How the dosage of a Down syndrome candidate gene affects neural circuitry and behaviour

在唐氏综合症患者中，额外的21号染色体拷贝会增加基因表达，导致大脑缺陷。我们假设一个候选基因Dscam2随着表达的增加而改变其功能。这会导致通常相互粘连的脑细胞相互排斥，导致大脑中不适当的连接。我们将在果蝇身上测试这一模型，并首次展示一种依赖于基因表达的机制，这种机制可能导致唐氏综合症患者的大脑异常。

In Down syndrome, an extra copy of chromosome 21 increases gene expression and leads to brain defects. We hypothesise that one candidate gene, Dscam2, changes its function with increased expression. This causes brain cells that normally stick to each other to repel each other, leading to inappropriate connections in the brain. We will test this model in the fruit fly and demonstrate for the first time a mechanism dependent on gene expression that can lead to brain abnormalities in Down syndrome.