Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Psychiatry Res. 2019 May;275:94-99. doi: 10.1016/j.psychres.2019.03.019. Epub 2019 Mar 14.
The maternally expressed imprinted gene UBE3A has been implicated in autism, schizophrenia and psychosis. The phenotype of Angelman syndrome, caused by loss of UBE3A expression, involves autism spectrum traits, while Prader-Willi syndrome, where the genotype of maternal disomy increases dosage of UBE3A, shows high penetrance for the development of psychosis. Maternal duplications of the 15q11-q13 chromosome region that overlap the imprinted region also show an association with schizophrenia, further implying a connection between increased dosage of UBE3A and the development of schizophrenia and psychosis. We phenotyped a large population of typical individuals for autism spectrum and schizotypal traits and genotyped them for a set of SNPs in UBE3A. Genetic variation of rs732739, an intronic SNP tagging a large haplotype spanning nearly the entire range of UBE3A, was significantly associated with variation in total schizotypy. Our results provide an independent line of evidence, connecting the imprinted UBE3A gene to the schizophrenia spectrum.
母系表达的印记基因 UBE3A 与自闭症、精神分裂症和精神病有关。由于 UBE3A 表达缺失而导致的 Angelman 综合征的表型涉及自闭症谱系特征，而 Prader-Willi 综合征中母源二倍体的基因型增加了 UBE3A 的剂量，表现出精神病发展的高穿透性。重叠印记区域的 15q11-q13 染色体区域的母体重复也与精神分裂症有关，进一步表明 UBE3A 剂量增加与精神分裂症和精神病的发展之间存在联系。我们对一大群具有自闭症谱系和精神分裂症特征的典型个体进行了表型分析，并对 UBE3A 的一组 SNP 进行了基因分型。rs732739 的遗传变异，一个内含子 SNP 标记了横跨 UBE3A 几乎整个范围的大单倍型，与总精神分裂症特征的变异显著相关。我们的结果提供了独立的证据，将印记基因 UBE3A 与精神分裂症谱系联系起来。
