Beyond Promoters: How Genes Tweak Their Own Expression
Publication date: Available online 14 August 2018Source: Trends in GeneticsAuthor(s): Tamás Székely, Gábor BalázsiThe correct expression of genes is vital for cells to function. Schikora-Tamarit et al. show that, in addition to obeying their promoters, most genes can modulate their own expression by either buffering or amplification. This could help to avoid costly overexpression of proteins. (Source: Trends in Genetics)
Source: Trends in Genetics - August 15, 2018 Category: Genetics & Stem Cells Source Type: research

Editorial Board and Contents
Publication date: September 2018Source: Trends in Genetics, Volume 34, Issue 9Author(s): (Source: Trends in Genetics)
Source: Trends in Genetics - August 14, 2018 Category: Genetics & Stem Cells Source Type: research

Spermatogenesis and the Evolution of Mammalian Sex Chromosomes
Publication date: Available online 1 August 2018Source: Trends in GeneticsAuthor(s): Erica L. Larson, Emily E.K. Kopania, Jeffrey M. GoodDevelopmental constraint and sexual conflict shape the evolution of heteromorphic sex chromosomes. These contrasting forces are perhaps strongest during spermatogenesis in species with XY males. In this review, we consider how the unique regulatory environment and selective pressures of spermatogenesis interact to impact sex chromosome evolution in mammals. We explore how each developmental phase of spermatogenesis influences sex chromosome gene content, structure, and rate of molecular e...
Source: Trends in Genetics - August 2, 2018 Category: Genetics & Stem Cells Source Type: research

Nimble and Ready to Mingle: Transposon Outbursts of Early Development
Publication date: Available online 26 July 2018Source: Trends in GeneticsAuthor(s): Diego Rodriguez-Terrones, Maria-Elena Torres-PadillaTransposable elements are the largest individual constituent of mammalian genomes. These elements are highly diverse, a consequence of the multiplicity of genomic habitats that they inhabit and of the complex evolutionary histories that they have developed therein. Intriguingly, a surge of transposable element transcription occurs during mammalian preimplantation development, contributing to the establishment of totipotency and pluripotency and to the activation of the embryonic genome. Ho...
Source: Trends in Genetics - July 27, 2018 Category: Genetics & Stem Cells Source Type: research

New and Prospective Roles for lncRNAs in Organelle Formation and Function
Publication date: Available online 17 July 2018Source: Trends in GeneticsAuthor(s): Henry M. KrauseThe observation that long noncoding RNAs (lncRNAs) represent the majority of transcripts in humans has led to a rapid increase in interest and study. Most of this interest has focused on their roles in the nucleus. However, increasing evidence is beginning to reveal even more functions outside the nucleus, and even outside cells. Many of these roles are mediated by newly discovered properties, including the ability of lncRNAs to interact with lipids, membranes, and disordered protein domains, and to form differentially solubl...
Source: Trends in Genetics - July 18, 2018 Category: Genetics & Stem Cells Source Type: research

Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls
Publication date: Available online 17 July 2018Source: Trends in GeneticsAuthor(s): Huifen Cao, Claes Wahlestedt, Philipp KapranovThe past decade has seen an explosion of interest in long noncoding RNAs (lncRNAs). However, despite the massive volume of scientific data implicating these transcripts in a plethora of molecular and cellular processes, a great deal of controversy surrounds these RNAs. One of the main reasons for this lies in the multiple unique features of lncRNAs which limit the available methods used to characterize them. Combined with their vast numbers and inadequate classification, comprehensive annotation...
Source: Trends in Genetics - July 18, 2018 Category: Genetics & Stem Cells Source Type: research

Experimental Studies of Evolutionary Dynamics in Microbes
Publication date: Available online 17 July 2018Source: Trends in GeneticsAuthor(s): Ivana Cvijović, Alex N. Nguyen Ba, Michael M. DesaiEvolutionary dynamics in laboratory microbial evolution experiments can be surprisingly complex. In the past two decades, observations of these dynamics have challenged simple models of adaptation and have shown that clonal interference, hitchhiking, ecological diversification, and contingency are widespread. In recent years, advances in high-throughput strain maintenance and phenotypic assays, the dramatically reduced cost of genome sequencing, and emerging methods for lineage barcoding h...
Source: Trends in Genetics - July 17, 2018 Category: Genetics & Stem Cells Source Type: research

Editorial Board and Contents
Publication date: August 2018Source: Trends in Genetics, Volume 34, Issue 8Author(s): (Source: Trends in Genetics)
Source: Trends in Genetics - July 17, 2018 Category: Genetics & Stem Cells Source Type: research

