Microarray comparative genomic hybridization (CGH)-based prenatal diagnosis for chromosome abnormalities using cell-free fetal DNA in amniotic fluid
Microarray comparative genomic hybridization (CGH)-based prenatal diagnosis for chromosome abnormalities using cell-free fetal DNA in amniotic fluid
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DOI：
10.1007/s10038-006-0376-7
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Ishimaru, Tadayuki
中科院分区：
文献类型：
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作者：
Miura, Shoko;Miura, Kiyonori;Ishimaru, Tadayuki
羊水上清液中的游离胎儿DNA(CffDNA)通常被丢弃，可作为产前诊断的样本。为了利用cffDNA快速产前诊断常见的染色体异常，例如13、18和21三体以及X单体，我们开发了一种基于微阵列的靶向比较基因组杂交(CGH)板，在该板上可以发现来自13、18、21、X和Y染色体的BAC克隆。利用未培养羊水中的cffDNA，对13例先天畸形胎儿进行了基因芯片-CGH分析。CffDNA基因芯片CGH在5天内对13个胎儿中的12个进行了成功的分子核型分析。对12例胎儿(13三体1例，18三体2例，21三体2例，X单体1例，正常核型6例)进行了常规培养的羊水细胞染色体分析。基因芯片CGH显示其分子核型正常的1例胎儿实际上存在平衡易位，45，XY，der(14；21)(q10；q10)。结果表明，cffDNA基因芯片CGH是一种有效的妊娠晚期染色体异常的快速产前诊断方法，特别是与羊水培养细胞常规核型分析相结合。
Cell-free fetal DNA (cffDNA) in the supernatant of amniotic fluid, which is usually discarded, can be used as a sample for prenatal diagnosis. For rapid prenatal diagnosis of frequent chromosome abnormalities, for example trisomies 13, 18, and 21, and monosomy X, using cffDNA, we have developed a targeted microarray-based comparative genomic hybridization (CGH) panel on which BAC clones from chromosomes 13, 18, 21, X, and Y were spotted. Microarray-CGH analysis was performed for a total of 13 fetuses with congenital anomalies using cffDNA from their uncultured amniotic fluid. Microarray CGH with cffDNA led to successful molecular karyotyping for 12 of 13 fetuses within 5 days. Karyotypes of the 12 fetuses (one case of trisomy 13, two of trisomy 18, two of trisomy 21, one of monosomy X, and six of normal karyotype) were later confirmed by conventional chromosome analysis using cultured amniocytes. The one fetus whose molecular-karyotype was indicated as normal by microarray CGH actually had a balanced translocation, 45,XY,der(14;21)(q10;q10). The results indicated that microarray CGH with cffDNA is a useful rapid prenatal diagnostic method at late gestation for chromosome abnormalities with copy-number changes, especially when combined with conventional karyotyping of cultured amniocytes.