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

What Do You Think Makes a Good Undergraduate Laboratory Research Project?
Authors: PMID: 29573817 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - March 21, 2018 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research

Understanding Alzheimer Disease at the Interface between Genetics and Transcriptomics.
Abstract Over 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, reveal allele-specific events connecting AD risk genes to expression profiles, and provide conve...
Source: Trends in Genetics : TIG - March 21, 2018 Category: Genetics & Stem Cells Authors: Verheijen J, Sleegers K Tags: Trends Genet Source Type: research

Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.
Abstract Over 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 patients. There is a notable disconnect between these two bodies of knowledge: knockouts poorly appr...
Source: Trends in Genetics : TIG - March 19, 2018 Category: Genetics & Stem Cells Authors: McGinty RJ, Mirkin SM Tags: Trends Genet Source Type: research

Do you incorporate recent literature or themes from your own research into your genetics courses?
Authors: PMID: 29540286 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - March 11, 2018 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research

How Do You Design Undergraduate Genetics Laboratory Courses?
Authors: PMID: 29525438 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - March 7, 2018 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research

Genetic Villains: Killer Meiotic Drivers.
Zanders SE Abstract Unbiased 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 products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses o...
Source: Trends in Genetics : TIG - February 27, 2018 Category: Genetics & Stem Cells Authors: Bravo Núñez MA, Nuckolls NL, Zanders SE Tags: Trends Genet Source Type: research

Sphingolipid Turnover Turns Over the Fate of Aneuploid Cells.
te; Z Abstract Aneuploidy, or unbalanced chromosome number, is a hallmark of cancer. Recently established model systems revealed that aneuploidy affects many aspects of cellular physiology, among them sphingolipid metabolism. The new finding that the proliferation of aneuploid cells depends on sphingolipid homeostasis offers an appealing opportunity for cancer treatment. PMID: 29477508 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - February 21, 2018 Category: Genetics & Stem Cells Authors: Storchová Z Tags: Trends Genet Source Type: research

What aspect(s) of genetics do you think most excites students in your classes?
Authors: PMID: 29433761 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - February 9, 2018 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research

What Genetic Concept(s) Do You Think Are the Hardest for the Students to Grasp?
Authors: PMID: 29433762 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - February 9, 2018 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research

Switch and Trace: Recombinase Genetics in Zebrafish.
Abstract Transgenic approaches are instrumental for labeling and manipulating cells and cellular machineries in vivo. Transgenes have traditionally been static entities that remained unaltered following genome integration, limiting their versatility. The development of DNA recombinase-based methods to modify, excise, or rearrange transgene cassettes has introduced versatile control of transgene activity and function. In particular, recombinase-controlled transgenes enable regulation of exogenous gene expression, conditional mutagenesis, and genetic lineage tracing. In zebrafish, transgenesis-based recombinase gene...
Source: Trends in Genetics : TIG - February 8, 2018 Category: Genetics & Stem Cells Authors: Carney TJ, Mosimann C Tags: Trends Genet Source Type: research

Through Sex, Nature Is Telling Us Something Important.
Abstract Theoretically, a variety of mechanisms can make amphimixis advantageous due to reshuffling of offspring genotypes. Recently, it has been shown experimentally that some of these mechanisms can indeed work in artificial populations. However, we still do not know which of them, if any, are relevant in nature, and the available indirect estimates seem to suggest that neither negative nor positive selection in natural populations is strong enough to provide evolutionary protection for obligate amphimixis. Thus, progress in understanding the evolution of amphimixis will depend on direct measurements of the stre...
Source: Trends in Genetics : TIG - February 3, 2018 Category: Genetics & Stem Cells Authors: Kondrashov AS Tags: Trends Genet Source Type: research

Deregulation of CRTCs in Aging and Age-Related Disease Risk: (Trends in Genetics, 33, 303-321, 2017).
ir WB PMID: 29398010 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - February 1, 2018 Category: Genetics & Stem Cells Authors: Escoubas CC, Silva-García CG, Mair WB Tags: Trends Genet Source Type: research

Stable Intronic Sequence RNAs Engage in Feedback Loops.
Abstract Stable intronic sequence RNAs (sisRNAs) are conserved in various organisms. Recent observations in Drosophila suggest that sisRNAs often engage in regulatory feedback loops to control the expression of their parental genes. The use of sisRNAs as mediators for local feedback control may be a general phenomenon. PMID: 29397203 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 31, 2018 Category: Genetics & Stem Cells Authors: Pek JW Tags: Trends Genet Source Type: research