Single-Cell Multi-omics: An Engine for New Quantitative Models of Gene Regulation
Publication date: Available online 11 July 2018Source: Trends in GeneticsAuthor(s): Jonathan Packer, Cole TrapnellCells in a multicellular organism fulfill specific functions by enacting cell-type-specific programs of gene regulation. Single-cell RNA sequencing technologies have provided a transformative view of cell-type-specific gene expression, the output of cell-type-specific gene regulatory programs. This review discusses new single-cell genomic technologies that complement single-cell RNA sequencing by providing additional readouts of cellular state beyond the transcriptome. We highlight regression models as a simple...
Source: Trends in Genetics - July 12, 2018 Category: Genetics & Stem Cells Source Type: research

Long-Distance Relationships: Suppression of Repeat-Mediated Deletions
Publication date: Available online 24 May 2018Source: Trends in GeneticsAuthor(s): Maria E. Morales, Tiffany Kaul, Prescott DeiningerThe high proportion of repetitive DNA sequences in the human genome provides tremendous opportunities for DNA rearrangements between non-allelic repetitive elements. The genome must use multiple competing and collaborating repair mechanisms to minimize these types of DNA rearrangements, some of which fail in cancer cells where DNA repair pathways are suppressed. (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Rad5, HLTF, and SHPRH: A Fresh View of an Old Story
Publication date: Available online 26 May 2018Source: Trends in GeneticsAuthor(s): Menattallah Elserafy, Arwa A. Abugable, Reham Atteya, Sherif F. El-KhamisyNot only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches. (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

DNA Modifications: Naturally More Error Prone?
Publication date: Available online 28 May 2018Source: Trends in GeneticsAuthor(s): Marketa Tomkova, Benjamin Schuster-BöcklerEpigenetic DNA modifications are essential for normal cell function in vertebrates, but they can also be hotspots of mutagenesis. Methylcytosine in particular has long been known to be less stable than other nucleotides and spontaneously deaminates to thymine. Beyond this well-established phenomenon, however, the influence of epigenetic marks on mutagenesis has recently become an active field of investigation. In this review, we summarize current knowledge of the interactions between different D...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Comparing Apples to Apples and Oranges to Oranges
Publication date: Available online 28 May 2018Source: Trends in GeneticsAuthor(s): Guillaume BourqueA new study sequenced and assembled two rodent genomes to better understand the evolutionary forces shaping mammalian genomes. Their results suggest multiple roles for genomic repeats. (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Reflections of a Biomedical Scientist on Four Continents in Interdisciplinary Research
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Juergen K.V. Reichardt (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

ALS Genes in the Genomic Era and their Implications for FTD
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Hung Phuoc Nguyen, Christine Van Broeckhoven, Julie van der ZeeAmyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient–control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Genetic Villains: Killer Meiotic Drivers
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): María Angélica Bravo Núñez, Nicole L. Nuckolls, Sarah E. ZandersUnbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel’s Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic pr...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Understanding Alzheimer Disease at the Interface between Genetics and Transcriptomics
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Jan Verheijen, Kristel SleegersOver 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics,...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Ryan J. McGinty, Sergei M. MirkinOver 30 hereditary diseases are caused by the expansion of microsatellite repeats. The length of the expandable repeat is the main hereditary determinant of these disorders. They are also affected by numerous genomic variants that are either nearby (cis) or physically separated from (trans) the repetitive locus, which we review here. These genetic variants have largely been elucidated in model systems using gene knockouts, while a few have been directly observed as single-nucleotide polymorphisms (SNPs) in p...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Perspectives on Glycosylation and Its Congenital Disorders
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Bobby G. Ng, Hudson H. FreezeCongenital disorders of glycosylation (CDG) are a rapidly expanding group of metabolic disorders that result from abnormal protein or lipid glycosylation. They are often difficult to clinically diagnose because they broadly affect many organs and functions and lack clinical uniformity. However, recent technological advances in next-generation sequencing have revealed a treasure trove of new genetic disorders, expanded the knowledge of known disorders, and showed a critical role in infectious diseases. More compr...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

