. Plants similarly display st...
Source: Trends in Genetics : TIG - August 8, 2017 Category: Genetics & Stem Cells Authors: Seidl MF, Thomma BPHJ Tags: Trends Genet Source Type: research

L1 Mosaicism in Mammals: Extent, Effects, and Evolution.
Abstract The retrotransposon LINE-1 (long interspersed element 1, L1) is a transposable element that has extensively colonized the mammalian germline. L1 retrotransposition can also occur in somatic cells, causing genomic mosaicism, as well as in cancer. However, the extent of L1-driven mosaicism arising during ontogenesis is unclear. We discuss here recent experimental data which, at a minimum, fully substantiate L1 mosaicism in early embryonic development and neural cells, including post-mitotic neurons. We also consider the possible biological impact of somatic L1 insertions in neurons, the existence of donor L...
Source: Trends in Genetics : TIG - August 7, 2017 Category: Genetics & Stem Cells Authors: Faulkner GJ, Garcia-Perez JL Tags: Trends Genet Source Type: research

Speech and Language: Translating the Genome.
Abstract Investigation of the biological basis of human speech and language is being transformed by developments in molecular technologies, including high-throughput genotyping and next-generation sequencing of whole genomes. These advances are shedding new light on the genetic architecture underlying language-related disorders (speech apraxia, specific language impairment, developmental dyslexia) as well as that contributing to variation in relevant skills in the general population. We discuss how state-of-the-art methods are uncovering a range of genetic mechanisms, from rare mutations of large effect to common ...
Source: Trends in Genetics : TIG - August 3, 2017 Category: Genetics & Stem Cells Authors: Deriziotis P, Fisher SE Tags: Trends Genet Source Type: research

On the Origin of lncRNAs: Missing Link Found.
Abstract Non-coding (nc)RNAs known as enhancer-derived RNAs (eRNAs) and as long ncRNAs (lncRNAs) have received much attention, but their true functional specialization and evolutionary origins remain obscure. The recent characterization of Bloodlinc, an eRNA derived from a super-enhancer that also functions as a lncRNA, suggests that lncRNAs can evolve from eRNAs. PMID: 28778681 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - August 1, 2017 Category: Genetics & Stem Cells Authors: Espinosa JM Tags: Trends Genet Source Type: research

CRISPRing the Regulatory Genome, the Challenge Ahead.
Abstract CRISPR saturation mutagenesis has the potential to dissect the functional landscape of noncoding regions, but is highly susceptible to false discovery and misinterpretation. As recently published, Canver et al. have now taken the first steps towards addressing these issues by increasing screening resolution and analyzing the effects of off targets on hit calling. PMID: 28764860 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - July 29, 2017 Category: Genetics & Stem Cells Authors: Sansbury SE, Sweeney KM, Shalem O Tags: Trends Genet Source Type: research

Clinical Genomics in Inflammatory Bowel Disease.
Abstract Genomic technologies inform the complex genetic basis of polygenic inflammatory bowel disease (IBD) as well as Mendelian disease-associated IBD. Aiming to diagnose patients that present with extreme phenotypes due to monogenic forms of IBD, genomics has progressed from 'orphan disease' research towards an integrated standard of clinical care. Advances in diagnostic clinical genomics are increasingly complemented by pathway-specific therapies that aim to correct the consequences of genetic defects. This highlights the exceptional potential for personalized precision medicine. IBD is nevertheless a challeng...
Source: Trends in Genetics : TIG - July 26, 2017 Category: Genetics & Stem Cells Authors: Uhlig HH, Muise AM Tags: Trends Genet Source Type: research

High-Throughput Imaging for the Discovery of Cellular Mechanisms of Disease.
Abstract High-throughput imaging (HTI) is a powerful tool in the discovery of cellular disease mechanisms. While traditional approaches to identify disease pathways often rely on knowledge of the causative genetic defect, HTI-based screens offer an unbiased discovery approach based on any morphological or functional defects of disease cells or tissues. In this review, we provide an overview of the use of HTI for the study of human disease mechanisms. We discuss key technical aspects of HTI and highlight representative examples of its practical applications for the discovery of molecular mechanisms of disease, focu...
Source: Trends in Genetics : TIG - July 18, 2017 Category: Genetics & Stem Cells Authors: Pegoraro G, Misteli T Tags: Trends Genet Source Type: research

