Rare Coding Variants at Microdeletion Regions and Schizophrenia Susceptibility

描述(由申请人提供)：已知从头开始微缺失在精神分裂症和自闭症等神经精神病学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，患者中罕见的基因组缺失的发生率更高，而我们知道，相同的变异也可能存在于包括患者亲属在内的未受影响的受试者中。我们自己的发现表明，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变异。我们假设精神分裂症患者的非缺失等位基因可能富含影响基因功能的变异，而不是未受影响的受试者中存在的非缺失等位基因。为了进一步探索这一点，我们将收集250例精神分裂症患者和250例有拷贝数变异数据的未受影响的对照的基因编码区的序列数据。 公共卫生相关性：精神分裂症是一种可遗传的疾病，但人们对哪些基因在疾病易感性中发挥重要作用知之甚少。这项研究探索了患者与未受影响的个体中影响基因功能的罕见DNA突变的比率。

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. PUBLIC HEALTH RELEVANCE: Schizophrenia is a heritable disease but little is known about which genes play important roles in disease susceptibility. This study explores the rate of rare DNA mutations affecting gene function in patients versus unaffected individuals.