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Trends in Genetics: TIG

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https://www.readbyqxmd.com/read/28292534/synonymous-codons-choose-wisely-for-expression
#1
REVIEW
Christina E Brule, Elizabeth J Grayhack
The genetic code, which defines the amino acid sequence of a protein, also contains information that influences the rate and efficiency of translation. Neither the mechanisms nor functions of codon-mediated regulation were well understood. The prevailing model was that the slow translation of codons decoded by rare tRNAs reduces efficiency. Recent genome-wide analyses have clarified several issues. Specific codons and codon combinations modulate ribosome speed and facilitate protein folding. However, tRNA availability is not the sole determinant of rate; rather, interactions between adjacent codons and wobble base pairing are key...
March 11, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28268034/epistasis-in-neuropsychiatric-disorders
#2
REVIEW
Caleb Webber
The contribution of epistasis to human disease remains unclear. However, several studies have now identified epistatic interactions between common variants that increase the risk of a neuropsychiatric disorder, while there is growing evidence that genetic interactions contribute to the pathogenicity of rare, multigenic copy-number variants (CNVs) that have been observed in patients. This review discusses the current evidence for epistatic events and genetic interactions in neuropsychiatric disorders, how paradigm shifts in the phenotypic classification of patients would empower the search for epistatic effects, and how network and cellular models might be employed to further elucidate relevant epistatic interactions...
March 3, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28245910/genomics-of-islet-dys-function-and-type-2-diabetes
#3
REVIEW
Nathan Lawlor, Shubham Khetan, Duygu Ucar, Michael L Stitzel
Pancreatic islet dysfunction and beta cell failure are hallmarks of type 2 diabetes mellitus (T2DM) pathogenesis. In this review, we discuss how genome-wide association studies (GWASs) and recent developments in islet (epi)genome and transcriptome profiling (particularly single cell analyses) are providing novel insights into the genetic, environmental, and cellular contributions to islet (dys)function and T2DM pathogenesis. Moving forward, study designs that interrogate and model genetic variation [e.g., allelic profiling and (epi)genome editing] will be critical to dissect the molecular genetics of T2DM pathogenesis, to build next-generation cellular and animal models, and to develop precision medicine approaches to detect, treat, and prevent islet (dys)function and T2DM...
February 25, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28236503/y-and-w-chromosome-assemblies-approaches-and-discoveries
#4
REVIEW
Marta Tomaszkiewicz, Paul Medvedev, Kateryna D Makova
Hundreds of vertebrate genomes have been sequenced and assembled to date. However, most sequencing projects have ignored the sex chromosomes unique to the heterogametic sex - Y and W - that are known as sex-limited chromosomes (SLCs). Indeed, haploid and repetitive Y chromosomes in species with male heterogamety (XY), and W chromosomes in species with female heterogamety (ZW), are difficult to sequence and assemble. Nevertheless, obtaining their sequences is important for understanding the intricacies of vertebrate genome function and evolution...
February 21, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28222895/the-epigenetic-regulator-smchd1-in-development-and-disease
#5
REVIEW
Natasha Jansz, Kelan Chen, James M Murphy, Marnie E Blewitt
It has very recently become clear that the epigenetic modifier SMCHD1 has a role in two distinct disorders: facioscapulohumoral muscular dystrophy (FSHD) and Bosma arhinia and micropthalmia (BAMS). In the former there are heterozygous loss-of-function mutations, while both gain- and loss-of-function mutations have been proposed to underlie the latter. These findings have led to much interest in SMCHD1 and how it works at the molecular level. We summarise here current understanding of the mechanism of action of SMCHD1, its role in these diseases, and what has been learnt from study of mouse models null for Smchd1 in the decade since the discovery of SMCHD1...
February 17, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28196760/polycomb-group-systems-in-fungi-new-models-for-understanding-polycomb-repressive-complex-2
#6
REVIEW
Zachary A Lewis
Polycomb group (PcG) proteins form multiple complexes that direct assembly of transcriptionally repressed chromatin, an essential process for multicellular development. Recent studies in plants and animals have uncovered surprising complexity in the form of multiple, variant PcG complexes governed by an extensive regulatory network. PcG proteins are absent from major yeast models, but recent research revealed minimal PcG systems in several well-studied fungi. In both animals and fungi, PcG complexes are responsive to local chromatin structure, but important aspects of PcG regulation remain unknown...
