Whole-Genome Duplication and Yeast's Fruitful Way of Life.
lez A Abstract Studies on the fate of Saccharomyces cerevisiae paralogous gene pairs that arose through a whole-genome duplication event have shown diversification of retained duplicated genes. Paralogous functional specialization often results in improved function and/or novel function that could contribute to the adaptation of the organism to a new lifestyle. Here, we analyze and discuss particular case studies of paralogous functional diversification that could have played a role in the acquisition of yeast fermentative metabolism. PMID: 30366621 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - October 23, 2018 Category: Genetics & Stem Cells Authors: Escalera-Fanjul X, Quezada H, Riego-Ruiz L, González A Tags: Trends Genet Source Type: research

Genomic and Phenomic Research in the 21st Century.
Abstract The field of human genomics has changed dramatically over time. Initial genomic studies were predominantly restricted to rare disorders in small families. Over the past decade, researchers changed course from family-based studies and instead focused on common diseases and traits in populations of unrelated individuals. With further advancements in biobanking, computer science, electronic health record (EHR) data, and more affordable high-throughput genomics, we are experiencing a new paradigm in human genomic research. Rapidly changing technologies and resources now make it possible to study thousands of ...
Source: Trends in Genetics : TIG - October 17, 2018 Category: Genetics & Stem Cells Authors: Hebbring S Tags: Trends Genet Source Type: research

Post-transcriptional Regulatory Functions of Mammalian Pumilio Proteins.
Abstract Mammalian Pumilio proteins, PUM1 and PUM2, are members of the PUF family of sequence-specific RNA-binding proteins. In this review, we explore their mechanisms, regulatory networks, biological functions, and relevance to diseases. Pumilio proteins bind an extensive network of mRNAs and repress protein expression by inhibiting translation and promoting mRNA decay. Opposingly, in certain contexts, they can activate protein expression. Pumilio proteins also regulate noncoding (nc)RNAs. The ncRNA, ncRNA activated by DNA damage (NORAD), can in turn modulate Pumilio activity. Genetic analysis provides new insig...
Source: Trends in Genetics : TIG - October 10, 2018 Category: Genetics & Stem Cells Authors: Goldstrohm AC, Hall TMT, McKenney KM Tags: Trends Genet Source Type: research

Rhythms of the Genome: Circadian Dynamics from Chromatin Topology, Tissue-Specific Gene Expression, to Behavior.
Abstract Circadian rhythms in physiology and behavior evolved to resonate with daily cycles in the external environment. In mammals, organs orchestrate temporal physiology over the 24-h day, which requires extensive gene expression rhythms targeted to the right tissue. Although a core set of gene products oscillates across virtually all cell types, gene expression profiling across tissues over the 24-h day showed that rhythmic gene expression programs are tissue specific. We highlight recent progress in uncovering how the circadian clock interweaves with tissue-specific gene regulatory networks involving functions...
Source: Trends in Genetics : TIG - October 8, 2018 Category: Genetics & Stem Cells Authors: Yeung J, Naef F Tags: Trends Genet Source Type: research

The Birth of the 3D Genome during Early Embryonic Development.
Abstract The 3D structure of chromatin in the nucleus is important for the regulation of gene expression and the correct deployment of developmental programs. The differentiation of germ cells and early embryonic development (when the zygotic genome is activated and transcription is taking place for the first time) are accompanied by dramatic changes in gene expression and the epigenetic landscape. Recent studies used Hi-C to investigate the 3D chromatin organization during these developmental transitions, uncovering remarkable remodeling of the 3D genome. Here, we highlight the changes described so far and discus...
Source: Trends in Genetics : TIG - October 3, 2018 Category: Genetics & Stem Cells Authors: Hug CB, Vaquerizas JM Tags: Trends Genet Source Type: research

Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies.
Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies. Trends Genet. 2018 Oct 01;: Authors: Wienert B, Martyn GE, Funnell APW, Quinlan KGR, Crossley M Abstract Disorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to be characterized and remain among the most common and best understood genetic conditions. Moreover, the study of the β-globin locus provides a textbook example of developmental gene regulation. The fetal γ-globin genes (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is replaced by the adult β-glob...
Source: Trends in Genetics : TIG - October 1, 2018 Category: Genetics & Stem Cells Authors: Wienert B, Martyn GE, Funnell APW, Quinlan KGR, Crossley M Tags: Trends Genet Source Type: research

