The power of mouse models in the diagnostic odyssey of patients with rare congenital anomalies.

IF 2.7 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
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.

小鼠模型在罕见先天性异常患者诊断中的作用。
先天性畸形是指出生时存在的结构或功能异常,可由遗传或环境影响引起。基因组测序的可用性大大增加了我们对先天性异常的了解,但将变异鉴定与功能相关性和明确诊断联系起来仍然具有挑战性。许多基因具有未知或知之甚少的功能,并且由于缺乏明确的基因型与表型之间的相关性,因此很难从变异发现转向诊断。因此,对于大多数先天性异常,仍然存在一个“诊断的奥德赛”,这给患者、家庭和社会带来了巨大的负担。动物模型在基因发现过程中是必不可少的,因为它们允许研究人员在完整的生物体中验证候选基因的功能和疾病进展。然而,由于有效生成临床相关动物的复杂性,先进模型系统的使用仍然受到限制。在这里,我们重点关注精确工程小鼠在变异到功能研究中的使用,以解决分子诊断和创建先天性异常的强大临床前模型,涵盖基因组学,基因组编辑和表型方法的进展,以及未来倡议将动物建模与深度患者多模态数据集相结合的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mammalian Genome
Mammalian Genome 生物-生化与分子生物学
CiteScore
4.00
自引率
0.00%
发文量
33
审稿时长
6-12 weeks
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.
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