Alternative mRNA transcription, processing, and translation: insights from RNA sequencing.
Abstract The human transcriptome comprises>80000 protein-coding transcripts and the estimated number of proteins synthesized from these transcripts is in the range of 250000 to 1 million. These transcripts and proteins are encoded by less than 20000 genes, suggesting extensive regulation at the transcriptional, post-transcriptional, and translational level. Here we review how RNA sequencing (RNA-seq) technologies have increased our understanding of the mechanisms that give rise to alternative transcripts and their alternative translation. We highlight four different regulatory processes: alternative transcripti...
Source: Trends in Genetics : TIG - January 30, 2015 Category: Genetics & Stem Cells Authors: de Klerk E, 't Hoen PA Tags: Trends Genet Source Type: research

Nuclear rRNA transcript processing versus internal transcribed spacer secondary structure.
Abstract rRNA is one of the few universal features of life, making it uniquely suited to assess phylogenetic relationships. The processing of the initial polycistronic rRNA transcript is also a conserved process, involving numerous cleavage events and the generation of secondary structures. The secondary structure of the internal transcribed spacer (ITS) regions of nuclear rRNA transcripts are well known for a wide variety of eukaryotes and have been used to aid in the alignment of these sequences for phylogenetic comparisons. By contrast, study of the processing of the initial rRNA transcripts has been largely li...
Source: Trends in Genetics : TIG - January 30, 2015 Category: Genetics & Stem Cells Authors: Coleman AW Tags: Trends Genet Source Type: research

From trans to cis: transcriptional regulatory networks in neocortical development.
Abstract Transcriptional mechanisms mediated by the binding of transcription factors (TFs) to cis-acting regulatory elements (CREs) in DNA play crucial roles in directing gene expression. While TFs have been extensively studied, less effort has gone towards the identification and functional characterization of CREs and associated epigenetic modulation. However, owing to methodological and analytical advances, more comprehensive studies of regulatory elements and mechanisms are now possible. We summarize recent progress in integrative analyses of these regulatory components in the development of the cerebral neocor...
Source: Trends in Genetics : TIG - January 23, 2015 Category: Genetics & Stem Cells Authors: Shibata M, Gulden FO, Sestan N Tags: Trends Genet Source Type: research

Paths to a malaria vaccine illuminated by parasite genomics.
Abstract More human death and disease is caused by malaria parasites than by all other eukaryotic pathogens combined. As early as the sequencing of the first human genome, malaria parasite genomics was prioritized to fuel the discovery of vaccine candidate antigens. This stimulated increased research on malaria, generating new understanding of the cellular and molecular mechanisms of infection and immunity. This review of recent developments illustrates how new approaches in parasite genomics, and increasingly large amounts of data from population studies, are helping to identify antigens that are promising lead t...
Source: Trends in Genetics : TIG - January 22, 2015 Category: Genetics & Stem Cells Authors: Conway DJ Tags: Trends Genet Source Type: research

NIH's genomic data sharing policy: timing and tradeoffs.
Abstract NIH's new genomic data sharing (GDS) policy covers both human and model-organism genotypic and phenotypic data, and strives to balance rapid release of data with embargo periods to ensure that data producers have sufficient time to analyze their results. But how well does the policy achieve this balance? PMID: 25620797 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 22, 2015 Category: Genetics & Stem Cells Authors: Contreras JL Tags: Trends Genet Source Type: research

The H3Africa policy framework: negotiating fairness in genomics.
Abstract Human Heredity and Health in Africa (H3Africa) research seeks to promote fair collaboration between scientists in Africa and those from elsewhere. Here, we outline how concerns over inequality and exploitation led to a policy framework that places a firm focus on African leadership and capacity building as guiding principles for African genomics research. PMID: 25601285 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 15, 2015 Category: Genetics & Stem Cells Authors: de Vries J, Tindana P, Littler K, Ramsay M, Rotimi C, Abayomi A, Mulder N, Mayosi BM Tags: Trends Genet Source Type: research

