Search for genetic variations conferring risk of schizophrenia by exome sequencing in a Japanese multiplex pedigree

为了确定精神分裂症罕见的渗透风险变异，我们对一个日本多重精神分裂症家系进行了外显子组测序。我们从系谱中获得了6个受影响个体，8个未受影响个体和1个未知情感状态个体的DNA。在两个受影响个体和一个未受影响个体的外显子组测序中，总共调用了302005个序列变异。我们选择了七个假定的功能性错义变异作为精神分裂症的候选风险变异。在Sanger测序证实的4个变异中，UNC13B基因的V1525M变异在家系中与精神分裂症共分离最强烈。这些结果表明，UNC13B V1525M变异是精神分裂症的潜在风险变异。

To identify rare penetrant risk variations for schizophrenia, we performed exome sequencing in a Japanese multiplex schizophrenia pedigree. We obtained DNA from six affected, eight unaffected and one unknown affection status individuals in the pedigree. A total of 302,005 sequence variations were called in the exome sequencing of two affected and one unaffected individuals.We selected seven putatively functional missense variations as candidate risk variations for schizophrenia. Among four variations confirmed by Sanger sequencing, V1525M variation in the UNC13B gene was most strongly cosegregated with schizophrenia in the pedigree. These results suggest that the UNC13B V1525M variation is a potential risk variant for schizophrenia.