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Article collection: Towards an atlas of variant effects

Towards an atlas of variant effects hero image © Uta Mackensen

© Uta Mackensen

Bringing function to the genome

Multiplexed Assays of Variant Effect (MAVEs) can measure the functional consequences of genetic variants at a scale, allowing the construction of comprehensive variant effect maps for genes and their regulatory elements. These maps are furthering fundamental understanding of how genes and proteins function, as well as enabling precision medicine by revealing the functional impact of variants found in human genomes. This article collection of Genome Biology showcases the power and potential of MAVEs and MAVE data. 

The stage for this collection of articles is set by a short correspondence piece from the Atlas of Variant Effects (AVE) Alliance. In the perspective, the Alliance outlines its vision and specific approach for creating a comprehensive Atlas, which would characterize the function of every possible single nucleotide change in most genes in the human genome.

Peer-review process

Articles published in this collection have undergone the journal’s standard peer-review process and were subject to all of the journal’s standard policies.

  1. Genetic variation in the human genome is a major determinant of individual disease risk, but the vast majority of missense variants have unknown etiological effects. Here, we present a robust learning framewor...

    Authors: Milind Jagota, Chengzhong Ye, Carlos Albors, Ruchir Rastogi, Antoine Koehl, Nilah Ioannidis and Yun S. Song
    Citation: Genome Biology 2023 24:182
  2. Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by mutations in the arylsulfatase A gene (ARSA) and categorized into three subtypes according to age of onset. The functional effect of mo...

    Authors: Marena Trinidad, Xinying Hong, Steven Froelich, Jessica Daiker, James Sacco, Hong Phuc Nguyen, Madelynn Campagna, Dean Suhr, Teryn Suhr, Jonathan H. LeBowitz, Michael H. Gelb and Wyatt T. Clark
    Citation: Genome Biology 2023 24:172
  3. Sequencing has revealed hundreds of millions of human genetic variants, and continued efforts will only add to this variant avalanche. Insufficient information exists to interpret the effects of most variants,...

    Authors: Douglas M. Fowler, David J. Adams, Anna L. Gloyn, William C. Hahn, Debora S. Marks, Lara A. Muffley, James T. Neal, Frederick P. Roth, Alan F. Rubin, Lea M. Starita and Matthew E. Hurles
    Citation: Genome Biology 2023 24:147
  4. Multiplexed assays of variant effect (MAVE) experimentally measure the effect of large numbers of sequence variants by selective enrichment of sequences with desirable properties followed by quantification by ...

    Authors: Charlotte Soneson, Alexandra M. Bendel, Guillaume Diss and Michael B. Stadler
    Citation: Genome Biology 2023 24:132
  5. Glucokinase (GCK) regulates insulin secretion to maintain appropriate blood glucose levels. Sequence variants can alter GCK activity to cause hyperinsulinemic hypoglycemia or hyperglycemia associated with GCK-...

    Authors: Sarah Gersing, Matteo Cagiada, Marinella Gebbia, Anette P. Gjesing, Atina G. Coté, Gireesh Seesankar, Roujia Li, Daniel Tabet, Jochen Weile, Amelie Stein, Anna L. Gloyn, Torben Hansen, Frederick P. Roth, Kresten Lindorff-Larsen and Rasmus Hartmann-Petersen
    Citation: Genome Biology 2023 24:97
  6. Insertions and deletions (indels) enable evolution and cause disease. Due to technical challenges, indels are left out of most mutational scans, limiting our understanding of them in disease, biology, and evol...

    Authors: Christian B. Macdonald, David Nedrud, Patrick Rockefeller Grimes, Donovan Trinidad, James S. Fraser and Willow Coyote-Maestas
    Citation: Genome Biology 2023 24:36
  7. Lynch syndrome (LS) is a cancer predisposition syndrome affecting more than 1 in every 300 individuals worldwide. Clinical genetic testing for LS can be life-saving but is complicated by the heavy burden of va...

    Authors: Anthony Scott, Felicia Hernandez, Adam Chamberlin, Cathy Smith, Rachid Karam and Jacob O. Kitzman
    Citation: Genome Biology 2022 23:266
  8. Multiplex assays of variant effect (MAVEs) are a family of methods that includes deep mutational scanning experiments on proteins and massively parallel reporter assays on gene regulatory sequences. Despite th...

    Authors: Ammar Tareen, Mahdi Kooshkbaghi, Anna Posfai, William T. Ireland, David M. McCandlish and Justin B. Kinney
    Citation: Genome Biology 2022 23:98