Hacia J G, Brody L C, Chee M S, Fodor S P, Collins F S
National Center for Human Genome Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Genet. 1996 Dec;14(4):441-7. doi: 10.1038/ng1296-441.
The ability to scan a large gene rapidly and accurately for all possible heterozygous mutations in large numbers of patient samples will be critical for the future of medicine. We have designed high-density arrays consisting of over 96,600 oligonucleotides 20-nucleotides (nt) in length to screen for a wide range of heterozygous mutations in the 3.45-kilobases (kb) exon 11 of the hereditary breast and ovarian cancer gene BRCA1. Reference and test samples were co-hybridized to these arrays and differences in hybridization patterns quantitated by two-colour analysis. Fourteen of fifteen patient samples with known mutations were accurately diagnosed, and no false positive mutations were identified in 20 control samples. Eight single nucleotide polymorphisms were also readily detected. DNA chip-based assays may provide a valuable new technology for high-throughput cost-efficient detection of genetic alterations.
能够快速、准确地在大量患者样本中对一个大基因进行所有可能的杂合突变扫描，这对医学的未来至关重要。我们设计了由超过96,600个长度为20个核苷酸（nt）的寡核苷酸组成的高密度阵列，以筛查遗传性乳腺癌和卵巢癌基因BRCA1的3.45千碱基（kb）外显子11中的多种杂合突变。将参考样本和测试样本共同杂交到这些阵列上，并通过双色分析对杂交模式的差异进行定量。在15个已知突变的患者样本中，有14个被准确诊断，并且在20个对照样本中未发现假阳性突变。还很容易检测到8个单核苷酸多态性。基于DNA芯片的检测方法可能为高通量、低成本检测基因改变提供一种有价值的新技术。