February 11, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28174022/the-evolution-and-genetics-of-carotenoid-processing-in-animals
#7
REVIEW
David P L Toews, Natalie R Hofmeister, Scott A Taylor
Coloration is one of the most conspicuous traits that varies among organisms. Carotenoid pigments are responsible for many of the red, orange, and yellow colors in the natural world and, at least for most animals, these molecules must be acquired from their environment. Identifying genes important for carotenoid transport, deposition, and processing has been difficult, in contrast to the well-characterized genes involved in the melanogenesis pathways. We review recent progress in the genetics of carotenoid processing, advances owing in part to the application of high-throughput sequencing data...
February 4, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28174021/biogenesis-and-function-of-ago-associated-rnas
#8
REVIEW
Iben Daugaard, Thomas Birkballe Hansen
Numerous sophisticated high-throughput sequencing technologies have been developed over the past decade, and these have enabled the discovery of a diverse catalog of small non-coding (nc)RNA molecules that function as regulatory entities by associating with Argonaute (Ago) proteins. MicroRNAs (miRNAs) are currently the best-described class of post-transcriptional regulators that follow a specific biogenesis pathway characterized by Drosha/DGCR8 and Dicer processing. However, more exotic miRNA-like species that bypass particular steps of the canonical miRNA biogenesis pathway continue to emerge, with one of the most recent additions being the agotrons, which escape both Drosha/DGCR8- and Dicer-processing...
February 4, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28174020/necessity-is-the-mother-of-invention-ciliates-transposons-and-transgenerational-inheritance
#9
REVIEW
Sarah E Allen, Mariusz Nowacki
Ciliates are a fascinating model system for the study of the interaction between eukaryotic germlines and somatic lines, especially with regard to the invasion and defence against transposable elements. They separate their germline and somatic line into two nuclei within the same cell, and they silence transposons and repetitive elements by way of deleting them from their somatic genome. This large-scale deletion event uses a series of intricate sequence targeting pathways involving small RNAs and transposases, part of which consists of a transnuclear comparison between maternal soma and daughter germline...
February 4, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28174019/understanding-idiopathic-scoliosis-a-new-zebrafish-school-of-thought
#10
REVIEW
Curtis W Boswell, Brian Ciruna
Idiopathic scoliosis (IS) refers to a 3D rotation of the spine that occurs in the absence of underlying vertebral anomalies or obvious physiological defects. Despite affecting approximately 4% of the population, the etiology and pathogenesis of IS remain poorly understood, largely due to genetic heterogeneity and historical lack of appropriate developmental models. Recently, zebrafish has emerged as a powerful system for studying IS, owing to well-developed genetic resources and a natural susceptibility to spinal curvatures...
February 4, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28174018/evolving-plastic-responses-to-external-and-genetic-environments
#11
Max Reuter, M Florencia Camus, Mark S Hill, Filip Ruzicka, Kevin Fowler
Phenotypic plasticity can mitigate adaptive trade-offs in fluctuating environments but how plasticity arises is little known. New research documents this process in a bacterial system. We highlight remarkable parallels to the evolution of sexual dimorphism and argue that their approach can aid our understanding of adaptive conflicts between the sexes.
February 4, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28069312/centromeres-drive-a-hard-bargain
#12
REVIEW
Leah F Rosin, Barbara G Mellone
Centromeres are essential chromosomal structures that mediate the accurate distribution of genetic material during meiotic and mitotic cell divisions. In most organisms, centromeres are epigenetically specified and propagated by nucleosomes containing the centromere-specific H3 variant, centromere protein A (CENP-A). Although centromeres perform a critical and conserved function, CENP-A and the underlying centromeric DNA are rapidly evolving. This paradox has been explained by the centromere drive hypothesis, which proposes that CENP-A is undergoing an evolutionary tug-of-war with selfish centromeric DNA...
January 7, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28104289/nuclear-dynamics-of-heterochromatin-repair
#13
REVIEW
Nuno Amaral, Taehyun Ryu, Xiao Li, Irene Chiolo
Repairing double-strand breaks (DSBs) is particularly challenging in pericentromeric heterochromatin, where the abundance of repeated sequences exacerbates the risk of ectopic recombination and chromosome rearrangements. Recent studies in Drosophila cells revealed that faithful homologous recombination (HR) repair of heterochromatic DSBs relies on the relocalization of DSBs to the nuclear periphery before Rad51 recruitment. We summarize here the exciting progress in understanding this pathway, including conserved responses in mammalian cells and surprising similarities with mechanisms in yeast that deal with DSBs in distinct sites that are difficult to repair, including other repeated sequences...
