光学基因组图谱在染色体结构异常检测中的应用

Application of Optical Genome Mapping in the Detection of Chromosome Structural Variations

染色体结构异常(structural variations,SVs)是临床中的常见现象,主要包括染色体缺失、重复、倒位和易位等,因其会引起基因融合、断裂或拷贝数改变,常导致疾病的发生。目前临床上对于SVs的检测多采用染色体核型、芯片分析或高通量测序等细胞遗传学或常规分子遗传学技术。近年来,随着检测技术的不断发展,隐匿性染色体平衡易位和微小片段的异常在产前诊断、新生儿遗传病、血液病及肿瘤等研究领域逐渐被重视,而传统的遗传学检测方法存在较为明显的局限性。光学基因组图谱(optical genome mapping,OGM)是近年来基于全新原理开发的分子遗传学检测技术,与传统技术相比,其对常规和隐匿性SVs(平衡易位、微小片段等)都有较强的检出能力,在多领域有较高的应用价值。但是OGM也存在一定的局限性,如其因灵敏度较高而需要其他手段辅助排除假阳性结果,在近着丝粒等无标记区域无法进行检测等。本文针对传统细胞遗传学检测技术和OGM对SVs的检测能力,OGM的优势、缺陷及其在肿瘤、儿科等领域的应用进行综述。

Chromosome structural variations(SVs)are the common clinical phenomenon,which mainly includes chromosome deletion,repetition,inversion and translocation,because it can cause gene fusion,interruption or copy number changes,which often lead to disease.At present,cytogenetic or traditional molecular genetics technologies such as chromosome karyotyping,chip analysis or high-throughput sequencing are often used to detect SVs in clinic.In recent years,with the continuous development of detection technology,the abnormalities of occult chromosome balanced translocation and tiny fragments have been paid more and more attention in the research fields of prenatal diagnosis,neonatal hereditary diseases,blood disease,tumors and so on.The limitations of traditional genetic detection methods have prominent limitations.Optical genome mapping(OGM)is a molecular genetic detection technology developed based on a new principle in recent years.Compared with traditional technologies,it has stronger detection ability for both conventional and occult SVs(chromosome balanced translocation and tiny fragments,etc),and has high application value in many fields.However,OGM also has certain limitations,such as its high sensitivity,requiring other means to eliminate false positive results,and cannot be detected in unlabeled areas such as near centromere.This review wll analyze the traditional cytogenetic detection techniques and the ability of OGM to detect SVs,as well as the advantages,disadvantages and application in pediatrics and tumor diagnosis of OGM.