Evolutionary Dynamics of Unreduced Gametes.
Abstract Unreduced gametes, which have the somatic (2n) chromosome number, are an important precursor to polyploid formation and apomixis. The product of irregularities in meiosis, 2n gametes are expected to be rare and deleterious in most natural populations, contrary to their wide taxonomic distribution and the prevalence of polyploidy. To better understand this discrepancy, we review contemporary evidence related to four aspects of 2n gamete dynamics in natural populations: (i) estimates of their frequency; (ii) their environmental and genetic determinants; (iii) adaptive and nonadaptive processes regulating th...
Source: Trends in Genetics : TIG - July 18, 2017 Category: Genetics & Stem Cells Authors: Kreiner JM, Kron P, Husband BC Tags: Trends Genet Source Type: research

Time to Go Bigger: Emerging Patterns in Macrogenetics.
Abstract The increasing availability of large-scale and high-resolution data sets in population genetics is moving the field toward a novel research agenda. Here, we show how this shift toward macrogenetics should generate new perspectives and theories allowing the description, understanding, and prediction of patterns of genetic diversity at broad spatial, temporal, and taxonomic scales. PMID: 28720482 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - July 15, 2017 Category: Genetics & Stem Cells Authors: Blanchet S, Prunier JG, De Kort H Tags: Trends Genet Source Type: research

Left-Right Patterning: Breaking Symmetry to Asymmetric Morphogenesis.
Abstract Vertebrates exhibit striking left-right (L-R) asymmetries in the structure and position of the internal organs. Symmetry is broken by motile cilia-generated asymmetric fluid flow, resulting in a signaling cascade - the Nodal-Pitx2 pathway - being robustly established within mesodermal tissue on the left side only. This pathway impinges upon various organ primordia to instruct their side-specific development. Recently, progress has been made in understanding both the breaking of embryonic L-R symmetry and how the Nodal-Pitx2 pathway controls lateralized cell differentiation, migration, and other aspects of...
Source: Trends in Genetics : TIG - July 15, 2017 Category: Genetics & Stem Cells Authors: Grimes DT, Burdine RD Tags: Trends Genet Source Type: research

Roles of RNase P and Its Subunits.
Abstract Recent studies show that nuclear RNase P is linked to chromatin structure and function. Thus, variants of this ribonucleoprotein (RNP) complex bind to chromatin of small noncoding RNA genes; integrate into initiation complexes of RNA polymerase (Pol) III; repress histone H3.3 nucleosome deposition; control tRNA and PIWI-interacting RNA (piRNA) gene clusters for genome defense; and respond to Werner syndrome helicase (WRN)-related replication stress and DNA double-strand breaks (DSBs). Likewise, the related RNase MRP and RMRP-TERT (telomerase reverse transcriptase) are implicated in RNA-dependent RNA polym...
Source: Trends in Genetics : TIG - July 8, 2017 Category: Genetics & Stem Cells Authors: Jarrous N Tags: Trends Genet Source Type: research

Genome-wide Mapping of the Nucleosome Landscape by Micrococcal Nuclease and Chemical Mapping.
Abstract Nucleosomes regulate the transcription output of the genome by occluding the underlying DNA sequences from DNA-binding proteins that must act on it. Knowledge of the precise locations of nucleosomes in the genome is thus essential towards understanding how transcription is regulated. Current nucleosome-mapping strategies involve digesting chromatin with nucleases or chemical cleavage followed by high-throughput sequencing. In this review, we compare the traditional micrococcal nuclease (MNase)-based approach with a chemical cleavage strategy, with discussion on the important insights each has uncovered ab...
Source: Trends in Genetics : TIG - July 7, 2017 Category: Genetics & Stem Cells Authors: Voong LN, Xi L, Wang JP, Wang X Tags: Trends Genet Source Type: research