Accounting for uncertainty in DNA sequencing data.
Abstract Science is defined in part by an honest exposition of the uncertainties that arise in measurements and propagate through calculations and inferences, so that the reliabilities of its conclusions are made apparent. The recent rapid development of high-throughput DNA sequencing technologies has dramatically increased the number of measurements made at the biochemical and molecular level. These data come from many different DNA-sequencing technologies, each with their own platform-specific errors and biases, which vary widely. Several statistical studies have tried to measure error rates for basic determinat...
Source: Trends in Genetics : TIG - January 8, 2015 Category: Genetics & Stem Cells Authors: O'Rawe JA, Ferson S, Lyon GJ Tags: Trends Genet Source Type: research

Why we need more ecology for genetic models such as C. elegans.
Abstract Functional information about the large majority of the genes is still lacking in the classical eukaryotic model species Drosophila melanogaster, Caenorhabditis elegans, and Mus musculus. Because many of these genes are likely to be important in natural settings, considering explicit ecological information should increase our knowledge of gene function. Using C. elegans as an example, we discuss the importance of biotic factors as a driving force in shaping the composition and structure of the nematode genome. We highlight examples for which consideration of ecological information and natural variation hav...
Source: Trends in Genetics : TIG - January 7, 2015 Category: Genetics & Stem Cells Authors: Petersen C, Dirksen P, Schulenburg H Tags: Trends Genet Source Type: research

An epigenetic escape route.
Abstract Some of our fate is predetermined, by genetics and by the environment in the womb. Gestational environments are reflected in the DNA methylomes of newborns, in a manner that is often influenced by genotype. Therefore, DNA methylation serves as molecular mechanism linking the interplay of early life environments and genetics to later life health. As such, methylation marks are potential biomarkers of suboptimal developmental trajectories. Can DNA methylation also be used to construct an escape route from biological fate? PMID: 25547197 [PubMed - in process] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - January 1, 2015 Category: Genetics & Stem Cells Authors: Holbrook JD Tags: Trends Genet Source Type: research

Is pigment patterning in fish skin determined by the Turing mechanism?
Abstract More than half a century ago, Alan Turing postulated that pigment patterns may arise from a mechanism that could be mathematically modeled based on the diffusion of two substances that interact with each other. Over the past 15 years, the molecular and genetic tools to verify this prediction have become available. Here, we review experimental studies aimed at identifying the mechanism underlying pigment pattern formation in zebrafish. Extensive molecular genetic studies in this model organism have revealed the interactions between the pigment cells that are responsible for the patterns. The mechanism disc...
Source: Trends in Genetics : TIG - December 24, 2014 Category: Genetics & Stem Cells Authors: Watanabe M, Kondo S Tags: Trends Genet Source Type: research

Genetic research on biospecimens poses minimal risk.
Abstract Genetic research on human biospecimens is increasingly common. However, debate continues over the level of risk that this research poses to sample donors. Some argue that genetic research on biospecimens poses minimal risk; others argue that it poses greater than minimal risk and therefore needs additional requirements and limitations. This debate raises concern that some donors are not receiving appropriate protection or, conversely, that valuable research is being subject to unnecessary requirements and limitations. The present paper attempts to resolve this debate using the widely-endorsed 'risks of da...
Source: Trends in Genetics : TIG - December 16, 2014 Category: Genetics & Stem Cells Authors: Wendler DS, Rid A Tags: Trends Genet Source Type: research

Integrating phenotypic small-molecule profiling and human genetics: the next phase in drug discovery.
Abstract Over the past decade, tremendous progress in high-throughput small molecule-screening methods has facilitated the rapid expansion of phenotype-based data. Parallel advances in genomic characterization methods have complemented these efforts by providing a growing list of annotated cell line features. Together, these developments have paved the way for feature-based identification of novel, exploitable cellular dependencies, subsequently expanding our therapeutic toolkit in cancer and other diseases. Here, we provide an overview of the evolution of phenotypic small-molecule profiling and discuss the most s...
Source: Trends in Genetics : TIG - December 11, 2014 Category: Genetics & Stem Cells Authors: Johannessen CM, Clemons PA, Wagner BK Tags: Trends Genet Source Type: research