February 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28089370/single-cell-multiomics-multiple-measurements-from-single-cells
#14
REVIEW
Iain C Macaulay, Chris P Ponting, Thierry Voet
Single-cell sequencing provides information that is not confounded by genotypic or phenotypic heterogeneity of bulk samples. Sequencing of one molecular type (RNA, methylated DNA or open chromatin) in a single cell, furthermore, provides insights into the cell's phenotype and links to its genotype. Nevertheless, only by taking measurements of these phenotypes and genotypes from the same single cells can such inferences be made unambiguously. In this review, we survey the first experimental approaches that assay, in parallel, multiple molecular types from the same single cell, before considering the challenges and opportunities afforded by these and future technologies...
February 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28087167/lingering-questions-about-enhancer-rna-and-enhancer-transcription-coupled-genomic-instability
#15
REVIEW
Gerson Rothschild, Uttiya Basu
Intergenic and intragenic enhancers found inside topologically associated regulatory domains (TADs) express noncoding RNAs, known as enhancer RNAs (eRNAs). Recent studies have indicated these eRNAs play a role in gene regulatory networks by controlling promoter and enhancer interactions and topology of higher-order chromatin structure. Misregulation of enhancer and promoter associated noncoding RNAs (ncRNAs) could stabilize deleterious secondary DNA structures, noncoding RNA associated DNA/RNA hybrid formation, and promote collisions of transcription complexes with replisomes...
February 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28012572/mammalian-polycistronic-mrnas-and-disease
#16
REVIEW
Timofey A Karginov, Daniel Parviz Hejazi Pastor, Bert L Semler, Christopher M Gomez
Our understanding of gene expression has come far since the 'one-gene one-polypeptide' hypothesis proposed by Beadle and Tatum. In this review, we address the gradual recognition that a growing number of polycistronic genes, originally discovered in viruses, are being identified within the mammalian genome, and that these may provide new insights into disease mechanisms and treatment. We carried out a systematic literature review identifying 13 mammalian genes for which there is evidence for polycistronic expression via translation through an internal ribosome entry site (IRES)...
February 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27939749/mining-the-unknown-assigning-function-to-noncoding-single-nucleotide-polymorphisms
#17
REVIEW
Sierra S Nishizaki, Alan P Boyle
One of the formative goals of genetics research is to understand how genetic variation leads to phenotypic differences and human disease. Genome-wide association studies (GWASs) bring us closer to this goal by linking variation with disease faster than ever before. Despite this, GWASs alone are unable to pinpoint disease-causing single nucleotide polymorphisms (SNPs). Noncoding SNPs, which represent the majority of GWAS SNPs, present a particular challenge. To address this challenge, an array of computational tools designed to prioritize and predict the function of noncoding GWAS SNPs have been developed...
January 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27939252/a-matter-of-time-small-rnas-regulate-the-duration-of-epigenetic-inheritance
#18
REVIEW
Leah Houri-Zeevi, Oded Rechavi
Small RNAs are increasingly emerging as transgenerational carriers of epigenetic information in Caenorhabditis elegans and in other organisms. Recent studies have identified factors that are required for the inheritance of small RNAs and for heritable RNAi in worms, which typically persist for a finite number of generations. We examine here recent insights into the mechanisms that control the duration of transgenerational inheritance of small RNAs. We discuss current understanding of two types of regulatory mechanisms: those that prolong RNAi inheritance through amplification and maintenance of heritable small RNAs, and those that limit the persistence of ancestral RNAi by, for example, employing negative feedback loops to reset the transmission of epigenetic information...
January 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27931778/a-magic-spot-in-genome-maintenance
#19
REVIEW
Aviram Rasouly, Bibhusita Pani, Evgeny Nudler
Nucleotide excision repair (NER) is the key DNA repair system that eliminates the majority of DNA helix-distorting lesions. RNA polymerase (RNAP) expedites the recognition of DNA damage by NER components via transcription-coupled DNA repair (TCR). In bacteria, a modified nucleotide ppGpp ('magic spot') is a pleiotropic second messenger that mediates the response to nutrient deficiencies by altering the initiation properties of RNAP. In this review, we discuss newly elucidated roles of guanosine 5'-diphosphate 3'-diphosphate (ppGpp) in transcription elongation that couple this alarmone to DNA damage repair and maintenance...
January 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27916428/highly-signal-responsive-gene-regulatory-network-governing-myxococcus-development
#20
REVIEW
Lee Kroos
The bacterium Myxococcus xanthus undergoes multicellular development when starved. Thousands of cells build mounds in which some differentiate into spores. This remarkable feat and the genetic tractability of Myxococcus provide a unique opportunity to understand the evolution of gene regulatory networks (GRNs). Recent work has revealed a GRN involving interconnected cascades of signal-responsive transcriptional activators. Initially, starvation-induced intracellular signals direct changes in gene expression...
January 2017: Trends in Genetics: TIG
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