RNA Biology in Retinal Development and Disease.
Abstract For decades, RNA has served in a supporting role between the genetic carrier (DNA) and the functional molecules (proteins). It is finally time for RNA to take center stage in all aspects of biology. The retina provides a unique opportunity to dissect the molecular underpinnings of neuronal diversity and disease. Transcriptome profiles of the retina and its resident cell types have unraveled unique features of the RNA landscape. The discovery of distinct RNA molecules and the recognition that RNA processing is a major cause of retinal neurodegeneration have prompted the design of biomarkers and novel thera...
Source: Trends in Genetics : TIG - January 30, 2018 Category: Genetics & Stem Cells Authors: Zelinger L, Swaroop A Tags: Trends Genet Source Type: research

A Toolkit of Engineered Recombinational Balancers in C. elegans.
Abstract Dejima and colleagues report using CRISPR/Cas9 to generate a new collection of greatly improved balancer chromosomes in the standard laboratory nematode Caenorhabditis elegans, using methods previously reported by the same laboratory, expanding the set of C. elegans balancers to cover nearly 90% of coding genes. PMID: 29395380 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 30, 2018 Category: Genetics & Stem Cells Authors: Schwartz HT, Sternberg PW Tags: Trends Genet Source Type: research

Time for Bed: Genetic Mechanisms Mediating the Circadian Regulation of Sleep.
Abstract Sleep is an evolutionarily conserved behavior that is increasingly recognized as important for human health. While its precise function remains controversial, sleep has been suggested to play a key role in a variety of biological phenomena ranging from synaptic plasticity to metabolic clearance. Although it is clear that sleep is regulated by the circadian clock, how this occurs remains enigmatic. Here we examine the genetic mechanisms by which the circadian clock regulates sleep, drawing on recent work in fruit flies, zebrafish, mice, and humans. These studies reveal that central and local clocks utilize...
Source: Trends in Genetics : TIG - January 24, 2018 Category: Genetics & Stem Cells Authors: Blum ID, Bell B, Wu MN Tags: Trends Genet Source Type: research

The Definition of Open Reading Frame Revisited.
Abstract The term open reading frame (ORF) is of central importance to gene finding. Surprisingly, at least three definitions are in use. We discuss several molecular biological and bioinformatics aspects, and we recommend using the definition in which an ORF is bounded by stop codons. PMID: 29366605 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 20, 2018 Category: Genetics & Stem Cells Authors: Sieber P, Platzer M, Schuster S Tags: Trends Genet Source Type: research

PRDM9 and Its Role in Genetic Recombination.
Abstract PRDM9 is a zinc finger protein that binds DNA at specific locations in the genome where it trimethylates histone H3 at lysines 4 and 36 at surrounding nucleosomes. During meiosis in many species, including humans and mice where PRDM9 has been most intensely studied, these actions determine the location of recombination hotspots, where genetic recombination occurs. In addition, PRDM9 facilitates the association of hotspots with the chromosome axis, the site of the programmed DNA double-strand breaks (DSBs) that give rise to genetic exchange between chromosomes. In the absence of PRDM9 DSBs are not properly...
Source: Trends in Genetics : TIG - January 20, 2018 Category: Genetics & Stem Cells Authors: Paigen K, Petkov PM Tags: Trends Genet Source Type: research

Caught with One's Zinc Fingers in the Genome Integrity Cookie Jar.
Abstract Zinc finger (ZnF) domains are present in at least 5% of human proteins. First characterized as binding to DNA, ZnFs display extraordinary binding plasticity and can bind to RNA, lipids, proteins, and protein post-translational modifications (PTMs). The diverse binding properties of ZnFs have made their functional characterization challenging. While once confined to large and poorly characterized protein families, proteomic, cellular, and molecular studies have begun to shed light on their involvement as protectors of the genome. We focus here on the emergent roles of ZnF domain-containing proteins in prom...
Source: Trends in Genetics : TIG - January 19, 2018 Category: Genetics & Stem Cells Authors: Vilas CK, Emery LE, Denchi EL, Miller KM Tags: Trends Genet Source Type: research

Big Strides in Cellular MicroRNA Expression.
Abstract A lack of knowledge of the cellular origin of miRNAs has greatly confounded functional and biomarkers studies. Recently, three studies characterized miRNA expression patterns across>78 human cell types. These combined data expand our knowledge of miRNA expression localization and confirm that many miRNAs show cell type-specific expression patterns. PMID: 29361313 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 17, 2018 Category: Genetics & Stem Cells Authors: Halushka MK, Fromm B, Peterson KJ, McCall MN Tags: Trends Genet Source Type: research

mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease.
Abstract Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of th...
Source: Trends in Genetics : TIG - January 15, 2018 Category: Genetics & Stem Cells Authors: Kapur M, Ackerman SL Tags: Trends Genet Source Type: research