SMC Complexes: Universal DNA Looping Machines with Distinct Regulators
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Marjon S. van Ruiten, Benjamin D. RowlandWhat drives the formation of chromatin loops has been a long-standing question in chromosome biology. Recent work provides major insight into the basic principles behind loop formation. Structural maintenance of chromosomes (SMC) complexes, that are conserved from bacteria to humans, are key to this process. The SMC family includes condensin and cohesin, which structure chromosomes to enable mitosis and long-range gene regulation. We discuss novel insights into the mechanism of loop formation and the...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Editorial Board and Contents
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Transcribing Centromeres: Noncoding RNAs and Kinetochore Assembly
Publication date: Available online 2 June 2018Source: Trends in GeneticsAuthor(s): Paul B. Talbert, Steven HenikoffChromosome segregation depends on the attachment of spindle microtubules to sites on chromosomal DNA known as centromeres, through kinetochore protein complexes. Although RNA was found in kinetochores in the 1970s, only with recent investigations has evidence emerged that loading of the centromere-specific nucleosomes that form the foundation of the kinetochore may be coupled to centromeric transcription. Centromeric transcripts are bound by several kinetochore proteins that require them for stabilization or l...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Genetic Network Complexity Shapes Background-Dependent Phenotypic Expression
Publication date: Available online 11 June 2018Source: Trends in GeneticsAuthor(s): Jing Hou, Jolanda van Leeuwen, Brenda J. Andrews, Charles BooneThe phenotypic consequences of a given mutation can vary across individuals. This so-called background effect is widely observed, from mutant fitness of loss-of-function variants in model organisms to variable disease penetrance and expressivity in humans; however, the underlying genetic basis often remains unclear. Taking insights gained from recent large-scale surveys of genetic interaction and suppression analyses in yeast, we propose that the genetic network context for a gi...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Harnessing Tumor Evolution to Circumvent Resistance
Publication date: Available online 11 June 2018Source: Trends in GeneticsAuthor(s): Katherine L. Pogrebniak, Christina CurtisHigh-throughput sequencing can be used to measure changes in tumor composition across space and time. Specifically, comparisons of pre- and post-treatment samples can reveal the underlying clonal dynamics and resistance mechanisms. Here, we discuss evidence for distinct modes of tumor evolution and their implications for therapeutic strategies. In addition, we consider the utility of spatial tissue sampling schemes, single-cell analysis, and circulating tumor DNA to track tumor evolution and the emer...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Gene Editing on Center Stage
Publication date: Available online 13 June 2018Source: Trends in GeneticsAuthor(s): Rasmus O. Bak, Natalia Gomez-Ospina, Matthew H. PorteusSmithies et al. (1985) and Jasin and colleagues (1994) provided proof of concept that homologous recombination (HR) could be applied to the treatment of human disease and that its efficiency could be improved by the induction of double-strand breaks (DSBs). A key advance was the discovery of engineered nucleases, such as zinc-finger nucleases (ZFNs) and transcription activator-like (TAL) effector nucleases (TALENs), that can generate site-specific DSBs. The democratization and widesprea...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

P-Bodies: Cytosolic Droplets for Coordinated mRNA Storage
Publication date: Available online 13 June 2018Source: Trends in GeneticsAuthor(s): Nancy Standart, Dominique WeilP-bodies (PBs) are cytosolic RNP granules that are conserved among eukaryotic organisms. In the past few years, major progress has been made in understanding the biochemical and biophysical mechanisms that lead to their formation. However, whether they play a role in mRNA storage or decay remains actively debated. P-bodies were recently isolated from human cells by a novel fluorescence-activated particle sorting (FAPS) approach that enabled the characterization of their protein and RNA content, providing new in...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

The Third Revolution in Sequencing Technology
Publication date: Available online 22 June 2018Source: Trends in GeneticsAuthor(s): Erwin L. van Dijk, Yan Jaszczyszyn, Delphine Naquin, Claude ThermesForty years ago the advent of Sanger sequencing was revolutionary as it allowed complete genome sequences to be deciphered for the first time. A second revolution came when next-generation sequencing (NGS) technologies appeared, which made genome sequencing much cheaper and faster. However, NGS methods have several drawbacks and pitfalls, most notably their short reads. Recently, third-generation/long-read methods appeared, which can produce genome assemblies of unprecedente...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective
Publication date: Available online 23 June 2018Source: Trends in GeneticsAuthor(s): Gilad Barshad, Shani Marom, Tal Cohen, Dan MishmarThe bacterial heritage of mitochondria, as well as its independent genome [mitochondrial DNA (mtDNA)] and polycistronic transcripts, led to the view that mitochondrial transcriptional regulation relies on an evolutionarily conserved, prokaryotic-like system that is separated from the rest of the cell. Indeed, mtDNA transcription was previously thought to be governed by a few dedicated direct regulators, namely, the mitochondrial RNA polymerase (POLRMT), two transcription factors (TFAM and TF...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