Mining Metagenomic Data Sets for Ancient DNA: Recommended Protocols for Authentication.
Abstract While a comparatively young area of research, investigations relying on ancient DNA data have been highly valuable in revealing snapshots of genetic variation in both the recent and the not-so-recent past. Born out of a tradition of single-locus PCR-based approaches that often target individual species, stringent criteria for both data acquisition and analysis were introduced early to establish high standards of data quality. Today, the immense volume of data made available through next-generation sequencing has significantly increased the analytical resolution offered by processing ancient tissues and pe...
Source: Trends in Genetics : TIG - July 5, 2017 Category: Genetics & Stem Cells Authors: Key FM, Posth C, Krause J, Herbig A, Bos KI Tags: Trends Genet Source Type: research

Histone H2A Monoubiquitination in Neurodevelopmental Disorders.
Abstract Covalent histone modifications play an essential role in gene regulation and cellular specification required for multicellular organism development. Monoubiquitination of histone H2A (H2AUb1) is a reversible transcriptionally repressive mark. Exchange of histone H2A monoubiquitination and deubiquitination reflects the succession of transcriptional profiles during development required to produce cellular diversity from pluripotent cells. Germ-line pathogenic variants in components of the H2AUb1 regulatory axis are being identified as the genetic basis of congenital neurodevelopmental disorders. Here, we re...
Source: Trends in Genetics : TIG - June 29, 2017 Category: Genetics & Stem Cells Authors: Srivastava A, McGrath B, Bielas SL Tags: Trends Genet Source Type: research

Driving to Cancer on a Four-Lane Expressway.
Abstract Recent findings from a prospective clinical study involving multiregion whole-exome sequencing suggest that driver mutations in cancer-relevant genes including EGFR and TP53 are often clonal and precede whole-genome duplication events in early lung carcinogenesis. This paves an expressway to extensive subclonal diversification, elevated intratumoral heterogeneity, and dismal disease outcome. PMID: 28668385 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - June 28, 2017 Category: Genetics & Stem Cells Authors: Galluzzi L, Vitale I Tags: Trends Genet Source Type: research

Advances in Decoding Axolotl Limb Regeneration.
Abstract Humans and other mammals are limited in their natural abilities to regenerate lost body parts. By contrast, many salamanders are highly regenerative and can spontaneously replace lost limbs even as adults. Because salamander limbs are anatomically similar to human limbs, knowing how they regenerate should provide important clues for regenerative medicine. Although interest in understanding the mechanics of this process has never wavered, until recently researchers have been vexed by seemingly impenetrable logistics of working with these creatures at a molecular level. Chief among the problems has been the...
Source: Trends in Genetics : TIG - June 22, 2017 Category: Genetics & Stem Cells Authors: Haas BJ, Whited JL Tags: Trends Genet Source Type: research

Uncovering Gene Regulatory Networks Controlling Plant Cell Differentiation.
Abstract The development of multicellular organisms relies on the precise regulation of cellular differentiation. As such, there has been significant effort invested to understand the process through which an immature cell undergoes differentiation. In this review, we highlight key discoveries and advances that have contributed to our understanding of the transcriptional networks underlying Arabidopsis root endodermal differentiation. To conclude, we propose perspectives on how advances in molecular biology, microscopy, and nucleotide sequencing will provide the tools to test the biological significance of these g...
Source: Trends in Genetics : TIG - June 21, 2017 Category: Genetics & Stem Cells Authors: Drapek C, Sparks EE, Benfey PN Tags: Trends Genet Source Type: research

The Genes That Make a Good Parent.
Abstract What is the genetic basis of differences in parental care between promiscuous and monogamous mammal species? A team led by Hopi Hoekstra studied an intercross between deer mice and old-field mice that differ in their mating systems and parental behaviours. The authors discovered 12 genomic regions contributing to those differences and identified vasopressin as a regulator of nestbuilding behaviour. PMID: 28633980 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - June 17, 2017 Category: Genetics & Stem Cells Authors: Hager R Tags: Trends Genet Source Type: research

The Diversity of Long Noncoding RNAs and Their Generation.
Abstract Long noncoding RNAs (lncRNAs) are emerging as potential key regulators in gene expression networks and exhibit a surprising range of shapes and sizes. Several distinct classes of lncRNAs are transcribed from different DNA elements, including promoters, enhancers, and intergenic regions in eukaryotic genomes. Additionally, others are derived from long primary transcripts with noncanonical RNA processing pathways, generating new RNA species with unexpected formats. These lncRNAs can be processed by several mechanisms, including ribonuclease P (RNase P) cleavage to generate mature 3' ends, capping by small n...
Source: Trends in Genetics : TIG - June 16, 2017 Category: Genetics & Stem Cells Authors: Wu H, Yang L, Chen LL Tags: Trends Genet Source Type: research