Human knockout research: new horizons and opportunities.
Abstract Although numerous approaches have been pursued to understand the function of human genes, Mendelian genetics has by far provided the most compelling and medically actionable dataset. Biallelic loss-of-function (LOF) mutations are observed in the majority of autosomal recessive Mendelian disorders, representing natural human knockouts and offering a unique opportunity to study the physiological and developmental context of these genes. The restriction of such context to 'disease' states is artificial, however, and the recent ability to survey entire human genomes for biallelic LOF mutations has revealed a ...
Source: Trends in Genetics : TIG - December 8, 2014 Category: Genetics & Stem Cells Authors: Alkuraya FS Tags: Trends Genet Source Type: research

On the meaning of the word 'epimutation': a comment.
PMID: 25480537 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - December 2, 2014 Category: Genetics & Stem Cells Authors: Yu DH, Waterland RA, Shen L Tags: Trends Genet Source Type: research

Thinking too positive? Revisiting current methods of population genetic selection inference.
Abstract In the age of next-generation sequencing, the availability of increasing amounts and improved quality of data at decreasing cost ought to allow for a better understanding of how natural selection is shaping the genome than ever before. However, alternative forces, such as demography and background selection (BGS), obscure the footprints of positive selection that we would like to identify. In this review, we illustrate recent developments in this area, and outline a roadmap for improved selection inference. We argue (i) that the development and obligatory use of advanced simulation tools is necessary for ...
Source: Trends in Genetics : TIG - December 1, 2014 Category: Genetics & Stem Cells Authors: Bank C, Ewing GB, Ferrer-Admettla A, Foll M, Jensen JD Tags: Trends Genet Source Type: research

Whitey crumbles.
Abstract Despite scientific evidence to the contrary, cultural notions that incorrectly aggrandize genetic differences between ethnicities persist. New work on the genetic makeup of Europeans now shows even more definitively how false those notions are. PMID: 25443044 [PubMed - in process] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - December 1, 2014 Category: Genetics & Stem Cells Authors: Klitz W Tags: Trends Genet Source Type: research

'Pitfalls in the application of gene set analysis to genetics studies': a response.
PMID: 25459302 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - November 19, 2014 Category: Genetics & Stem Cells Authors: Mooney MA, Nigg JT, McWeeney SK, Wilmot B Tags: Trends Genet Source Type: research

Pitfalls in the application of gene-set analysis to genetics studies.
Pavlidis P Abstract Gene-set analysis (GSA) ('enrichment') is a popular approach for the interpretation of genome-wide association studies (GWASs). GSA is most commonly applied to the analysis of transcriptomes, but from the outset it has been considered useful for any study that provides rankings or 'hit lists' of genes. The recent review by Mooney et al.[1] is a valuable resource for geneticists wishing to apply GSA to the output of GWASs. Here we describe some additional points of practical importance if the methods are to be applied and interpreted soundly. PMID: 25459301 [PubMed - as supplied by publish...
Source: Trends in Genetics : TIG - November 14, 2014 Category: Genetics & Stem Cells Authors: Sedeño-Cortés AE, Pavlidis P Tags: Trends Genet Source Type: research

Balancing the welfare: the use of non-human primates in research.
Abstract Until now, there have been no ideal alternatives to replace non-human primates (NHPs) in biomedical research, yet the debate on whether it is appropriate to sacrifice NHPs for research never stops. With recent advances in genomics and the appearance of new technologies, the time is right to return to the problem of finding solutions to balance the welfare of both humans and NHPs. PMID: 25438695 [PubMed - in process] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - November 1, 2014 Category: Genetics & Stem Cells Authors: Zhou Q Tags: Trends Genet Source Type: research

Unreduced gametes: meiotic mishap or evolutionary mechanism?
Abstract Unreduced gametes (gametes with the somatic chromosome number) are known to facilitate polyploid formation. Unreduced gametes result from a plethora of different mechanisms across different taxa, suggesting that the ability to produce unreduced gametes has evolutionary utility. Heritable genetic variation for unreduced gamete production has been observed, thereby providing an evolutionary substrate. Unreduced gametes are also frequently involved in interspecific hybridisation events as well as being produced by interspecific hybrids, facilitating allopolyploidisation. Environmental stress often triggers u...
Source: Trends in Genetics : TIG - October 16, 2014 Category: Genetics & Stem Cells Authors: Mason AS, Pires JC Tags: Trends Genet Source Type: research

