Ahn Joo Wook, Mann Kathy, Walsh Sally, Shehab Marwa, Hoang Sarah, Docherty Zoe, Mohammed Shehla, Mackie Ogilvie Caroline
Cytogenetics Department, Guy's & St Thomas' NHS Foundation Trust, London SE1 9RT, UK.
Mol Cytogenet. 2010 Apr 15;3:9. doi: 10.1186/1755-8166-3-9.
Several studies have demonstrated that array comparative genomic hybridisation (CGH) for genome-wide imbalance provides a substantial increase in diagnostic yield for patients traditionally referred for karyotyping by G-banded chromosome analysis. The purpose of this study was to demonstrate the feasibility of and strategies for, the use of array CGH in place of karyotyping for genome imbalance, and to report on the results of the implementation of this approach.
Following a validation period, an oligoarray platform was chosen. In order to minimise costs and increase efficiency, a patient/patient hybridisation strategy was used, and analysis criteria were set to optimise detection of pathogenic imbalance. A customised database application with direct links to a number of online resources was developed to allow efficient management and tracking of patient samples and facilitate interpretation of results. Following introduction into our routine diagnostic service for patients with suspected genome imbalance, array CGH as a follow-on test for patients with normal karyotypes (n = 1245) and as a first-line test (n = 1169) gave imbalance detection rates of 26% and 22% respectively (excluding common, benign variants). At least 89% of the abnormalities detected by first line testing would not have been detected by standard karyotype analysis. The average reporting time for first-line tests was 25 days from receipt of sample.
Array CGH can be used in a diagnostic service setting in place of G-banded chromosome analysis, providing a more comprehensive and objective test for patients with suspected genome imbalance. The increase in consumable costs can be minimised by employing appropriate hybridisation strategies; the use of robotics and a customised database application to process multiple samples reduces staffing costs and streamlines analysis, interpretation and reporting of results. Array CGH provides a substantially higher diagnostic yield than G-banded chromosome analysis, thereby alleviating the burden of further clinical investigations.
多项研究表明，用于全基因组失衡检测的阵列比较基因组杂交（array CGH）技术能显著提高传统上通过G带染色体分析进行核型分析的患者的诊断率。本研究的目的是证明使用阵列CGH替代核型分析检测基因组失衡的可行性和策略，并报告该方法实施的结果。
经过验证期后，选择了一种寡核苷酸阵列平台。为了降低成本并提高效率，采用了患者/患者杂交策略，并设定了分析标准以优化对致病性失衡的检测。开发了一个与多个在线资源直接链接的定制数据库应用程序，以实现对患者样本的高效管理和跟踪，并便于结果解读。在引入我们针对疑似基因组失衡患者的常规诊断服务后，阵列CGH作为核型正常患者（n = 1245）的后续检测以及作为一线检测（n = 1169），失衡检测率分别为26%和22%（不包括常见的良性变异）。一线检测发现的至少89%的异常无法通过标准核型分析检测到。一线检测的平均报告时间为从收到样本起25天。
阵列CGH可用于诊断服务中替代G带染色体分析，为疑似基因组失衡的患者提供更全面、客观的检测。通过采用适当的杂交策略可将耗材成本的增加降至最低；使用机器人技术和定制数据库应用程序处理多个样本可降低人员成本，并简化结果的分析、解读和报告。与G带染色体分析相比，阵列CGH提供了显著更高的诊断率，从而减轻了进一步临床检查的负担。