Improving Estimates of Compensatory cis-trans Regulatory Divergence.
Abstract Interspecific hybrids have played a key role in research on gene expression regulation. A growing number of studies have measured genome-wide allele-specific expression in hybrids and observed that cis-regulatory changes often oppose trans-acting changes affecting the same genes, suggesting stabilizing selection for compensatory changes. However, the most common method for estimating these effects is biased, producing artifactual patterns of compensatory evolution. Here I introduce a simple modification leveraging biological replicates that ameliorates the bias. PMID: 30270122 [PubMed - as supplied b...
Source: Trends in Genetics : TIG - September 27, 2018 Category: Genetics & Stem Cells Authors: Fraser HB Tags: Trends Genet Source Type: research

Easy Access to and Applications of the Sequences of All Protein-Coding Genes of All Sequenced Mouse Strains.
Abstract An easily accessible and searchable overview of all protein sequences in the 36 genome-sequenced mouse strains, compared to those in the reference strain C57BL/6J, is now available, as well as an overview of the aberrant proteins in this reference strain. We provide an insight into the advantages of using these databases. PMID: 30243593 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 19, 2018 Category: Genetics & Stem Cells Authors: Timmermans S, Libert C Tags: Trends Genet Source Type: research

The Generic Facet of Hox Protein Function.
Abstract Hox transcription factors are essential to promote morphological diversification of the animal body. A substantial number of studies have focused on how Hox proteins reach functional specificity, an issue that arises from the fact that these transcription factors control distinct developmental functions despite sharing similar molecular properties. In this review, we highlight that, besides specific functions, for which these transcription factors are renowned, Hox proteins also often have nonspecific functions. We next discuss some emerging principles of these generic functions and how they relate to spe...
Source: Trends in Genetics : TIG - September 18, 2018 Category: Genetics & Stem Cells Authors: Saurin AJ, Delfini MC, Maurel-Zaffran C, Graba Y Tags: Trends Genet Source Type: research

Drilling for Insight: Forecasting Phenotype from Genotype.
Abstract The manifestation of disease can vary substantially from person to person. Yet, much of the emphasis of genomics in individualized medicine has been on linking genetic variants to broad disease categories. A new approach takes a first step towards predicting detailed phenotypic information from disease-causative variants. PMID: 30220472 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 13, 2018 Category: Genetics & Stem Cells Authors: Torkamani A Tags: Trends Genet Source Type: research

Parallels between Mammalian Mechanisms of Monoallelic Gene Expression.
Abstract Different types of monoallelic gene expression are present in mammals, some of which are highly flexible, whereas others are more rigid. These include allelic exclusion at antigen receptor loci, the expression of olfactory receptor genes, genomic imprinting, X-chromosome inactivation, and random monoallelic expression (MAE). Although these processes play diverse biological roles, and arose through different selective pressures, the underlying epigenetic mechanisms show striking resemblances. Regulatory transcriptional events are important in all systems, particularly in the specification of MAE. Combined ...
Source: Trends in Genetics : TIG - September 11, 2018 Category: Genetics & Stem Cells Authors: Khamlichi AA, Feil R Tags: Trends Genet Source Type: research

Pimp My Ribosome: Ribosomal Protein Paralogs Specify Translational Control.
Abstract The ability of cells to grow and divide, differentiate and function, and even senesce is dependent on the fine-tuning of both gene and protein expression. Protein concentration in the cell is regulated not only at the transcriptional and post-translational levels, but also at the level of translation. Ribosomes, the molecular machines behind translation, were once considered to be an invariant driving force behind protein expression. However, studies over the past decade paint a rather different picture; namely, that ribosomes constitute an additional layer of regulatory control that might define which su...
Source: Trends in Genetics : TIG - September 5, 2018 Category: Genetics & Stem Cells Authors: Gerst JE Tags: Trends Genet Source Type: research