Topological features of rugged fitness landscapes in sequence space.
Abstract The factors that determine the tempo and mode of protein evolution continue to be a central question in molecular evolution. Traditionally, studies of protein evolution focused on the rates of amino acid substitutions. More recently, with the availability of sequence data and advanced experimental techniques, the focus of attention has shifted toward the study of evolutionary trajectories and the overall layout of protein fitness landscapes. In this review we describe the effect of epistasis on the topology of evolutionary pathways that are likely to be found in fitness landscapes and develop a simple the...
Source: Trends in Genetics : TIG - October 15, 2014 Category: Genetics & Stem Cells Authors: Kondrashov DA, Kondrashov FA Tags: Trends Genet Source Type: research

On the shoulders of worms.
PMID: 25306101 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - October 8, 2014 Category: Genetics & Stem Cells Authors: Macrae R Tags: Trends Genet Source Type: research

Engineering allostery.
Abstract Allosteric proteins have great potential in synthetic biology, but our limited understanding of the molecular underpinnings of allostery has hindered the development of designer molecules, including transcription factors with new DNA-binding or ligand-binding specificities that respond appropriately to inducers. Such allosteric proteins could function as novel switches in complex circuits, metabolite sensors, or as orthogonal regulators for independent, inducible control of multiple genes. Advances in DNA synthesis and next-generation sequencing technologies have enabled the assessment of millions of muta...
Source: Trends in Genetics : TIG - October 8, 2014 Category: Genetics & Stem Cells Authors: Raman S, Taylor N, Genuth N, Fields S, Church GM Tags: Trends Genet Source Type: research

On the meaning of the word 'epimutation'
Abstract The word 'epimutation' is often used in a manner that can be misinterpreted. The strict definition of epimutation is a heritable change in gene activity that is not associated with a DNA mutation but rather with gain or loss of DNA methylation or other heritable modifications of chromatin. Unfortunately, there is a growing tendency in the cancer field to use the word in situations in which underlying DNA sequence changes have occurred. PMID: 25301328 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - October 6, 2014 Category: Genetics & Stem Cells Authors: Oey H, Whitelaw E Tags: Trends Genet Source Type: research

Higher-order genetic interactions and their contribution to complex traits.
Abstract The contribution of genetic interactions involving three or more loci to complex traits is poorly understood. These higher-order genetic interactions (HGIs) are difficult to detect in genetic mapping studies, therefore, few examples of them have been described. However, the lack of data on HGIs should not be misconstrued as proof that this class of genetic effect is unimportant. To the contrary, evidence from model organisms suggests that HGIs frequently influence genetic studies and contribute to many complex traits. Here, we review the growing literature on HGIs and discuss the future of research on thi...
Source: Trends in Genetics : TIG - October 2, 2014 Category: Genetics & Stem Cells Authors: Taylor MB, Ehrenreich IM Tags: Trends Genet Source Type: research

Sex differences in disease genetics: evidence, evolution, and detection.
Abstract Understanding the genetic architecture of disease is an enormous challenge, and should be guided by evolutionary principles. Recent studies in evolutionary genetics show that sexual selection can have a profound influence on the genetic architecture of complex traits. Here, we summarise data from heritability studies and genome-wide association studies (GWASs) showing that common genetic variation influences many diseases and medically relevant traits in a sex-dependent manner. In addition, we discuss how the discovery of sex-dependent effects in population samples is improved by joint interaction analysi...
Source: Trends in Genetics : TIG - September 27, 2014 Category: Genetics & Stem Cells Authors: Gilks WP, Abbott JK, Morrow EH Tags: Trends Genet Source Type: research

Serving epigenetics before its time.
Abstract Society prizes the rapid translation of basic biological science into ways to prevent human illness. However, the premature rush to take murine epigenetic findings in these directions makes impossible demands on prospective parents and triggers serious social and ethical questions. PMID: 25242336 [PubMed - in process] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - September 27, 2014 Category: Genetics & Stem Cells Authors: Juengst ET, Fishman JR, McGowan ML, Settersten RA Tags: Trends Genet Source Type: research

Volatile evolution of long noncoding RNA repertoires: mechanisms and biological implications.
Abstract Thousands of genes encoding long noncoding RNAs (lncRNAs) have been identified in all vertebrate genomes thus far examined. The list of lncRNAs partaking in arguably important biochemical, cellular, and developmental activities is steadily growing. However, it is increasingly clear that lncRNA repertoires are subject to weak functional constraint and rapid turnover during vertebrate evolution. We discuss here some of the factors that may explain this apparent paradox, including relaxed constraint on sequence to maintain lncRNA structure/function, extensive redundancy in the regulatory circuits in which ln...
Source: Trends in Genetics : TIG - September 10, 2014 Category: Genetics & Stem Cells Authors: Kapusta A, Feschotte C Tags: Trends Genet Source Type: research

The overdue promise of short tandem repeat variation for heritability.
Abstract Short tandem repeat (STR) variation has been proposed as a major explanatory factor in the heritability of complex traits in humans and model organisms. However, we still struggle to incorporate STR variation into genotype-phenotype maps. We review here the promise of STRs in contributing to complex trait heritability and highlight the challenges that STRs pose due to their repetitive nature. We argue that STR variants are more likely than single-nucleotide variants to have epistatic interactions, reiterate the need for targeted assays to genotype STRs accurately, and call for more appropriate statistical...
Source: Trends in Genetics : TIG - August 30, 2014 Category: Genetics & Stem Cells Authors: Press MO, Carlson KD, Queitsch C Tags: Trends Genet Source Type: research

Dissecting complex traits using the Drosophila Synthetic Population Resource.
We describe studies using one such panel, the Drosophila Synthetic Population Resource (DSPR), and the implications for our understanding of the genetic basis of complex traits. In particular, we note that many loci of large effect appear to be multiallelic. If multiallelism is a general rule, analytical approaches designed to identify multiallelic variants should be a priority for both genome-wide association studies (GWASs) and multi-parental panels. PMID: 25175100 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - August 27, 2014 Category: Genetics & Stem Cells Authors: Long AD, Macdonald SJ, King EG Tags: Trends Genet Source Type: research

Worms, bacteria, and micronutrients: an elegant model of our diet.
Abstract Micronutrients are required in small proportions in a diet to carry out key metabolic roles for biomass and energy production. Humans receive micronutrients either directly from their diet or from gut microbiota that metabolize other nutrients. The nematode Caenorhabditis elegans and its bacterial diet provide a relatively simple and genetically tractable model to study both direct and microbe-mediated effects of micronutrients. Recently, this model has been used to gain insight into the relationship between micronutrients, physiology, and metabolism. In particular, two B-type vitamins, vitamin B12 and fo...
Source: Trends in Genetics : TIG - August 26, 2014 Category: Genetics & Stem Cells Authors: Yilmaz LS, Walhout AJ Tags: Trends Genet Source Type: research

Alternative splicing regulation of telomerase: a new paradigm?
Abstract Alternative splicing affects approximately 95% of eukaryotic genes, greatly expanding the coding capacity of complex genomes. Although our understanding of alternative splicing has increased rapidly, current knowledge of splicing regulation has largely been derived from studies of highly expressed mRNAs. Telomerase is a key example of a protein that is alternatively spliced, but it is expressed at very low levels and although it is known that misregulation of telomerase splicing is a hallmark of nearly all cancers, the details of this process are unclear. Here we review work showing that hTERT expression ...
Source: Trends in Genetics : TIG - August 26, 2014 Category: Genetics & Stem Cells Authors: Wong MS, Wright WE, Shay JW Tags: Trends Genet Source Type: research

Toward a new history and geography of human genes informed by ancient DNA.
Abstract Genetic information contains a record of the history of our species, and technological advances have transformed our ability to access this record. Many studies have used genome-wide data from populations today to learn about the peopling of the globe and subsequent adaptation to local conditions. Implicit in this research is the assumption that the geographic locations of people today are informative about the geographic locations of their ancestors in the distant past. However, it is now clear that long-range migration, admixture, and population replacement subsequent to the initial out-of-Africa expans...
Source: Trends in Genetics : TIG - August 25, 2014 Category: Genetics & Stem Cells Authors: Pickrell JK, Reich D Tags: Trends Genet Source Type: research