Computational Strategies for Exploring Circular RNAs.
Abstract Recent studies have demonstrated that circular RNAs (circRNAs) are ubiquitous and have diverse functions and mechanisms of biogenesis. In these studies, computational profiling of circRNAs has been prevalently used as an indispensable method to provide high-throughput approaches to detect and analyze circRNAs. However, without an overall understanding of the underlying strategies, these computational methods may not be appropriately selected or used for a specific research purpose, and some misconceptions may result in biases in the analyses. In this review we attempt to illustrate the key steps and summa...
Source: Trends in Genetics : TIG - January 12, 2018 Category: Genetics & Stem Cells Authors: Gao Y, Zhao F Tags: Trends Genet Source Type: research

Detecting and Avoiding Problems When Using the Cre-lox System.
Abstract The Cre-lox recombination approach is commonly used to generate cell-specific gene inactivation (or activation). We have noticed that the breeding and genotyping sections of papers utilizing Cre-lox techniques are frequently incomplete. While seemingly straightforward, there are important considerations that need to be implemented in the breeding and genotyping methods to prevent the introduction of experimental confounds. Germline recombination and transient expression of Cre recombinase during development are some examples of the complications that can occur, and conventional genotyping methods may fail...
Source: Trends in Genetics : TIG - January 11, 2018 Category: Genetics & Stem Cells Authors: Song AJ, Palmiter RD Tags: Trends Genet Source Type: research

Defining B Cell Chromatin: Lessons from EBF1.
Abstract Hematopoiesis is regulated by signals from the microenvironment, transcription factor networks, and changes of the epigenetic landscape. Transcription factors interact with and shape chromatin to allow for lineage- and cell type-specific changes in gene expression. During B lymphopoiesis, epigenetic regulation is observed in multilineage progenitors in which a specific chromatin context is established, at the onset of the B cell differentiation when early B cell factor 1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J recombination and after antigen-driven activation of B cells and term...
Source: Trends in Genetics : TIG - January 11, 2018 Category: Genetics & Stem Cells Authors: Boller S, Li R, Grosschedl R Tags: Trends Genet Source Type: research

Supervised Machine Learning for Population Genetics: A New Paradigm.
Abstract As population genomic datasets grow in size, researchers are faced with the daunting task of making sense of a flood of information. To keep pace with this explosion of data, computational methodologies for population genetic inference are rapidly being developed to best utilize genomic sequence data. In this review we discuss a new paradigm that has emerged in computational population genomics: that of supervised machine learning (ML). We review the fundamentals of ML, discuss recent applications of supervised ML to population genetics that outperform competing methods, and describe promising future dire...
Source: Trends in Genetics : TIG - January 10, 2018 Category: Genetics & Stem Cells Authors: Schrider DR, Kern AD Tags: Trends Genet Source Type: research

Regulatory Potential of the RNA Processing Machinery: Implications for Human Disease.
Abstract Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels. These findings have impo...
Source: Trends in Genetics : TIG - January 9, 2018 Category: Genetics & Stem Cells Authors: Carey KT, Wickramasinghe VO Tags: Trends Genet Source Type: research

Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells.
Abstract While the vast majority of cellular DNA in eukaryotes is contained in long linear strands in chromosomes, we have long recognized some exceptions like mitochondrial DNA, plasmids in yeasts, and double minutes (DMs) in cancer cells where the DNA is present in extrachromosomal circles. In addition, specialized extrachromosomal circles of DNA (eccDNA) have been noted to arise from repetitive genomic sequences like telomeric DNA or rDNA. Recently eccDNA arising from unique (nonrepetitive) DNA have been discovered in normal and malignant cells, raising interesting questions about their biogenesis, function and...
Source: Trends in Genetics : TIG - January 9, 2018 Category: Genetics & Stem Cells Authors: Paulsen T, Kumar P, Koseoglu MM, Dutta A Tags: Trends Genet Source Type: research

What Are Some of the Major Challenges in Teaching/Designing Genetics Courses Today?
Authors: PMID: 29291902 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - December 29, 2017 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research

How Do You Incorporate 21st Century Genetics into Your Undergraduate Course?
Authors: PMID: 29291903 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - December 29, 2017 Category: Genetics & Stem Cells Tags: Trends Genet Source Type: research