en
Scientific article
Review
Open access
English

Genetic cold cases: lessons from solving complex congenital limb disorders

Published inGenes & development, vol. 37, no. 7-8, p. 261-276
Publication date2023-04-01
First online date2023-03-29
Abstract

Congenital genetic disorders affecting limb morphology in humans and other mammals are particularly well described, due to both their rather high frequencies of occurrence and the ease of their detection when expressed as severe forms. In most cases, their molecular and cellular etiology remained unknown long after their initial description, often for several decades, and sometimes close to a century. Over the past 20 yr, however, experimental and conceptual advances in our understanding of gene regulation, in particular over large genomic distances, have allowed these cold cases to be reopened and, eventually, for some of them to be solved. These investigations led not only to the isolation of the culprit genes and mechanisms, but also to the understanding of the often complex regulatory processes that are disturbed in such mutant genetic configurations. Here, we present several cases in which dormant regulatory mutations have been retrieved from the archives, starting from a historical perspective up to their molecular explanations. While some cases remain open, waiting for new tools and/or concepts to bring their investigations to an end, the solutions to others have contributed to our understanding of particular features often found in the regulation of developmental genes and hence can be used as benchmarks to address the impact of noncoding variants in the future.

eng
Keywords
  • Chromatin
  • Congenital disorder
  • Enhancers
  • Limb development
  • Mutations
Citation (ISO format)
ANDREY, Guillaume, DUBOULE, Denis. Genetic cold cases: lessons from solving complex congenital limb disorders. In: Genes & development, 2023, vol. 37, n° 7-8, p. 261–276. doi: 10.1101/gad.350450.123
Main files (1)
Article (Published version)
Identifiers
ISSN of the journal0890-9369
9views
3downloads

Technical informations

Creation05/15/2023 12:27:12 PM
First validation05/23/2023 8:00:55 AM
Update time05/23/2023 8:00:55 AM
Status update05/23/2023 8:00:55 AM
Last indexation08/31/2023 11:16:29 AM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack