Levy Rebecca J, Xu Bin, Gogos Joseph A, Karayiorgou Maria
Department of Psychiatry, Columbia University Medical Center, New York, NY, USA.
Methods Mol Biol. 2012;838:97-113. doi: 10.1007/978-1-61779-507-7_4.
Psychiatric disorders are multifactorial in nature with complex genetic architecture. A number of recent studies, building upon earlier findings of copy number variants (CNVs) at the 22q11.2 locus, suggest that rare CNVs represent an important component of genetic heterogeneity in the etiology of complex psychiatric diseases, such as schizophrenia. De novo CNVs are found with higher frequency among sporadic cases, whereas inherited CNVs are enriched among familial cases. Despite substantial progress, a number of challenges remain, such as pinpointing causative relationships between specific gene(s) affected by CNVs and disease phenotypes as well as distinguishing abnormal structural mutations from neutral polymorphisms and establishing a clear association between individual pathogenic CNV and disease phenotypes.
精神疾病本质上是多因素的，具有复杂的遗传结构。基于先前在22q11.2位点发现的拷贝数变异（CNV）的研究结果，最近的一些研究表明，罕见的CNV是复杂精神疾病（如精神分裂症）病因中遗传异质性的重要组成部分。新发CNV在散发病例中出现的频率更高，而遗传性CNV在家族性病例中更为富集。尽管取得了重大进展，但仍存在一些挑战，例如确定受CNV影响的特定基因与疾病表型之间的因果关系，以及区分异常结构突变与中性多态性，并在个体致病CNV与疾病表型之间建立明确的关联。
