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动物模型中正向遗传学筛选在精神疾病研究中的转化相关性。

Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.

机构信息

School of Biological and Behavioural Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, England, UK.

Department of Biomedical Sciences, University of Padova, Via Ugo Bassi, 58/B, 35131 Padova, Italy.

出版信息

Neurosci Biobehav Rev. 2022 Apr;135:104559. doi: 10.1016/j.neubiorev.2022.104559. Epub 2022 Feb 4.

Abstract

Psychiatric disorders represent a significant burden in our societies. Despite the convincing evidence pointing at gene and gene-environment interaction contributions, the role of genetics in the etiology of psychiatric disease is still poorly understood. Forward genetic screens in animal models have helped elucidate causal links. Here we discuss the application of mutagenesis-based forward genetic approaches in common animal model species: two invertebrates, nematodes (Caenorhabditis elegans) and fruit flies (Drosophila sp.); and two vertebrates, zebrafish (Danio rerio) and mice (Mus musculus), in relation to psychiatric disease. We also discuss the use of large scale genomic studies in human populations. Despite the advances using data from human populations, animal models coupled with next-generation sequencing strategies are still needed. Although with its own limitations, zebrafish possess characteristics that make them especially well-suited to forward genetic studies exploring the etiology of psychiatric disorders.

摘要

精神障碍在我们的社会中造成了重大负担。尽管有令人信服的证据表明基因和基因-环境相互作用的贡献,但遗传在精神疾病病因学中的作用仍知之甚少。动物模型中的正向遗传学筛选有助于阐明因果关系。在这里,我们讨论了基于诱变的正向遗传方法在常见的动物模型物种中的应用:两种无脊椎动物,线虫(秀丽隐杆线虫)和果蝇(黑腹果蝇);两种脊椎动物,斑马鱼(斑马鱼)和老鼠(小家鼠),与精神疾病有关。我们还讨论了在人类群体中使用大规模基因组研究的情况。尽管利用人类群体的数据取得了进展,但仍然需要结合动物模型和下一代测序策略。尽管存在自身的局限性,但斑马鱼具有的特征使它们特别适合于探索精神障碍病因的正向遗传学研究。

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