Nature2014-06-26 5:49 PM

自闭症和精神分裂症中的基因变异 CNVs conferring risk of autism or schizophrenia affect cognition in controls

论文摘要 

某些罕见的“版本数变异体”(CNVs)(在其中基因组的一些部分是重复的)以前被与精神分裂症和自闭症联系起来,但它们的携带者并不总会患病或有明显智残。Kari Stefansson及同事对来自冰岛的一组这些变异体携带者进行了研究,发现虽然这些人没有病,但他们的脑子与没有携带这些突变的对照组的脑子有微妙差别。并非所有的CNVs都影响相同的认知区域,但其中的一个,即15q11.2(BP1-BP2)删除,影响脑结构的模式与在精神分裂症第一次发病过程中所观察到的模式和诵读困难症的结构关联性模式都是一致的。通过进一步研究这些携带者,也许有可能更精准地确定哪些异常使得携带者有患精神分裂症的风险。

Abstract 

In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNV only confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.

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