miRNA-mediated risk for schizophrenia in 22q11.2 deletion syndrome.
miRNA-mediated risk for schizophrenia in 22q11.2 deletion syndrome.
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DOI：
10.3389/fgene.2012.00291
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发表时间：
2012
影响因子：
3.7
通讯作者：
Bassett AS
中科院分区：
文献类型：
--
作者：
Brzustowicz LM;Bassett AS
在人类中，最常见的基因组疾病是22q11.2染色体1.5 - 3mb区域的半合子缺失。由此产生的22q11.2缺失综合征（22q11.2 ds）可影响多器官系统，最明显的包括心脏、颅面和神经发育缺陷。与普通人群相比，患有22q11.2DS的个体患精神分裂症的风险是普通人群的20 - 25倍，这使得22q11.2DS成为已知最强的精神分裂症分子遗传风险因素。尽管缺失的区域包括DGCR8，一种编码miRNA加工蛋白的基因，但这种缺失增加风险的确切机制尚不清楚。重要的是，有几条证据表明，mirna可能会调节其他非22q11.2 ds人群患精神分裂症的风险。在这里，我们提出了一种理论，从机制上解释了22q11.2DS、mirna和精神分裂症风险之间的联系。我们概述了由这一理论产生的可测试的预测，并提出了支持我们模型的初步数据。该模型的进一步实验验证可以为22q11.2DS和更常见形式的精神分裂症的病因提供重要的见解。
In humans, the most common genomic disorder is a hemizygous deletion of a 1.5–3 Mb region of chromosome 22q11.2. The resultant 22q11.2 deletion syndrome (22q11.2DS) can affect multiple organ systems, and most notably includes cardiac, craniofacial, and neurodevelopmental defects. Individuals with 22q11.2DS have a 20–25-fold risk of developing schizophrenia compared to individuals from the general population, making 22q11.2DS the strongest known molecular genetic risk factor for schizophrenia. Although the deleted region includes DGCR8, a gene coding for a miRNA processing protein, the exact mechanism by which this deletion increases risk is unknown. Importantly, several lines of evidence suggest that miRNAs may modulate risk for schizophrenia in other, non-22q11.2DS populations. Here we present a theory which mechanistically explains the link between 22q11.2DS, miRNAs, and schizophrenia risk. We outline the testable predictions generated by this theory and present preliminary data in support of our model. Further experimental validation of this model could provide important insights into the etiology of both 22q11.2DS and more common forms of schizophrenia.