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Lookup NU author(s): Professor Deborah HendersonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2025. Congenital anomalies are structural or functional abnormalities present at birth, which can be caused by genetic or environmental influences. The availability of genome sequencing has significantly increased our understanding of congenital anomalies, but linking variant identification to functional relevance and definitive diagnosis remains challenging. Many genes have unknown or poorly understood functions, and with a lack of clear genotype-to-phenotype correlations, it can be difficult to move from variant discovery to diagnosis. Thus, for most congenital anomalies, there still exists a “diagnostic odyssey” which presents a significant burden to patients, families and society. Animal models are essential in the gene discovery process because they allow researchers to validate candidate gene function and disease progression within intact organisms. However, use of advanced model systems continues to be limited due to the complexity of efficiently generating clinically relevant animals. Here we focus on the use of precisely engineered mice in variant-to-function studies for resolving molecular diagnoses and creating powerful preclinical models for congenital anomalies, covering advances in genomics, genome editing and phenotyping approaches as well as the necessity for future initiatives aligning animal modelling to deep patient multimodal datasets.
Author(s): Twigg SRF, Greene NDE, Henderson DJ, Mill P, Liu KJ
Publication type: Article
Publication status: Published
Journal: Mammalian Genome
Year: 2025
Pages: Epub ahead of print
Online publication date: 18/03/2025
Acceptance date: 13/02/2025
Date deposited: 07/04/2025
ISSN (print): 0938-8990
ISSN (electronic): 1432-1777
Publisher: Springer Nature
URL: https://doi.org/10.1007/s00335-025-10114-2
DOI: 10.1007/s00335-025-10114-2
Data Access Statement: No datasets were generated or analysed during the current study.
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