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Current Issue of Trends in Genetics


Issue: Trends in Genetics

Nov 01, 2021

Volume 37Issue 11p951-1046, e1-e2
Polygenic score is a predictor of an individual's genetic predisposition to a disease or a diseaserelated complex trait. This score is important for disease screening, early intervention, and the development of precision medicine. Polygenic scores are constructed by statistical methods that can take advantage of the polygenic and omnigenic architecture underlying common diseases. On pages 995–1011 in this issue, Ma and Zhou discuss an array of statistical methods recently developed for constructing polygenic scores and how these methods have catalyzed the applications of polygenic scores in genetics and clinics. They highlight a common modeling theme underlying polygenic score methods that largely determines the accuracy of polygenic scores, motivating future methodological development for propelling the field forward. The cover shows the latent distribution of polygenic scores underlying disease status and the combination of genetic assay and statistical modeling that together adapts polygenic scores towards clinical applications, benefiting multiple genetic ancestries across the globe. Image credit: Ying Ma....
Polygenic score is a predictor of an individual's genetic predisposition to a disease or a diseaserelated complex trait. This score is important for disease screening, early intervention, and the development of precision medicine. Polygenic scores are constructed by statistical methods that can take advantage of the polygenic and omnigenic architecture underlying common diseases. On pages 995–1011 in this issue, Ma and Zhou discuss an array of statistical methods recently developed for constructing polygenic scores and how these methods have catalyzed the applications of polygenic scores in genetics and clinics. They highlight a common modeling theme underlying polygenic score methods that largely determines the accuracy of polygenic scores, motivating future methodological development for propelling the field forward. The cover shows the latent distribution of polygenic scores underlying disease status and the combination of genetic assay and statistical modeling that together adapts polygenic scores towards clinical applications, benefiting multiple genetic ancestries across the globe. Image credit: Ying Ma.

Science & Society

  • The Genetic Discrimination Observatory: confronting novel issues in genetic discrimination

    • Yann Joly,
    • Katherine Huerne,
    • Mykhailo Arych,
    • Yvonne Bombard,
    • Aisling De Paor,
    • Edward S. Dove,
    • Palmira Granados Moreno,
    • Calvin W.L. Ho,
    • Chih-Hsing Ho,
    • Ine Van Hoyweghen,
    • Hannah Kim,
    • Audrey Lebret,
    • Timo Minssen,
    • Katharina Ó. Cathaoir,
    • Anya E.R. Prince,
    • Athira P.S. Nair,
    • Margaret Otlowski,
    • Michael S. Pepper,
    • Rob Sladek,
    • Lingqiao Song,
    • Torsten H. Voigt,
    • Ma’n H. Zawati,
    • Gratien Dalpé
    • on behalf of the Genetic Discrimination Observatory (GDO)
    Genetic discrimination (GD) is the differential or unfair profiling of an individual on the basis of genetic data. This article summarizes the actions of the Genetic Discrimination Observatory (GDO) in addressing GD and recent developments in GD since late 2020. It shows how GD can take many forms in today’s rapidly evolving society.

Spotlight

  • Editing the plastid genome of recalcitrant plant species

    • Niaz Ahmad,
    • Brent L. Nielsen,
    • Shahid Mansoor
    Transformation of the chloroplast genome offers key advantages over traditional methods for generating transgenic plants, but this approach is limited to a few plant species. Nakazato et al. have developed a novel technique that will help to extend the technology to other plant species that are recalcitrant to current tissue culture-based chloroplast transformation protocols.

Forum

  • Tissue specificity of DNA repair: the CRISPR compass

    • Joana Ferreira da Silva,
    • Mathilde Meyenberg,
    • Joanna I. Loizou
    Open Access
    CRISPR-Cas9-mediated genome editing holds great promise for the correction of pathogenic variants in humans. However, its therapeutic implementation is hampered due to unwanted editing outcomes. A better understanding of cell type- and tissue-specific DNA repair processes will ultimately enable precise control of editing outcomes for safer and effective therapies.
  • MicroRNAs, damage levels, and DNA damage response control

    • Hartwig Visser,
    • Adam D. Thomas
    DNA damage–inducible miRNAs are likely to be functional in the DNA damage response. This response can elicit damage resolution and cell survival or apoptosis. The current, albeit incomplete, picture suggests that miRNAs can affect cell fate via modulation of key response proteins, but the question is, who’s in charge?

