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Trends in Genetics: TIG

Ali Torkamani
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.
September 13, 2018: Trends in Genetics: TIG
Ahmed Amine Khamlichi, Robert Feil
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...
September 11, 2018: Trends in Genetics: TIG
Bhavana Tiwari, Amanda E Jones, John M Abrams
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...
September 5, 2018: Trends in Genetics: TIG
Jeffrey E Gerst
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 subsets of mRNAs are translated, to what extent, and to what purpose...
September 5, 2018: Trends in Genetics: TIG
Tri C Nguyen, Kathia Zaleta-Rivera, Xuerui Huang, Xiaofeng Dai, Sheng Zhong
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...
August 31, 2018: Trends in Genetics: TIG
Koichi Hashikawa, Yoshiko Hashikawa, Julieta Lischinsky, Dayu Lin
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 aggression circuits during development and their maintenance during adulthood...
August 30, 2018: Trends in Genetics: TIG
Richard F Campbell, Patrick T McGrath, Annalise B Paaby
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...
August 27, 2018: Trends in Genetics: TIG
Megan Crow, Jesse Gillis
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 straightforward due to consistent gene co-expression...
August 23, 2018: Trends in Genetics: TIG
Yuehui He, Zicong Li
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...
August 22, 2018: Trends in Genetics: TIG
Genevieve L Stein-O'Brien, Raman Arora, Aedin C Culhane, Alexander V Favorov, Lana X Garmire, Casey S Greene, Loyal A Goff, Yifeng Li, Aloune Ngom, Michael F Ochs, Yanxun Xu, Elana J Fertig
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 results to facilitate optimal biological interpretation...
August 21, 2018: Trends in Genetics: TIG
Gustavo de Los Campos, Ana Ines Vazquez, Stephen Hsu, Louis Lello
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...
August 20, 2018: Trends in Genetics: TIG
Sarah R Leist, Ralph S Baric
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...
August 18, 2018: Trends in Genetics: TIG
Tamás Székely, Gábor Balázsi
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.
August 14, 2018: Trends in Genetics: TIG
Diego Rodriguez-Terrones, Maria-Elena Torres-Padilla
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 processes...
July 26, 2018: Trends in Genetics: TIG
Henry M Krause
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...
July 14, 2018: Trends in Genetics: TIG
Erica L Larson, Emily E K Kopania, Jeffrey M Good
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...
September 2018: Trends in Genetics: TIG
Ivana Cvijović, Alex N Nguyen Ba, Michael M Desai
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...
September 2018: Trends in Genetics: TIG
Huifen Cao, Claes Wahlestedt, Philipp Kapranov
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...
September 2018: Trends in Genetics: TIG
Jonathan Packer, Cole Trapnell
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 doing so, gain insights into the biochemical mechanisms that are necessary to produce a given gene expression output...
September 2018: Trends in Genetics: TIG
Gilad Barshad, Shani Marom, Tal Cohen, Dan Mishmar
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)...
September 2018: Trends in Genetics: TIG
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