Application of a target array Comparative Genomic Hybridization to prenatal diagnosis
Application of a target array Comparative Genomic Hybridization to prenatal diagnosis
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DOI：
10.1186/1471-2350-11-102
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发表时间：
2010-06-24
影响因子：
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通讯作者：
Cha, Dong Hyun
中科院分区：
文献类型：
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作者：
Park, Ji Hyeon;Woo, Jung Hoon;Cha, Dong Hyun
背景资料：虽然传统的G显带核型分析仍然是产前遗传诊断的金标准，但阵列比较基因组杂交（阵列CGH）技术在产后遗传诊断中的广泛采用导致了对使用该相同技术进行产前诊断的兴趣越来越大。我们已经调查了我们自己设计的DNA芯片作为产前诊断工具，用于检测亚显微缺失/重复和染色体非整倍性的价值。方法：我们设计了一个目标细菌人工染色体（BAC）为基础的aCGH平台（MacArray（TM）M-chip），专门针对亚显微缺失/重复的26个已知的遗传综合征的医学意义产前观察。为了验证该芯片的有效性，我们从22种遗传病患者的132份参考材料和94份临床穿刺标本中提取基因组DNA进行核型分析。在94例临床样本中，也进行了常规核型分析，3例平衡染色体畸变未检出aCGH。然而，我们确定了8例微缺失的Yq11.23染色体区域，没有发现常规核型分析。该区域含有DAZ基因，缺失可能导致非阻塞性精子发生。结论：我们成功地设计并应用了基于BAC的aCGH产前诊断平台。该平台可与常规核型分析结合使用，并将为靶基因组区域提供快速准确的诊断，同时消除对解释临床不确定基因组区域的需要。
Background: While conventional G-banded karyotyping still remains a gold standard in prenatal genetic diagnoses, the widespread adoption of array Comparative Genomic Hybridization (array CGH) technology for postnatal genetic diagnoses has led to increasing interest in the use of this same technology for prenatal diagnosis. We have investigated the value of our own designed DNA chip as a prenatal diagnostic tool for detecting submicroscopic deletions/duplications and chromosome aneuploidies.Methods: We designed a target bacterial artificial chromosome (BAC)-based aCGH platform (MacArray (TM) M-chip), which specifically targets submicroscopic deletions/duplications for 26 known genetic syndromes of medical significance observed prenatally. To validate the DNA chip, we obtained genomic DNA from 132 reference materials generated from patients with 22 genetic diseases and 94 clinical amniocentesis samples obtained for karyotyping.Results: In the 132 reference materials, all known genomic alterations were successfully identified. In the 94 clinical samples that were also subjected to conventional karyotyping, three cases of balanced chromosomal aberrations were not detected by aCGH. However, we identified eight cases of microdeletions in the Yq11.23 chromosomal region that were not found by conventional karyotyping. This region harbors the DAZ gene, and deletions may lead to non-obstructive spermatogenesis.Conclusions: We have successfully designed and applied a BAC-based aCGH platform for prenatal diagnosis. This platform can be used in conjunction with conventional karyotyping and will provide rapid and accurate diagnoses for the targeted genomic regions while eliminating the need to interpret clinically-uncertain genomic regions.