Validation of Candidate Sleep Disorder Risk Genes Using Zebrafish.
Validation of Candidate Sleep Disorder Risk Genes Using Zebrafish.
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DOI：
10.3389/fnmol.2022.873520
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发表时间：
2022
影响因子：
4.8
通讯作者：
Prober, David A.
中科院分区：
文献类型：
--
作者：
Tran, Steven;Prober, David A.
睡眠障碍和慢性睡眠障碍是常见的，并与心脏代谢疾病和神经精神疾病有关。在动物模型中已经描述了几种调节睡眠的遗传途径和神经元机制，但人类睡眠变化和睡眠障碍的基因在很大程度上是未知的。识别这些基因对于开发睡眠障碍及其相关合并症的有效疗法至关重要。为了解决这一未解决的健康问题，全基因组关联研究（GWAS）已经确定了许多与人类睡眠特征和睡眠障碍相关的遗传变异。然而，在大多数情况下，尚不清楚哪个基因负责与遗传变异相关的睡眠表型。因此，有必要使用动物模型对通过GWAS鉴定的候选基因进行实验验证。啮齿动物不适合这种奋进，因为它们对高通量睡眠测定的适应性差，以及与产生、维持和测试大量突变株系相关的高成本。斑马鱼（Danio rerio）是一种用于研究睡眠的替代脊椎动物模型，可以使用CRISPR/Cas9系统快速且具有成本效益地产生突变系。然后，可以使用高通量行为测定法平行测试许多斑马鱼突变系，以确定其损失影响睡眠的基因。这个过程确定了与每个GWAS命中相关的基因，该基因可能是人类睡眠表型的原因。这一策略是对GWAS方法的有力补充，并有望确定常见人类睡眠障碍的遗传基础。
Sleep disorders and chronic sleep disturbances are common and are associated with cardio-metabolic diseases and neuropsychiatric disorders. Several genetic pathways and neuronal mechanisms that regulate sleep have been described in animal models, but the genes underlying human sleep variation and sleep disorders are largely unknown. Identifying these genes is essential in order to develop effective therapies for sleep disorders and their associated comorbidities. To address this unmet health problem, genome-wide association studies (GWAS) have identified numerous genetic variants associated with human sleep traits and sleep disorders. However, in most cases, it is unclear which gene is responsible for a sleep phenotype that is associated with a genetic variant. As a result, it is necessary to experimentally validate candidate genes identified by GWAS using an animal model. Rodents are ill-suited for this endeavor due to their poor amenability to high-throughput sleep assays and the high costs associated with generating, maintaining, and testing large numbers of mutant lines. Zebrafish (Danio rerio), an alternative vertebrate model for studying sleep, allows for the rapid and cost-effective generation of mutant lines using the CRISPR/Cas9 system. Numerous zebrafish mutant lines can then be tested in parallel using high-throughput behavioral assays to identify genes whose loss affects sleep. This process identifies a gene associated with each GWAS hit that is likely responsible for the human sleep phenotype. This strategy is a powerful complement to GWAS approaches and holds great promise to identify the genetic basis for common human sleep disorders.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
3.4
作者：
Chen A;Singh C;Oikonomou G;Prober DA
通讯作者：
Prober DA
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
2.6
作者：
Bellipanni, Gianfranco;Rink, Elke;Bally-Cuif, Laure
通讯作者：
Bally-Cuif, Laure
DOI：
10.1073/pnas.0810793106
发表时间：
2009-06-23
影响因子：
11.1
作者：
Alenina, Natalia;Kikic, Dana;Bader, Michael
通讯作者：
Bader, Michael