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

Translational relevance of forward genetic screens in animal models for the study of psychiatric disease.
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远期遗传筛选在动物模型中的转化相关性,用于研究精神病。

DOI:
10.1016/j.neubiorev.2022.104559
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发表时间:
2022-04
影响因子:
8.2
通讯作者:
Brennan, Caroline H.
Brennan, Caroline H.
中科院分区:
医学1区
文献类型:
--
作者:
Sheardown, Eva;Mech, Aleksandra M.;Petrazzini, Maria Elena Miletto;Leggieri, Adele;Gidziela, Agnieszka;Hosseinian, Saeedeh;Sealy, Ian M.;Torres-Perez, Jose, V;Busch-Nentwich, Elisabeth M.;Malanchini, Margherita;Brennan, Caroline H.

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精神疾病是我们社会的一个重大负担。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,遗传学在精神疾病病因学中的作用仍然知之甚少。动物模型中的正向遗传筛查有助于阐明因果关系。本文讨论了基于诱变的正向遗传学方法在两种常见的无脊椎动物模式动物中的应用:线虫(Caushabditis elegans)和果蝇(Drosophila sp.);以及两种脊椎动物,斑马鱼(Danio rerio)和小鼠(Mus musculus),与精神疾病有关。我们还讨论了大规模基因组研究在人群中的应用。尽管使用来自人类群体的数据取得了进展,但仍然需要结合下一代测序策略的动物模型。虽然有其自身的局限性,但斑马鱼具有的特性使其特别适合于探索精神疾病病因的遗传学研究。
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 aetiology 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 aetiology of psychiatric disorders.
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