The Evolution of Gene Expression in cis and trans
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): Sarah A. Signor, Sergey V. NuzhdinThere is abundant variation in gene expression between individuals, populations, and species. The evolution of gene regulation and expression within and between species is thought to frequently contribute to adaptation. Yet considerable evidence suggests that the primary evolutionary force acting on variation in gene expression is stabilizing selection. We review here the results of recent studies characterizing the evolution of gene expression occurring in cis (via linked polymorphisms) or in trans (throug...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Editorial Board and Contents
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Forensic Epigenetic Age Estimation and Beyond: Ethical and Legal Considerations
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): Mahsa Shabani, Pascal Borry, Inge Smeers, Bram BekaertForensic geneticists are in a race to develop methods based on DNA methylation for various forensic applications, including age estimation. We argue that using epigenetic biomarkers could reveal a broad range of health and life-style related information, therefore it is necessary to develop adequate safeguards to protect the privacy of the individuals under scrutiny. (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Why Do Sex Chromosomes Stop Recombining?
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): Suvi Ponnikas, Hanna Sigeman, Jessica K. Abbott, Bengt HanssonIt is commonly assumed that sex chromosomes evolve recombination suppression because selection favours linkage between sex-determining and sexually antagonistic genes. However, although the role of sexual antagonism during sex chromosome evolution has attained strong support from theory, experimental and observational evidence is rare or equivocal. Here, we highlight alternative, often neglected, hypotheses for recombination suppression on sex chromosomes, which invoke meiotic dr...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Replicability and Prediction: Lessons and Challenges from GWAS
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): Urko M. Marigorta, Juan Antonio Rodríguez, Greg Gibson, Arcadi NavarroSince the publication of the Wellcome Trust Case Control Consortium (WTCCC) landmark study a decade ago, genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in disease etiology. This success story has two angles that are often overlooked. First, GWAS findings are highly replicable. This is an unprecedented phenomenon in complex trait genetics, and indeed in many areas of science, which in past decades have been pl...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Break-Induced Replication: The Where, The Why, and The How
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): J. Kramara, B. Osia, A. MalkovaBreak-induced replication (BIR) is a pathway that repairs one-ended double-strand breaks (DSBs). For decades, yeast model systems offered the only opportunities to study eukaryotic BIR. These studies described an unusual mode of BIR synthesis that is carried out by a migrating bubble and shows conservative inheritance of newly synthesized DNA, leading to genomic instabilities like those associated with cancer in humans. Yet, evidence of BIR functioning in mammals or during repair of other DNA breaks has been m...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Genetic-Driven Druggable Target Identification and Validation
Publication date: July 2018Source: Trends in Genetics, Volume 34, Issue 7Author(s): Matteo Floris, Stefania Olla, David Schlessinger, Francesco CuccaChoosing the right biological target is the critical primary decision for the development of new drugs. Systematic genetic association testing of both human diseases and quantitative traits, along with resultant findings of coincident associations between them, is becoming a powerful approach to infer drug targetable candidates and generate in vitro tests to identify compounds that can modulate them therapeutically. Here, we discuss opportunities and challenges, and infer crit...
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Detecting Somatic Mutations in Normal Cells
We describe here approaches for characterizing somatic mutations in normal and non-tumor disease tissues. We discuss several experimental designs and common pitfalls in somatic mutation detection, as well as more recent developments such as phasing and linked-read technology. With the dramatically increasing numbers of samples undergoing genome sequencing, bioinformatic analysis will enable the characterization of somatic mutations and their impact on non-cancer tissues. (Source: Trends in Genetics)
Source: Trends in Genetics - July 10, 2018 Category: Genetics & Stem Cells Source Type: research

Long-Distance Relationships: Suppression of Repeat-Mediated Deletions
Publication date: Available online 24 May 2018Source: Trends in GeneticsAuthor(s): Maria E. Morales, Tiffany Kaul, Prescott DeiningerThe high proportion of repetitive DNA sequences in the human genome provides tremendous opportunities for DNA rearrangements between non-allelic repetitive elements. The genome must use multiple competing and collaborating repair mechanisms to minimize these types of DNA rearrangements, some of which fail in cancer cells where DNA repair pathways are suppressed. (Source: Trends in Genetics)
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Rad5, HLTF, and SHPRH: A Fresh View of an Old Story
Publication date: Available online 26 May 2018Source: Trends in GeneticsAuthor(s): Menattallah Elserafy, Arwa A. Abugable, Reham Atteya, Sherif F. El-KhamisyNot only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches. (Source: Trends in Genetics)
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

