de Leeuw N, Hehir-Kwa J Y, Simons A, Geurts van Kessel A, Smeets D F, Faas B H W, Pfundt R
Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Cytogenet Genome Res. 2011;135(3-4):212-21. doi: 10.1159/000331273. Epub 2011 Sep 16.
Array-based comparative genomic hybridization analysis of genomic DNA was first applied in postnatal diagnosis for patients with intellectual disability (ID) and/or congenital anomalies (CA). Genome-wide single-nucleotide polymorphism (SNP) array analysis was subsequently implemented as the first line diagnostic test for ID/CA patients in our laboratory in 2009, because its diagnostic yield is significantly higher than that of routine cytogenetic analysis. In addition to the detection of copy number variations, the genotype information obtained with SNP array analysis enables the detection of stretches of homozygosity and thereby the possible identification of recessive disease genes, mosaic aneuploidy, or uniparental disomy. Patient-parent (trio) information analysis is used to screen for the presence of any form of uniparental disomy in the patient and can determine the parental origin of a de novo copy number variation. Moreover, the outcome of a genotype analysis is used as a final quality control by ruling out potential sample mismatches due to non-paternity or sample mix-up. SNP array analysis is now also used in our laboratory for patients with disorders for which locus heterogeneity is known (homozygosity pre-screening), in prenatal diagnosis in case of structural ultrasound anomalies, and for patients with leukemia. In this report, we summarize our array findings and experiences in the various diagnostic applications and demonstrate the power of a SNP-based array platform for molecular karyotyping, because it not only significantly improves the diagnostic yield in both constitutional and cancer genome diagnostics, but it also enhances the quality of the diagnostic laboratory workflow.
基于微阵列的基因组DNA比较基因组杂交分析最初应用于智力残疾（ID）和/或先天性异常（CA）患者的产后诊断。随后，全基因组单核苷酸多态性（SNP）阵列分析于2009年在我们实验室作为ID/CA患者的一线诊断测试实施，因为其诊断率明显高于常规细胞遗传学分析。除了检测拷贝数变异外，通过SNP阵列分析获得的基因型信息能够检测纯合性区域，从而可能鉴定隐性疾病基因、嵌合非整倍体或单亲二体。患者-父母（三联体）信息分析用于筛查患者中任何形式的单亲二体的存在，并可确定新生拷贝数变异的亲本来源。此外，基因型分析的结果通过排除由于非父系或样本混淆导致的潜在样本错配，用作最终的质量控制。SNP阵列分析现在也在我们实验室用于已知位点异质性的疾病患者（纯合性预筛查）、结构超声异常情况下的产前诊断以及白血病患者。在本报告中，我们总结了我们在各种诊断应用中的阵列研究结果和经验，并展示了基于SNP的阵列平台在分子核型分析方面的能力，因为它不仅显著提高了体质和癌症基因组诊断的诊断率，还提高了诊断实验室工作流程的质量。