Transposons, p53 and Genome Security.
Abstract p53, the most commonly mutated tumor suppressor, is a transcription factor known to regulate proliferation, senescence, and apoptosis. Compelling studies have found that p53 may prevent oncogenesis through effectors that are unrelated to these canonical processes and recent findings have uncovered ancient roles for p53 in the containment of mobile elements. Together, these developments raise the possibility that some p53-driven cancers could result from unrestrained transposons. Here, we explore evidence linking conserved features of p53 biology to the control of transposons. We also show how p53-deficien...
Source: Trends in Genetics : TIG - September 5, 2018 Category: Genetics & Stem Cells Authors: Tiwari B, Jones AE, Abrams JM Tags: Trends Genet Source Type: research

RNA, Action through Interactions.
Abstract As transcription of the human genome is quite pervasive, it is possible that many novel functions of the noncoding genome have yet to be identified. Often the noncoding genome's functions are carried out by their RNA transcripts, which may rely on their structures and/or extensive interactions with other molecules. Recent technology developments are transforming the fields of RNA biology from studying one RNA at a time to transcriptome-wide mapping of structures and interactions. Here, we highlight the recent advances in transcriptome-wide RNA interaction analysis. These technologies revealed surprising v...
Source: Trends in Genetics : TIG - August 31, 2018 Category: Genetics & Stem Cells Authors: Nguyen TC, Zaleta-Rivera K, Huang X, Dai X, Zhong S Tags: Trends Genet Source Type: research

The Neural Mechanisms of Sexually Dimorphic Aggressive Behaviors.
Abstract Aggression is a fundamental social behavior that is essential for competing for resources and protecting oneself and families in both males and females. As a result of natural selection, aggression is often displayed differentially between the sexes, typically at a higher level in males than females. Here, we highlight the behavioral differences between male and female aggression in rodents. We further outline the aggression circuits in males and females, and compare their differences at each circuit node. Lastly, we summarize our current understanding regarding the generation of sexually dimorphic aggres...
Source: Trends in Genetics : TIG - August 30, 2018 Category: Genetics & Stem Cells Authors: Hashikawa K, Hashikawa Y, Lischinsky J, Lin D Tags: Trends Genet Source Type: research

Analysis of Epistasis in Natural Traits Using Model Organisms.
Abstract The ability to detect and understand epistasis in natural populations is important for understanding how biological traits are influenced by genetic variation. However, identification and characterization of epistasis in natural populations remains difficult due to statistical issues that arise as a result of multiple comparisons, and the fact that most genetic variants segregate at low allele frequencies. In this review, we discuss how model organisms may be used to manipulate genotypic combinations to power the detection of epistasis as well as test interactions between specific genes. Findings from a n...
Source: Trends in Genetics : TIG - August 27, 2018 Category: Genetics & Stem Cells Authors: Campbell RF, McGrath PT, Paaby AB Tags: Trends Genet Source Type: research

Co-expression in Single-Cell Analysis: Saving Grace or Original Sin?
Abstract As a fundamental unit of life, the cell has rightfully been the subject of intense investigation throughout the history of biology. Technical innovations now make it possible to assay cellular features at genomic scale, yielding breakthroughs in our understanding of the molecular organization of tissues, and even whole organisms. As these data accumulate we will soon be faced with a new challenge: making sense of the plethora of results. Early investigations into the replicability of cell type profiles inferred from single-cell RNA sequencing data have indicated that this is likely to be surprisingly stra...
Source: Trends in Genetics : TIG - August 23, 2018 Category: Genetics & Stem Cells Authors: Crow M, Gillis J Tags: Trends Genet Source Type: research

Epigenetic Environmental Memories in Plants: Establishment, Maintenance, and Reprogramming.
Abstract Plants are immobile and must respond to or endure fluctuating surroundings and diverse environmental challenges. Environmental inputs often induce chromatin modifications at various responsive genes and consequent changes in their expression. Environment-induced chromatin marks at certain loci are transmittable through cell divisions after relief from the original external signals, leading to acquired 'memorization' of environmental experiences in plants, namely epigenetic environmental memories, which enable plants to adapt to environmental changes or to perform better when events recur. Here, we review ...
Source: Trends in Genetics : TIG - August 22, 2018 Category: Genetics & Stem Cells Authors: He Y, Li Z Tags: Trends Genet Source Type: research

