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Current Issue of Trends in Genetics


Issue: Trends in Genetics
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Trends in Genetics

Jul 01, 2021

Volume 37Issue 7p603-684, e1-e2
Adolescent idiopathic scoliosis (AIS) is a debilitating spine disorder with onset typically during teenage years. AIS is characterized by abnormal 3D curvatures of the spine that causes a considerable degree of disability to affected individuals. As the name connotes (“idiopathic” meaning without a known cause), the biological mechanisms driving AIS have remained rather mysterious. Studies with the zebrafish have elucidated a pathway that involves cilia-driven flow of catecholamine-laden cerebrospinal fluid (CSF) and Urotensin II signaling from CSF-contacting neurons of the spinal cord to trunk musculature for proper spine development. On pages 612–615 of this issue, Sudipto Roy summarizes recent genetic data from AIS patients that point to a conservation of the zebrafish findings in the etiology of AIS. The cover illustrates an artist’s impression of scoliotic zebrafish. Cover credit: Color pencil-on-paper art work by Sudipto Roy....
Adolescent idiopathic scoliosis (AIS) is a debilitating spine disorder with onset typically during teenage years. AIS is characterized by abnormal 3D curvatures of the spine that causes a considerable degree of disability to affected individuals. As the name connotes (“idiopathic” meaning without a known cause), the biological mechanisms driving AIS have remained rather mysterious. Studies with the zebrafish have elucidated a pathway that involves cilia-driven flow of catecholamine-laden cerebrospinal fluid (CSF) and Urotensin II signaling from CSF-contacting neurons of the spinal cord to trunk musculature for proper spine development. On pages 612–615 of this issue, Sudipto Roy summarizes recent genetic data from AIS patients that point to a conservation of the zebrafish findings in the etiology of AIS. The cover illustrates an artist’s impression of scoliotic zebrafish. Cover credit: Color pencil-on-paper art work by Sudipto Roy.

Science & Society

  • Genetics in Drug Discovery

    • Alexis Hubaud,
    • Ajeet Pratap Singh
    Drug discovery is a complex process with high attrition rate: only about half of the compounds in advanced preclinical stages actually enter human trials. Key to these failures is our lack of understanding of human biology and the difficulties in translating our preclinical knowledge into cures. Here, we examine how genetics can be leveraged in drug discovery to understand and alter human biology.

Spotlight

  • Transposons Increase Transcriptional Complexity: The Good Parasite?

    • Joachim M. Surm,
    • Yehu Moran
    A recent study by Cosby et al. sheds light on the role of transposons in the adaptive evolution of their hosts. These genetic elements were thought to be largely deleterious. However, when coupled with alternative splicing, there appears to be an exponential increase in the diversity of proteins encoded, which display novel functions and are conserved by natural selection.

Forum

  • Nuclear Periphery and Telomere Maintenance: TERRA Joins the Stage

    • Katarína Juríková,
    • Peter De Wulf,
    • Emilio Cusanelli
    Long noncoding (lnc)RNAs derived from telomeres, the ends of linear eukaryotic chromosomes, help to maintain telomere length and stability by multiple means, including regulation of telomerase activity and recombination-based telomere maintenance. New findings in yeast promote a model in which telomere attachment to the nuclear envelope regulates telomere transcription and maintenance.
  • Adolescent Idiopathic Scoliosis: Fishy Tales of Crooked Spines

    • Sudipto Roy
    Adolescent idiopathic scoliosis (AIS) is a common skeletal disorder, characterized by abnormal spine curvatures. In zebrafish, cilia-driven cerebrospinal fluid flow and urotensin II pathway activity are required for proper spine morphogenesis. Genetic studies with AIS patients now establish a conservation of the zebrafish findings in the etiology of the disease.