Wisdom from the fly.
Abstract Arguably, almost all research in Drosophila can be considered basic research, yet many of the most essential and fundamental concepts of human genetics were first decoded in the fly. Although the fly genome, which is organized into only four chromosomes, is approximately one-twentieth the size of the human genome, it contains roughly the same number of genes, and up to 75% of human disease-related genes have Drosophila homologues [1]. The fly was prized for its simplicity and utility even before such compelling homology with humans was apparent. Since Thomas Hunt Morgan began his seminal experiments over ...
Source: Trends in Genetics : TIG - August 23, 2014 Category: Genetics & Stem Cells Authors: Rieder LE, Larschan EN Tags: Trends Genet Source Type: research

Functional and genomic context in pathway analysis of GWAS data.
Abstract Gene set analysis (GSA) is a promising tool for uncovering the polygenic effects associated with complex diseases. However, the available techniques reflect a wide variety of hypotheses about how genetic effects interact to contribute to disease susceptibility. The lack of consensus about the best way to perform GSA has led to confusion in the field and has made it difficult to compare results across methods. A clear understanding of the various choices made during GSA - such as how gene sets are defined, how single-nucleotide polymorphisms (SNPs) are assigned to genes, and how individual SNP-level effect...
Source: Trends in Genetics : TIG - August 22, 2014 Category: Genetics & Stem Cells Authors: Mooney MA, Nigg JT, McWeeney SK, Wilmot B Tags: Trends Genet Source Type: research

Connections between TET proteins and aberrant DNA modification in cancer.
We present an overview of loss-of-function mutations and abnormal expression and regulation of TET proteins in hematological malignancies and solid tumors, and discuss the potential prognostic value of assessing TET mutations and 5hmC levels in cancer patients. We also address the crosstalk between TET and two critical enzymes involved in cell metabolism: O-linked β-N-acetylglucosamine transferase (OGT) and isocitrate dehydrogenase (IDH). Lastly, we discuss the therapeutic potential of targeting TET proteins and aberrant DNA methylation in cancer. PMID: 25132561 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - August 14, 2014 Category: Genetics & Stem Cells Authors: Huang Y, Rao A Tags: Trends Genet Source Type: research

mRNA transport meets membrane traffic.
e M Abstract Active transport and local translation of mRNAs ensure the appropriate spatial organization of proteins within cells. Recent work has shown that this process is intricately connected to membrane trafficking. Here, we focus on new findings obtained in fungal model systems. Important highlights are that RNA-binding proteins recognize cargo mRNA synergistically and that mRNAs are co-transported with membranous compartments such as the endoplasmic reticulum (ER) and endosomes. We further discuss a novel concept of endosome-coupled translation that loads shuttling endosomes with septin cargo, a process imp...
Source: Trends in Genetics : TIG - August 7, 2014 Category: Genetics & Stem Cells Authors: Jansen RP, Niessing D, Baumann S, Feldbrügge M Tags: Trends Genet Source Type: research

Ten years of next-generation sequencing technology.
Abstract Ten years ago next-generation sequencing (NGS) technologies appeared on the market. During the past decade, tremendous progress has been made in terms of speed, read length, and throughput, along with a sharp reduction in per-base cost. Together, these advances democratized NGS and paved the way for the development of a large number of novel NGS applications in basic science as well as in translational research areas such as clinical diagnostics, agrigenomics, and forensic science. Here we provide an overview of the evolution of NGS and discuss the most significant improvements in sequencing technologies ...
Source: Trends in Genetics : TIG - August 6, 2014 Category: Genetics & Stem Cells Authors: van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C Tags: Trends Genet Source Type: research

Whole-genome sequencing to control antimicrobial resistance.
SJ Abstract Following recent improvements in sequencing technologies, whole-genome sequencing (WGS) is positioned to become an essential tool in the control of antibiotic resistance, a major threat in modern healthcare. WGS has already found numerous applications in this area, ranging from the development of novel antibiotics and diagnostic tests through to antibiotic stewardship of currently available drugs via surveillance and the elucidation of the factors that allow the emergence and persistence of resistance. Numerous proof-of-principle studies have also highlighted the value of WGS as a tool for day-to-day ...
Source: Trends in Genetics : TIG - August 2, 2014 Category: Genetics & Stem Cells Authors: Köser CU, Ellington MJ, Peacock SJ Tags: Trends Genet Source Type: research

