Stephen R F Twigg, Nicholas D E Greene, Deborah J Henderson, Pleasantine Mill, Karen J Liu
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引用次数: 0
Abstract
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.
期刊介绍:
Mammalian Genome focuses on the experimental, theoretical and technical aspects of genetics, genomics, epigenetics and systems biology in mouse, human and other mammalian species, with an emphasis on the relationship between genotype and phenotype, elucidation of biological and disease pathways as well as experimental aspects of interventions, therapeutics, and precision medicine. The journal aims to publish high quality original papers that present novel findings in all areas of mammalian genetic research as well as review articles on areas of topical interest. The journal will also feature commentaries and editorials to inform readers of breakthrough discoveries as well as issues of research standards, policies and ethics.