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Lookup NU author(s): Professor Deborah HendersonORCiD, Ahlam Alqahtani, Dr Bill Chaudhry, Dr Lorraine Eley
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 Company of Biologists Ltd. All rights reserved.Congenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate. However, several other factors are likely to contribute. For example, the level of patient phenotyping required for clinical care may be insufficient for research studies focused on mechanistic discovery. Although several hundred mouse gene knockouts have been described with CHDs, these are generally not phenotyped and described in the same way as CHDs in patients, and thus are not readily comparable. Moreover, most patients with CHDs carry variants of uncertain significance of crucial cardiac genes, further complicating comparisons between humans and mouse mutants. In spite of major advances in cardiac developmental biology over the past 25 years, these advances have not been well communicated to geneticists and cardiologists. As a consequence, the latest data from developmental biology are not always used in the design and interpretation of studies aimed at discovering the genetic causes of CHDs. In this Special Article, while considering other in vitro and in vivo models, we create a coherent framework for accurately modelling and phenotyping human CHDs in mice, thereby enhancing the translation of genetic and genomic studies into the causes of CHDs in patients.
Author(s): Henderson DJ, Alqahtani A, Chaudhry B, Cook A, Eley L, Houyel L, Hughes M, Keavney B, de la Pompa JL, Sled J, Spielmann N, Teboul L, Zaffran S, Mill P, Liu KJ
Publication type: Article
Publication status: Published
Journal: DMM Disease Models and Mechanisms
Year: 2024
Volume: 17
Issue: 11
Print publication date: 01/11/2024
Online publication date: 22/11/2024
Acceptance date: 29/10/2024
Date deposited: 09/12/2024
ISSN (print): 1754-8403
ISSN (electronic): 1754-8411
Publisher: Company of Biologists Ltd
URL: https://doi.org/10.1242/dmm.050913
DOI: 10.1242/dmm.050913
PubMed id: 39575509
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