Antibiotic-Independent Adaptive Effects of Antibiotic Resistance Mutations.
Abstract Antibiotic usage selects for the accumulation and spread of antibiotic-resistant bacteria. However, resistance can also accumulate in the absence of antibiotic exposure. Antibiotics are often designed to target widely distributed regulatory housekeeping genes. The targeting of such genes enables these antibiotics to be useful against a wider variety of pathogens. This review highlights work suggesting that regulatory housekeeping genes of the type targeted by many antibiotics function as hubs of adaptation to conditions unrelated to antibiotic exposure. As a result of this, some mutations to the regulator...
Source: Trends in Genetics : TIG - June 16, 2017 Category: Genetics & Stem Cells Authors: Hershberg R Tags: Trends Genet Source Type: research

A Fundamental Unit of Cell Size in Bacteria.
Abstract A new study clarifies a relationship between growth, gene expression, and cell size in cyanobacteria. Quite unexpectedly, cyanobacteria and Escherichia coli appear to share an invariance principle to coordinate growth and chromosome replication. This principle allows quantitative predictions of cell size across a range of growth conditions in both organisms. PMID: 28545962 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - May 22, 2017 Category: Genetics & Stem Cells Authors: Jun S, Rust MJ Tags: Trends Genet Source Type: research

The Dimensions, Dynamics, and Relevance of the Mammalian Noncoding Transcriptome.
We describe here the key studies and technological advances that have shaped our understanding of the dimensions, dynamics, and biological relevance of the mammalian noncoding transcriptome. PMID: 28535931 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - May 20, 2017 Category: Genetics & Stem Cells Authors: Deveson IW, Hardwick SA, Mercer TR, Mattick JS Tags: Trends Genet Source Type: research

V(D)J Recombination Exploits DNA Damage Responses to Promote Immunity.
Abstract It has been recognized for 40 years that the variable (diversity) joining [V(D)J] recombination-mediated assembly of diverse B and T lymphocyte antigen receptor (AgR) genes is not only essential for adaptive immunity, but also a risk for autoimmunity and lymphoid malignancies. Over the past few years, several studies have revealed that recombination-activating gene (RAG) endonuclease-induced DNA double-strand breaks (DSBs) transcend hazardous intermediates during antigen receptor gene assembly. RAG cleavage within the genomes of lymphocyte progenitors and immature lymphocytes regulates the expression of u...
Source: Trends in Genetics : TIG - May 19, 2017 Category: Genetics & Stem Cells Authors: Arya R, Bassing CH Tags: Trends Genet Source Type: research

Perspectives on Gene Regulatory Network Evolution.
Abstract Animal development proceeds through the activity of genes and their cis-regulatory modules (CRMs) working together in sets of gene regulatory networks (GRNs). The emergence of species-specific traits and novel structures results from evolutionary changes in GRNs. Recent work in a wide variety of animal models, and particularly in insects, has started to reveal the modes and mechanisms of GRN evolution. I discuss here various aspects of GRN evolution and argue that developmental system drift (DSD), in which conserved phenotype is nevertheless a result of changed genetic interactions, should regularly be vi...
Source: Trends in Genetics : TIG - May 18, 2017 Category: Genetics & Stem Cells Authors: Halfon MS Tags: Trends Genet Source Type: research

Sociomics: Using Omic Approaches to Understand Social Evolution.
Abstract All of life is social, from genes cooperating to form organisms, to animals cooperating to form societies. Omic approaches offer exceptional opportunities to solve major outstanding problems in the study of how sociality evolves. First, omics can be used to clarify the extent and form of sociality in natural populations. This is especially useful in species where it is difficult to study social traits in natural populations, such as bacteria and other microbes. Second, omics can be used to examine the consequences of sociality for genome evolution and gene expression. This is especially useful in cases wh...
Source: Trends in Genetics : TIG - May 12, 2017 Category: Genetics & Stem Cells Authors: Ghoul M, Andersen SB, West SA Tags: Trends Genet Source Type: research