Rare Coding Variants at Microdeletion Regions and Schizophrenia Susceptibility

描述（由申请人提供）：众所周知，新生微缺失在精神分裂症和自闭症等神经精神特征的易感性中起作用。然而，大多数基因组变异（包括微缺失）是遗传的，并不代表从头开始的事件。然而，来自大型研究的证据表明，患者中罕见基因组缺失的发生率更高，而我们知道，同样的变异也可能存在于未受影响的受试者中，包括患者的亲属。我们自己的研究结果表明，在某些情况下，大的基因组缺失可能会在剩余的等位基因上发现隐性的、功能性的变异。我们假设精神分裂症患者的非缺失等位基因可能与未受影响的受试者的非缺失等位基因相比富含影响基因功能的变异。为了进一步探讨这一点，我们将收集250例精神分裂症患者和250例未受拷贝数变异数据影响的对照组中受基因组缺失影响的基因编码区域的序列数据。

DESCRIPTION (provided by applicant): It is known that de novo microdeletions play a role in the susceptibility of neuropsychiatric traits such as schizophrenia and autism. However, the majority of the genomic variation (including microdeletions) is inherited and does not represent de novo events. Evidence from large studies, however, points to a higher incidence of rare genomic deletions in patients, while we know that the same variants may also be present in unaffected subjects including relatives of patients. Our own findings suggest that there are cases in which large genomic deletions may uncover recessive, functional variants at the remaining allele. We hypothesize that the non-deleted alleles in schizophrenia patients may be enriched with variants affecting gene function compared to non-deleted alleles present in unaffected subjects. To explore this further, we will collect sequence data of coding regions of genes that are affected by genomic deletions in 250 schizophrenia cases and 250 unaffected controls for which copy number variation data is available.