Enter the Matrix: Factorization Uncovers Knowledge from Omics.
Abstract Omics data contain signals from the molecular, physical, and kinetic inter- and intracellular interactions that control biological systems. Matrix factorization (MF) techniques can reveal low-dimensional structure from high-dimensional data that reflect these interactions. These techniques can uncover new biological knowledge from diverse high-throughput omics data in applications ranging from pathway discovery to timecourse analysis. We review exemplary applications of MF for systems-level analyses. We discuss appropriate applications of these methods, their limitations, and focus on the analysis of resu...
Source: Trends in Genetics : TIG - August 21, 2018 Category: Genetics & Stem Cells Authors: Stein-O'Brien GL, Arora R, Culhane AC, Favorov AV, Garmire LX, Greene CS, Goff LA, Li Y, Ngom A, Ochs MF, Xu Y, Fertig EJ Tags: Trends Genet Source Type: research

Complex-Trait Prediction in the Era of Big Data.
Abstract Accurate prediction of complex traits requires using a large number of DNA variants. Advances in statistical and machine learning methodology enable the identification of complex patterns in high-dimensional settings. However, training these highly parameterized methods requires very large data sets. Until recently, such data sets were not available. But the situation is changing rapidly as very large biomedical data sets comprising individual genotype-phenotype data for hundreds of thousands of individuals become available in public and private domains. We argue that the convergence of advances in method...
Source: Trends in Genetics : TIG - August 20, 2018 Category: Genetics & Stem Cells Authors: de Los Campos G, Vazquez AI, Hsu S, Lello L Tags: Trends Genet Source Type: research

Giving the Genes a Shuffle: Using Natural Variation to Understand Host Genetic Contributions to Viral Infections.
Abstract The laboratory mouse has proved an invaluable model to identify host factors that regulate the progression and outcome of virus-induced disease. The paradigm is to use single-gene knockouts in inbred mouse strains or genetic mapping studies using biparental mouse populations. However, genetic variation among these mouse strains is limited compared with the diversity seen in human populations. To address this disconnect, a multiparental mouse population has been developed to specifically dissect the multigenetic regulation of complex disease traits. The Collaborative Cross (CC) population of recombinant in...
Source: Trends in Genetics : TIG - August 18, 2018 Category: Genetics & Stem Cells Authors: Leist SR, Baric RS Tags: Trends Genet Source Type: research

Beyond Promoters: How Genes Tweak Their Own Expression.
acute;zsi G Abstract The 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. PMID: 30119990 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - August 14, 2018 Category: Genetics & Stem Cells Authors: Székely T, Balázsi G Tags: Trends Genet Source Type: research

Spermatogenesis and the Evolution of Mammalian Sex Chromosomes.
Abstract Developmental 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 evolution, and how these attributes may contribute to speciation. We argue that a developmental context is fundamental t...
Source: Trends in Genetics : TIG - August 1, 2018 Category: Genetics & Stem Cells Authors: Larson EL, Kopania EEK, Good JM Tags: Trends Genet Source Type: research

Nimble and Ready to Mingle: Transposon Outbursts of Early Development.
Abstract Transposable 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. However, it remains an open question how such an evolutionarily divergent set can mediate such conserved developmental p...
Source: Trends in Genetics : TIG - July 26, 2018 Category: Genetics & Stem Cells Authors: Rodriguez-Terrones D, Torres-Padilla ME Tags: Trends Genet Source Type: research

Experimental Studies of Evolutionary Dynamics in Microbes.
Abstract Evolutionary 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 have made it possible to observe evolutionary dynamics at unprecedented resolution. These new methods can now begin to ...
Source: Trends in Genetics : TIG - July 16, 2018 Category: Genetics & Stem Cells Authors: Cvijović I, Nguyen Ba AN, Desai MM Tags: Trends Genet Source Type: research

New and Prospective Roles for lncRNAs in Organelle Formation and Function.
Abstract The 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 soluble RNA-protein sub-organelles. This review explores the possibilities enabled by t...
Source: Trends in Genetics : TIG - July 14, 2018 Category: Genetics & Stem Cells Authors: Krause HM Tags: Trends Genet Source Type: research

Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls.
Abstract The 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 of these transcripts becomes a daunting task. The solution to this complex challenge likely lies in deep unders...
Source: Trends in Genetics : TIG - July 12, 2018 Category: Genetics & Stem Cells Authors: Cao H, Wahlestedt C, Kapranov P Tags: Trends Genet Source Type: research

Single-Cell Multi-omics: An Engine for New Quantitative Models of Gene Regulation.
Abstract Cells 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 yet powerful approach to relate gene expression to other aspects of cellular state, and in doin...
Source: Trends in Genetics : TIG - July 11, 2018 Category: Genetics & Stem Cells Authors: Packer J, Trapnell C Tags: Trends Genet Source Type: research

Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective.
Abstract The 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 TF2BM), one transcription elongation (TEFM), and one known transcription termination factor (mTERF1). Recent findings ...
Source: Trends in Genetics : TIG - June 23, 2018 Category: Genetics & Stem Cells Authors: Barshad G, Marom S, Cohen T, Mishmar D Tags: Trends Genet Source Type: research

The Third Revolution in Sequencing Technology.
Abstract Forty 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 unprecedented quality. Moreover, these technologies can directly detect epigenetic modifications on native DNA and allow whole-transcript sequenc...
Source: Trends in Genetics : TIG - June 22, 2018 Category: Genetics & Stem Cells Authors: van Dijk EL, Jaszczyszyn Y, Naquin D, Thermes C Tags: Trends Genet Source Type: research

P-Bodies: Cytosolic Droplets for Coordinated mRNA Storage.
Abstract P-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 insights into their function. Together with recent innovative imaging studies, these new data show...
Source: Trends in Genetics : TIG - June 13, 2018 Category: Genetics & Stem Cells Authors: Standart N, Weil D Tags: Trends Genet Source Type: research

Gene Editing on Center Stage.
Abstract Smithies 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 widespread use of genome editing was enabled by the discovery of the clustered regularly interspaced short palindromic repeats (CR...
Source: Trends in Genetics : TIG - June 13, 2018 Category: Genetics & Stem Cells Authors: Bak RO, Gomez-Ospina N, Porteus MH Tags: Trends Genet Source Type: research

Genetic Network Complexity Shapes Background-Dependent Phenotypic Expression.
Abstract The 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 given mutation may shape its propensity of exhibiting background-dependent phenotypes. We argue that further efforts in systematica...
Source: Trends in Genetics : TIG - June 11, 2018 Category: Genetics & Stem Cells Authors: Hou J, van Leeuwen J, Andrews BJ, Boone C Tags: Trends Genet Source Type: research

Harnessing Tumor Evolution to Circumvent Resistance.
Abstract High-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 emergence of resistance, as well as approaches that seek to forestall resistance by targeting tumor evolution. ...
Source: Trends in Genetics : TIG - June 11, 2018 Category: Genetics & Stem Cells Authors: Pogrebniak KL, Curtis CN Tags: Trends Genet Source Type: research

Transcribing Centromeres: Noncoding RNAs and Kinetochore Assembly.
Abstract Chromosome 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 localization. At least some centromeres have promoter activity, and many have non-B form DNA that ...
Source: Trends in Genetics : TIG - June 2, 2018 Category: Genetics & Stem Cells Authors: Talbert PB, Henikoff S Tags: Trends Genet Source Type: research

Comparing Apples to Apples and Oranges to Oranges.
Abstract A 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. PMID: 29853203 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - May 28, 2018 Category: Genetics & Stem Cells Authors: Bourque G Tags: Trends Genet Source Type: research

DNA Modifications: Naturally More Error Prone?
r B Abstract Epigenetic 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 DNA modifications and other mutagenic processes. External mutagens, such as UV light or smoking carcinogens, ...
Source: Trends in Genetics : TIG - May 28, 2018 Category: Genetics & Stem Cells Authors: Tomkova M, Schuster-Böckler B Tags: Trends Genet Source Type: research