Opinions

  • Protein Bait Hypothesis: circRNA-Encoded Proteins Competitively Inhibit Cognate Functional Isoforms

    • Huanqiang Zhao,
    • Qiongjie Zhou,
    • Xiaotian Li
    Open Access
    Recent studies have demonstrated that a large group of proteins encoded by circular RNAs (circRNAs) are likely to play a role in cancer development; however, there remains a substantial gap in our understanding of this group of proteins and their functional mechanisms involved. Therefore, we propose the protein bait hypothesis, which specifies that circRNA-encoded proteins compete with their cognate linearly spliced protein isoforms for binding molecules, preventing proper isoform functioning. This hypothesis may expand our understanding of the functional mechanisms of circRNA-encoded proteins and prove useful in elucidating the mechanisms underlying human development, physiology, and diseases, and in parallel, also aid in drug discovery.
  • Towards a Human Cell Atlas: Taking Notes from the Past

    • Rik G.H. Lindeboom,
    • Aviv Regev,
    • Sarah A. Teichmann
    Open Access
    Comprehensively characterizing the cellular composition and organization of tissues has been a long-term scientific challenge that has limited our ability to study fundamental and clinical aspects of human physiology. The Human Cell Atlas (HCA) is a global collaborative effort to create a reference map of all human cells as a basis for both understanding human health and diagnosing, monitoring, and treating disease. Many aspects of the HCA are analogous to the Human Genome Project (HGP), whose completion presents a major milestone in modern biology.
  • Polygenic Adaptation: Integrating Population Genetics and Gene Regulatory Networks

    • Maud Fagny,
    • Frédéric Austerlitz
    Open Access
    The adaptation of populations to local environments often relies on the selection of optimal values for polygenic traits. Here, we first summarize the results obtained from different quantitative genetics and population genetics models, about the genetic architecture of polygenic traits and their response to directional selection. We then highlight the contribution of systems biology to the understanding of the molecular bases of polygenic traits and the evolution of gene regulatory networks involved in these traits.

Feature Review

    Featured Article
  • DNA Repair Pathway Choices in CRISPR-Cas9-Mediated Genome Editing

    • Chaoyou Xue,
    • Eric C. Greene
    Many clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-based genome editing technologies take advantage of Cas nucleases to induce DNA double-strand breaks (DSBs) at desired locations within a genome. Further processing of the DSBs by the cellular DSB repair machinery is then necessary to introduce desired mutations, sequence insertions, or gene deletions. Thus, the accuracy and efficiency of genome editing are influenced by the cellular DSB repair pathways.

Reviews

    Featured Article
  • To NMD or Not To NMD: Nonsense-Mediated mRNA Decay in Cancer and Other Genetic Diseases

    • Fran Supek,
    • Ben Lehner,
    • Rik G.H. Lindeboom
    The nonsense-mediated mRNA decay (NMD) pathway degrades some but not all mRNAs bearing premature termination codons (PTCs). Decades of work have elucidated the molecular mechanisms of NMD. More recently, statistical analyses of large genomic datasets have allowed the importance of known and novel 'rules of NMD' to be tested and combined into methods that accurately predict whether PTC-containing mRNAs are degraded or not. We discuss these genomic approaches and how they can be applied to identify diseases and individuals that may benefit from inhibition or activation of NMD.
  • The PDE-Opathies: Diverse Phenotypes Produced by a Functionally Related Multigene Family

    • Graeme B. Bolger
    Open Access
    The phosphodiesterase (PDE)-opathies, an expanding set of disorders caused by germline mutations in cyclic nucleotide PDEs, present an intriguing paradox. The enzymes encoded by the PDE family all hydrolyze cAMP and/or cGMP, but mutations in different family members produce very divergent phenotypes. Three interacting factors have been shown recently to contribute to this phenotypic diversity: (i) the 21 genes encode over 80 different isoforms, using alternative mRNA splicing and related mechanisms; (ii) the various isoforms have different regulatory mechanisms, mediated by their unique amino-terminal regulatory domains; (iii) the isoforms differ widely in their pattern of tissue expression.

Genome of the Month

  • Mammuthus sp. (Early and Middle Pleistocene Mammoths)

    • Patrícia Pečnerová,
    • David Díez-del-Molino,
    • Tom van der Valk,
    • Marianne Dehasque,
    • Anders Götherström,
    • Love Dalén
    Open Access
    Mammoths, Mammuthus sp., are iconic megafauna species that came to symbolize the Ice Age. However, the typical Late Pleistocene forms, which we know as the woolly and Columbian mammoths, were only the youngest offshoots on the mammoth evolutionary tree. The time window during which mammoths acquired traits that made them adapted to the cold environment has now become clearer thanks to genomic data from three Early and Middle Pleistocene mammoths. Two of these, identified as steppe-mammoths and called Krestovka and Adycha, lived >1 million years ago (Mya) and represent two independent genetic lineages.
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