Automatic multigenic family annotation: risks and solutions.
and C Abstract A major challenge facing bioinformatics today is the efficient annotation of the exponential flow of genomic data. This has led to an increasing dependence on automatic annotation procedures, despite the relatively high error rates of these programs, particularly for multigenic families. We discuss here the errors and biases introduced by automatic genome annotations, focusing on issues with structural annotations of gene families, and suggest ways to overcome these limitations. PMID: 25017189 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - July 10, 2014 Category: Genetics & Stem Cells Authors: Fawal N, Li Q, Mathé C, Dunand C Tags: Trends Genet Source Type: research

Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches.
Abstract Defects in DNA repair pathways enable cancer cells to accumulate genomic alterations that contribute to their aggressive phenotype. However, tumors rely on residual DNA repair capacities to survive the damage induced by genotoxic stress. This dichotomy might explain why only isolated DNA repair pathways are inactivated in cancer cells. Accordingly, synergism has been observed between DNA-damaging drugs and targeted inhibitors of DNA repair. DNA repair pathways are generally thought of as mutually exclusive mechanistic units handling different types of lesions in distinct cell cycle phases. Recent preclini...
Source: Trends in Genetics : TIG - July 10, 2014 Category: Genetics & Stem Cells Authors: Dietlein F, Thelen L, Reinhardt HC Tags: Trends Genet Source Type: research

The embryo as a laboratory: quantifying transcription in Drosophila.
Abstract Transcriptional regulation of gene expression is fundamental to most cellular processes, including determination of cellular fates. Quantitative studies of transcription in cultured cells have led to significant advances in identifying mechanisms underlying transcriptional control. Recent progress allowed implementation of these same quantitative methods in multicellular organisms to ask how transcriptional regulation unfolds both in vivo and at the single molecule level in the context of embryonic development. Here we review some of these advances in early Drosophila development, which bring the embryo o...
Source: Trends in Genetics : TIG - July 5, 2014 Category: Genetics & Stem Cells Authors: Gregor T, Garcia HG, Little SC Tags: Trends Genet Source Type: research

Transcriptional regulatory functions of nuclear long noncoding RNAs.
Abstract Several nuclear localised intergenic long noncoding RNAs (lncRNAs) have been ascribed regulatory roles in transcriptional control and their number is growing rapidly. Initially, these transcripts were shown to function locally, near their sites of synthesis, by regulating the expression of neighbouring genes. More recently, lncRNAs have been demonstrated to interact with chromatin at several thousand different locations across multiple chromosomes and to modulate large-scale gene expression programs. Although the molecular mechanisms involved in targeting lncRNAs to distal binding sites remain poorly unde...
Source: Trends in Genetics : TIG - June 25, 2014 Category: Genetics & Stem Cells Authors: Vance KW, Ponting CP Tags: Trends Genet Source Type: research

Exposing synonymous mutations.
Abstract Synonymous codon changes, which do not alter protein sequence, were previously thought to have no functional consequence. Although this concept has been overturned in recent years, there is no unique mechanism by which these changes exert biological effects. A large repertoire of both experimental and bioinformatic methods has been developed to understand the effects of synonymous variants. Results from this body of work have provided global insights into how biological systems exploit the degeneracy of the genetic code to control gene expression, protein folding efficiency, and the coordinated expression...
Source: Trends in Genetics : TIG - June 19, 2014 Category: Genetics & Stem Cells Authors: Hunt RC, Simhadri VL, Iandoli M, Sauna ZE, Kimchi-Sarfaty C Tags: Trends Genet Source Type: research

Genome typing of nonhuman primate models: implications for biomedical research.
Abstract The success of personalized medicine rests on understanding the genetic variation between individuals. Thus, as medical practice evolves and variation among individuals becomes a fundamental aspect of clinical medicine, a thorough consideration of the genetic and genomic information concerning the animals used as models in biomedical research also becomes critical. In particular, nonhuman primates (NHPs) offer great promise as models for many aspects of human health and disease. These are outbred species exhibiting substantial levels of genetic variation; however, understanding of the contribution of this...
Source: Trends in Genetics : TIG - June 18, 2014 Category: Genetics & Stem Cells Authors: Haus T, Ferguson B, Rogers J, Doxiadis G, Certa U, Rose NJ, Teepe R, Weinbauer GF, Roos C Tags: Trends Genet Source Type: research