Opinions

  • Genomic instability signals offer diagnostic possibility in early cancer detection

    • Sarah Killcoyne,
    • Aisha Yusuf,
    • Rebecca C. Fitzgerald
    Emerging evidence from the large numbers of cancer genomes analyzed in recent years indicates that chromosomal instability (CI), a well-established hallmark of cancer cells, is detectable in precancerous lesions. In this opinion, we discuss the association of this instability with tumor progression and cancer risk. We highlight the opportunity that early genomic instability presents for the diagnosis of esophageal adenocarcinoma (EAC) and its precancerous lesion, Barrett’s esophagus (BE). With a growing body of evidence suggesting that only a small pool of cancer-related genes are involved in early tumor development, we argue that general genomic instability may hold greater diagnostic potential for early cancer detection as opposed to the identification of individual mutational biomarkers.
  • Non-homologous end-joining at challenged replication forks: an RNA connection?

    • Charlotte Audoynaud,
    • Stéphan Vagner,
    • Sarah Lambert
    Defective DNA replication, known as ‘replication stress’, is a source of DNA damage, a hallmark of numerous human diseases, including cancer, developmental defect, neurological disorders, and premature aging. Recent work indicates that non-homologous end-joining (NHEJ) is unexpectedly active during DNA replication to repair replication-born DNA lesions and to safeguard replication fork integrity. However, erroneous NHEJ events are deleterious to genome stability. RNAs are novel regulators of NHEJ activity through their ability to modulate the assembly of repair complexes in trans.
  • HMGs as rheostats of chromosomal structure and cell proliferation

    • Argyris Papantonis
    High mobility group proteins (HMGs) are the most abundant nuclear proteins next to histones and are robustly expressed across tissues and organs. HMGs can uniquely bend or bind distorted DNA, and are central to such processes as transcription, recombination, and DNA repair. However, their dynamic association with chromatin renders capturing HMGs on chromosomes challenging. Recent work has changed this and now implicates these factors in spatial genome organization. Here, I revisit older and review recent literature to describe how HMGs rewire spatial chromatin interactions to sustain homeostasis or promote cellular aging.

Feature Review

  • Genetic prediction of complex traits with polygenic scores: a statistical review

    • Ying Ma,
    • Xiang Zhou
    Accurate genetic prediction of complex traits can facilitate disease screening, improve early intervention, and aid in the development of personalized medicine. Genetic prediction of complex traits requires the development of statistical methods that can properly model polygenic architecture and construct a polygenic score (PGS). We present a comprehensive review of 46 methods for PGS construction. We connect the majority of these methods through a multiple linear regression framework which can be instrumental for understanding their prediction performance for traits with distinct genetic architectures.

Reviews

  • Navigating the DNA methylation landscape of cancer

    • Atsuya Nishiyama,
    • Makoto Nakanishi
    Open Access
    DNA methylation is a chemical modification that defines cell type and lineage through the control of gene expression and genome stability. Disruption of DNA methylation control mechanisms causes a variety of diseases, including cancer. Cancer cells are characterized by aberrant DNA methylation (i.e., genome-wide hypomethylation and site-specific hypermethylation), mainly targeting CpG islands in gene expression regulatory elements. In particular, the early findings that a variety of tumor suppressor genes (TSGs) are targets of DNA hypermethylation in cancer led to the proposal of a model in which aberrant DNA methylation promotes cellular oncogenesis through TSGs silencing.
  • APOBECs orchestrate genomic and epigenomic editing across health and disease

    • Karla Cervantes-Gracia,
    • Anna Gramalla-Schmitz,
    • Julian Weischedel,
    • Richard Chahwan
    Open Access
    APOBEC proteins can deaminate cytosine residues in DNA and RNA. This can lead to somatic mutations, DNA breaks, RNA modifications, or DNA demethylation in a selective manner. APOBECs function in various cellular compartments and recognize different nucleic acid motifs and structures. They orchestrate a wide array of genomic and epigenomic modifications, thereby affecting various cellular functions positively or negatively, including immune editing, viral and retroelement restriction, DNA damage responses, DNA demethylation, gene expression, and tissue homeostasis.

Genome of the Month

  • Symbiodinium microadriaticum (coral microalgal endosymbiont)

    • Christian R. Voolstra,
    • Manuel Aranda,
    • Ye Zhan,
    • Job Dekker
    Photosynthetic microalgae, from the family Symbiodiniaceae, engage in endosymbioses with marine invertebrates, including stony corals. More generally, dinoflagellates are ubiquitous protists and the main primary producers in the oceans. Despite their ecological and economic importance, their biology remains enigmatic. Here we assembled 94 chromosome-scale scaffolds of the ancestral Symbiodiniaceae species Symbiodinium microadriaticum. Contrary to the random order of genes typically found in eukaryotic cells, genes are enriched toward the ends of chromosomes in alternating unidirectional blocks that are sometimes enriched for genes of specific biological processes.

Correction

  • Ginkgo biloba

    • Yanmei Chen,
    • Chunxiang Fu,
    • Zhenying Wu,
    • Huimin Xu,
    • Hongmei Liu,
    • Harald Schneider,
    • Jinxing Lin
    Errors in the time scale below the tree of the first figure have been corrected.
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Trends in Genetics