Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH.
Comparative analysis of copy number detection by whole-genome BAC and oligonucleotide array CGH.
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DOI：
10.1186/1755-8166-3-11
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发表时间：
2010-06-29
影响因子：
1.3
通讯作者：
Ballif BC
中科院分区：
文献类型：
--
作者：
Neill NJ;Torchia BS;Bejjani BA;Shaffer LG;Ballif BC
基于微阵列的比较基因组杂交（aCGH）是用于检测与染色体异常相关的DNA拷贝数增加和丢失的强有力的诊断工具，其中许多染色体异常低于常规染色体分析的分辨率。据推测，全基因组寡核苷酸（oligo）阵列比全基因组细菌人工染色体（BAC）阵列识别出更多临床显著的拷贝数异常，但这尚未在临床诊断环境中进行系统研究。为了确定相似设计的BAC和寡核苷酸芯片之间的检测率差异，我们开发了全基因组BAC和寡核苷酸芯片，并在提交给我们实验室进行aCGH的466份连续临床标本的并排比较中对其进行了验证。在研究的466例病例中，67例（14.3%）具有通过全基因组BAC阵列检测到的潜在临床意义的拷贝数失衡，73例（15.6%）具有通过全基因组寡核苷酸阵列检测到的潜在临床意义的拷贝数失衡。然而，由于两个平台都鉴定出了临床意义不明确的拷贝数变异，我们设计了一种系统性方法来解释拷贝数变异，并通过BAC阵列检测了另外3，443例病例，通过寡核苷酸阵列检测了另外3，096例病例。在BAC芯片检测的病例中，发现17.6%的病例具有潜在临床意义的拷贝数异常，而寡核苷酸芯片检测的病例检出率增加到22.5%。此外，我们验证了用于检测镶嵌现象的寡核苷酸阵列，并发现它可以常规检测30%或更高水平的镶嵌现象。虽然BAC阵列具有更快的周转时间，但寡核苷酸阵列的检测率增加使得它们对于临床细胞遗传学测试具有吸引力。
Microarray-based comparative genomic hybridization (aCGH) is a powerful diagnostic tool for the detection of DNA copy number gains and losses associated with chromosome abnormalities, many of which are below the resolution of conventional chromosome analysis. It has been presumed that whole-genome oligonucleotide (oligo) arrays identify more clinically significant copy-number abnormalities than whole-genome bacterial artificial chromosome (BAC) arrays, yet this has not been systematically studied in a clinical diagnostic setting. To determine the difference in detection rate between similarly designed BAC and oligo arrays, we developed whole-genome BAC and oligonucleotide microarrays and validated them in a side-by-side comparison of 466 consecutive clinical specimens submitted to our laboratory for aCGH. Of the 466 cases studied, 67 (14.3%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome BAC array, and 73 (15.6%) had a copy-number imbalance of potential clinical significance detectable by the whole-genome oligo array. However, because both platforms identified copy number variants of unclear clinical significance, we designed a systematic method for the interpretation of copy number alterations and tested an additional 3,443 cases by BAC array and 3,096 cases by oligo array. Of those cases tested on the BAC array, 17.6% were found to have a copy-number abnormality of potential clinical significance, whereas the detection rate increased to 22.5% for the cases tested by oligo array. In addition, we validated the oligo array for detection of mosaicism and found that it could routinely detect mosaicism at levels of 30% and greater. Although BAC arrays have faster turnaround times, the increased detection rate of oligo arrays makes them attractive for clinical cytogenetic testing.
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DOI：
10.1007/978-1-60761-663-4_8
发表时间：
2010-01-01
期刊：
MICROARRAY METHODS FOR DRUG DISCOVERY
影响因子：
--
作者：
Bejjani, Bassem A.;Shaffer, Lisa G.;Ballif, Blake C.
通讯作者：
Ballif, Blake C.
影响因子：
4.8
作者：
Gropman, Andrea L.;Elsea, Sarah;Smith, Ann C. M.
通讯作者：
Smith, Ann C. M.
影响因子：
1.7
作者：
Bailey, J. A.;Kidd, J. M.;Eichler, E. E.
通讯作者：
Eichler, E. E.
影响因子：
30.8
作者：
Sharp, Andrew J.;Hansen, Sierra;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
9.8
作者：
Miller, David T.;Adam, Margaret P.;Ledbetter, David H.
通讯作者：
Ledbetter, David H.