The emerging era of genomic data integration for analyzing splice isoform function.
We describe here emerging computational approaches that integrate such large-scale whole-transcriptome sequencing (RNA-seq) data for predicting the functions of alternatively spliced isoforms, and we discuss their applications in developmental and cancer biology. We outline future directions for isoform function prediction, emphasizing the need for heterogeneous genomic data integration and tissue-specific, dynamic isoform-level network modeling, which will allow the field to realize its full potential. PMID: 24951248 [PubMed - as supplied by publisher] (Source: Trends in Genetics : TIG)
Source: Trends in Genetics : TIG - June 17, 2014 Category: Genetics & Stem Cells Authors: Li HD, Menon R, Omenn GS, Guan Y Tags: Trends Genet Source Type: research

Eri1: a conserved enzyme at the crossroads of multiple RNA-processing pathways.
Abstract Eri1 is an evolutionarily conserved 3'-5' exoribonuclease that participates in 5.8S rRNA 3' end processing and turnover of replication-dependent histone mRNAs. Over the course of evolution, Eri1 has also been recruited into a variety of conserved and species-specific regulatory small RNA pathways that include endogenous small interfering (si)RNAs and miRNAs. Recent advances in Eri1 biology illustrate the importance of RNA metabolism in epigenetic gene regulation and illuminate common principles and players in RNA biogenesis and turnover. In this review, we highlight Eri1 as a member of a growing class of ...
Source: Trends in Genetics : TIG - June 11, 2014 Category: Genetics & Stem Cells Authors: Thomas MF, L'Etoile ND, Ansel KM Tags: Trends Genet Source Type: research

GC content evolution in coding regions of angiosperm genomes: a unifying hypothesis.
Ressayre A Abstract In angiosperms (as in other species), GC content varies along and between genes, within a genome, and between genomes of different species, but the reason for this distribution is still an open question. Grass genomes are particularly intriguing because they exhibit a strong bimodal distribution of genic GC content and a sharp 5'-3' decreasing GC content gradient along most genes. Here, we propose a unifying model to explain the main patterns of GC content variation at the gene and genome scale. We argue that GC content patterns could be mainly determined by the interactions between gene struc...
Source: Trends in Genetics : TIG - June 7, 2014 Category: Genetics & Stem Cells Authors: Glémin S, Clément Y, David J, Ressayre A Tags: Trends Genet Source Type: research

Sirtuins: guardians of mammalian healthspan.
Abstract The first link between sirtuins and longevity was made 15 years ago in yeast. These initial studies sparked efforts by many laboratories working in diverse model organisms to elucidate the relations between sirtuins, lifespan, and age-associated dysfunction. Here, we discuss the current understanding of how sirtuins relate to aging. We focus primarily on mammalian sirtuins SIRT1, SIRT3, and SIRT6, the three sirtuins for which the most relevant data are available. Strikingly, a large body of evidence now indicates that these and other mammalian sirtuins suppress a variety of age-related pathologies and pro...
Source: Trends in Genetics : TIG - May 27, 2014 Category: Genetics & Stem Cells Authors: Giblin W, Skinner ME, Lombard DB Tags: Trends Genet Source Type: research

Spatial organization of transcription in bacterial cells.
Abstract Prokaryotic transcription has been extensively studied over the past half a century. However, there often exists a gap between the structural, mechanistic description of transcription obtained from in vitro biochemical studies, and the cellular, phenomenological observations from in vivo genetic studies. It is now accepted that a living bacterial cell is a complex entity; the heterogeneous cellular environment is drastically different from the homogenous, well-mixed situation in vitro. Where molecules are inside a cell may be important for their function; hence, the spatial organization of different molec...
Source: Trends in Genetics : TIG - May 23, 2014 Category: Genetics & Stem Cells Authors: Weng X, Xiao J Tags: Trends Genet Source Type: research