Rad5, HLTF, and SHPRH: A Fresh View of an Old Story.
Abstract Not 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. PMID: 29807746 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - May 25, 2018 Category: Genetics & Stem Cells Authors: Elserafy M, Abugable AA, Atteya R, El-Khamisy SF Tags: Trends Genet Source Type: research

Long-Distance Relationships: Suppression of Repeat-Mediated Deletions.
Abstract The 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. PMID: 29804746 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - May 24, 2018 Category: Genetics & Stem Cells Authors: Morales ME, Kaul T, Deininger P Tags: Trends Genet Source Type: research

Genetic-Driven Druggable Target Identification and Validation.
Abstract Choosing 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 criteria for the optimal use of genetic findings in the drug discovery pipeline. PMID: 29803319 [PubMed - as supplied by publisher...
Source: Trends in Genetics : TIG - May 23, 2018 Category: Genetics & Stem Cells Authors: Floris M, Olla S, Schlessinger D, Cucca F Tags: Trends Genet Source Type: research

Break-Induced Replication: The Where, The Why, and The How.
Abstract Break-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 missing. Recent studies have uncovered multiple examples of BIR working in replication restart and...
Source: Trends in Genetics : TIG - May 4, 2018 Category: Genetics & Stem Cells Authors: Kramara J, Osia B, Malkova A Tags: Trends Genet 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. PMID: 29731376 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - May 3, 2018 Category: Genetics & Stem Cells Authors: Dou Y, Gold HD, Luquette LJ, Park PJ Tags: Trends Genet Source Type: research

Why Do Sex Chromosomes Stop Recombining?
Abstract It 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 drive, heterozygote advantage, and genetic drift, respectively. We contrast the hypotheses, the situations when they are likely to...
Source: Trends in Genetics : TIG - April 28, 2018 Category: Genetics & Stem Cells Authors: Ponnikas S, Sigeman H, Abbott JK, Hansson B Tags: Trends Genet Source Type: research

Replicability and Prediction: Lessons and Challenges from GWAS.
rro A Abstract Since 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 plagued by false positives. At a time of increasing concerns about the lack of reproducibility, we examine the biological and methodologica...
Source: Trends in Genetics : TIG - April 28, 2018 Category: Genetics & Stem Cells Authors: Marigorta UM, Rodríguez JA, Gibson G, Navarro A Tags: Trends Genet Source Type: research

The Evolution of Gene Expression in cis and trans.
Abstract There 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 (through diffusible products of other genes) and their contribution to adaptation and response to the envir...
Source: Trends in Genetics : TIG - April 18, 2018 Category: Genetics & Stem Cells Authors: Signor SA, Nuzhdin SV Tags: Trends Genet Source Type: research

Forensic Epigenetic Age Estimation and Beyond: Ethical and Legal Considerations.
Abstract Forensic 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. PMID: 29674182 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - April 16, 2018 Category: Genetics & Stem Cells Authors: Shabani M, Borry P, Smeers I, Bekaert B Tags: Trends Genet Source Type: research

Reflections of a Biomedical Scientist on Four Continents in Interdisciplinary Research.
PMID: 29636189 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - April 7, 2018 Category: Genetics & Stem Cells Authors: Reichardt JKV Tags: Trends Genet Source Type: research

Perspectives on Glycosylation and Its Congenital Disorders.
Abstract Congenital 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 comprehensive genetic tools specifically tailored for mammalian cell-based models have revealed a cr...
Source: Trends in Genetics : TIG - March 29, 2018 Category: Genetics & Stem Cells Authors: Ng BG, Freeze HH Tags: Trends Genet Source Type: research

SMC Complexes: Universal DNA Looping Machines with Distinct Regulators.
Abstract What 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 implications for how these complexes ultimately shape chromosomes. A picture is emerging in which these co...
Source: Trends in Genetics : TIG - March 29, 2018 Category: Genetics & Stem Cells Authors: van Ruiten MS, Rowland BD Tags: Trends Genet Source Type: research

ALS Genes in the Genomic Era and their Implications for FTD.
Abstract Amyotrophic 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 identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential releva...
Source: Trends in Genetics : TIG - March 28, 2018 Category: Genetics & Stem Cells Authors: Nguyen HP, Van Broeckhoven C, van der Zee J Tags: Trends Genet Source Type: research