DNA Modifications: Naturally More Error Prone?
Publication date: Available online 28 May 2018Source: Trends in GeneticsAuthor(s): Marketa Tomkova, Benjamin Schuster-BöcklerEpigenetic DNA modifications are essential for normal cell function in vertebrates, but they can also be hotspots of mutagenesis. Methylcytosine in particular has long been known to be less stable than other nucleotides and spontaneously deaminates to thymine. Beyond this well-established phenomenon, however, the influence of epigenetic marks on mutagenesis has recently become an active field of investigation. In this review, we summarize current knowledge of the interactions between different D...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Comparing Apples to Apples and Oranges to Oranges
Publication date: Available online 28 May 2018Source: Trends in GeneticsAuthor(s): Guillaume BourqueA new study sequenced and assembled two rodent genomes to better understand the evolutionary forces shaping mammalian genomes. Their results suggest multiple roles for genomic repeats. (Source: Trends in Genetics)
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Reflections of a Biomedical Scientist on Four Continents in Interdisciplinary Research
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Juergen K.V. Reichardt (Source: Trends in Genetics)
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

ALS Genes in the Genomic Era and their Implications for FTD
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Hung Phuoc Nguyen, Christine Van Broeckhoven, Julie van der ZeeAmyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient–control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Genetic Villains: Killer Meiotic Drivers
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): María Angélica Bravo Núñez, Nicole L. Nuckolls, Sarah E. ZandersUnbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel’s Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic pr...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Understanding Alzheimer Disease at the Interface between Genetics and Transcriptomics
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Jan Verheijen, Kristel SleegersOver 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics,...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Ryan J. McGinty, Sergei M. MirkinOver 30 hereditary diseases are caused by the expansion of microsatellite repeats. The length of the expandable repeat is the main hereditary determinant of these disorders. They are also affected by numerous genomic variants that are either nearby (cis) or physically separated from (trans) the repetitive locus, which we review here. These genetic variants have largely been elucidated in model systems using gene knockouts, while a few have been directly observed as single-nucleotide polymorphisms (SNPs) in p...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Perspectives on Glycosylation and Its Congenital Disorders
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Bobby G. Ng, Hudson H. FreezeCongenital disorders of glycosylation (CDG) are a rapidly expanding group of metabolic disorders that result from abnormal protein or lipid glycosylation. They are often difficult to clinically diagnose because they broadly affect many organs and functions and lack clinical uniformity. However, recent technological advances in next-generation sequencing have revealed a treasure trove of new genetic disorders, expanded the knowledge of known disorders, and showed a critical role in infectious diseases. More compr...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

SMC Complexes: Universal DNA Looping Machines with Distinct Regulators
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): Marjon S. van Ruiten, Benjamin D. RowlandWhat drives the formation of chromatin loops has been a long-standing question in chromosome biology. Recent work provides major insight into the basic principles behind loop formation. Structural maintenance of chromosomes (SMC) complexes, that are conserved from bacteria to humans, are key to this process. The SMC family includes condensin and cohesin, which structure chromosomes to enable mitosis and long-range gene regulation. We discuss novel insights into the mechanism of loop formation and the...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Editorial Board and Contents
Publication date: June 2018Source: Trends in Genetics, Volume 34, Issue 6Author(s): (Source: Trends in Genetics)
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Transcribing Centromeres: Noncoding RNAs and Kinetochore Assembly
Publication date: Available online 2 June 2018Source: Trends in GeneticsAuthor(s): Paul B. Talbert, Steven HenikoffChromosome segregation depends on the attachment of spindle microtubules to sites on chromosomal DNA known as centromeres, through kinetochore protein complexes. Although RNA was found in kinetochores in the 1970s, only with recent investigations has evidence emerged that loading of the centromere-specific nucleosomes that form the foundation of the kinetochore may be coupled to centromeric transcription. Centromeric transcripts are bound by several kinetochore proteins that require them for stabilization or l...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research

Genetic Network Complexity Shapes Background-Dependent Phenotypic Expression
Publication date: Available online 11 June 2018Source: Trends in GeneticsAuthor(s): Jing Hou, Jolanda van Leeuwen, Brenda J. Andrews, Charles BooneThe phenotypic consequences of a given mutation can vary across individuals. This so-called background effect is widely observed, from mutant fitness of loss-of-function variants in model organisms to variable disease penetrance and expressivity in humans; however, the underlying genetic basis often remains unclear. Taking insights gained from recent large-scale surveys of genetic interaction and suppression analyses in yeast, we propose that the genetic network context for a gi...
Source: Trends in Genetics - July 5, 2018 Category: Genetics & Stem Cells Source Type: research