Representational oligonucleotide microarray analysis: A high-resolution method to detect genome copy number variation
Representational oligonucleotide microarray analysis: A high-resolution method to detect genome copy number variation
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DOI：
10.1101/gr.1349003
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发表时间：
2003-10-01
期刊：
影响因子：
7
通讯作者：
Wigler, M
中科院分区：
文献类型：
--
作者：
Lucito, R;Healy, J;Wigler, M
我们开发了一种方法，我们称之为ROMA（代表性寡核苷酸微阵列分析），用于检测癌症和正常人类的基因组畸变。通过排列从人类基因组序列设计的寡核粒探针，并与来自癌症和正常细胞的“表征”杂交，我们检测基因组中“拷贝数”改变的区域。我们在整个基因组中实现了平均30 kb的分辨率，并且每15 kb的分辨率高达一个探针是可行的。我们说明了阵列上探头的特点和使用ROMA获得的测量精度。使用这种方法，我们确定了癌症和正常基因组之间以及正常人类基因组之间的差异。在癌症基因组中，我们很容易检测到扩增和大小纯合子和半合子缺失。在正常的人类基因组中，我们经常检测到大的（100 kb到1 Mb）缺失或重复。其中许多变化都包含已知的基因。ROMA将协助发现在癌症中起重要作用的基因和标记，以及在遗传疾病倾向中可能起重要作用的位点。
We have developed a methodology we call ROMA (representational oligonucleotide microarray analysis), for the detection of the genomic aberrations in cancer and normal humans. By arraying oligonucleoticle probes designed from the human genome sequence, and hybridizing with "representations" from cancer and normal cells, we detect regions of the genome with altered "copy number." We achieve an average resolution of 30 kb throughout the genome, and resolutions as high as a probe every 15 kb are practical. We illustrate the characteristics of probes on the array and accuracy of measurements obtained using ROMA. Using this methodology, we identify variation between cancer and normal genomes, as well as between normal human genomes. In cancer genomes, we readily detect amplifications and large and small homozygous and hemizygous deletions. Between normal human genomes, we frequently detect large (100 kb to I Mb) deletions or duplications. Many of these changes encompass known genes. ROMA will assist in the discovery of genes and markers important in cancer, and the discovery of loci that may be important in inherited predispositions to disease.