Association of oligodendrocytes differentiation regulator gene DUSP15 with autism
Association of oligodendrocytes differentiation regulator gene DUSP15 with autism
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少突胶质细胞分化调节基因DUSP15与自闭症的关系
DOI：
10.1080/15622975.2016.1178395
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发表时间：
2017-03-01
影响因子：
3.1
通讯作者：
Zhang, Dai
中科院分区：
文献类型：
--
作者：
Tian, Ye;Wang, Lifang;Zhang, Dai
目的：自闭症是一种广泛性神经发育障碍，具有高遗传性。遗传因素在自闭症的病因学中起着至关重要的作用。双特异性磷酸酶15 （DUSP15）被认为是少突胶质细胞分化的关键调控基因。先前的一项研究在自闭症患者的DUSP15外显子6中发现了一种可能具有有害功能的新生错义变体（p.Thr107Met）。因此，我们对自闭症儿童中的这种突变进行了测序，并进行了DUSP15多态性与自闭症之间的关联分析。方法：我们对255名自闭症儿童和427名健康对照者进行了病例对照研究。选择了4个标签单核苷酸多态性（snp）。这些snp和先前报道的DUSP15外显子6突变通过Sanger测序进行基因分型。结果：rs3746599基因在等位基因、加性基因和显性基因模型下分别与自闭症显著相关（χ2 = 9.699, P = 0.0018; χ2 = 16.224, P = 0.001; χ2 = 7.198, P = 0.007）。在Bonferroni校正和排列检验（n = 10,000）后，这种关联仍然显著。我们没有检测到先前研究报道的错义变体p.s thr107met。然而，在一名自闭症儿童中检测到一种可能具有致病作用的DUSP15 （p.a ala56thr）的新生错义变体，而在健康对照中则不存在。结论：我们的研究结果初步提示DUSP15可能是中国汉族人群自闭症的易感基因。
Abstract Objectives: Autism is a pervasive neurodevelopmental disorder with high heritability. Genetic factors play crucial roles in the aetiology of autism. Dual specificity phosphatase 15 (DUSP15) has been recognised as a key regulator gene for oligodendrocytes differentiation. A previous study detected one de novo missense variant (p.Thr107Met) with probable deleterious function in exon 6 of DUSP15 among patients with autism. Therefore, we sequenced this mutation in autistic children and performed an association analysis between DUSP15 polymorphisms and autism. Methods: We performed a case–control study between 255 children affected with autism and 427 healthy controls. Four tag-single nucleotide polymorphisms (SNPs) were selected. These SNPs and the previously reported mutation in exon 6 of DUSP15 were genotyped via Sanger sequencing. Results: Our results showed that rs3746599 was significantly associated with autism under allelic, additive and dominant models, respectively (χ2 = 9.699, P = 0.0018; χ2 = 16.224, P = 0.001; χ2 = 7.198, P = 0.007). The association remained significant after Bonferroni correction and permutation tests (n = 10,000). We did not detect the missense variant p.Thr107Met reported in previous studies. However, a de novo missense variant of DUSP15 (p.Ala56Thr) with a probable disease-causing effect was detected in one autistic child while absent in healthy controls. Conclusions: Our findings initially suggest that DUSP15 might be a susceptibility gene for autism in Chinese Han population.