Lichter P, Cremer T, Tang C J, Watkins P C, Manuelidis L, Ward D C
Department of Human Genetics, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9664-8. doi: 10.1073/pnas.85.24.9664.
Plasmid clones containing up to 94 kilobases of single-copy DNA from band q22.3 of chromosome 21 and a complete pool of insert DNA from a chromosome 21 recombinant library have been used to rapidly detect numerical and structural aberrations of chromosome 21 by in situ hybridization in both metaphase and interphase cells. A trisomic karyotype, diagnostic of Down syndrome, is readily detected in nonmitotic cells because the majority of their nuclei exhibit three discrete foci of hybridization, in contrast to normal diploid cells, which show two foci. Chromosomal translocations involving chromosome 21 sequences were also detected with these probes, and the intranuclear location of 21q22.3 DNA sequences in "normal" human brain neurons was established with the plasmid DNA probe set. These results suggest that chromosome 21-specific probes may have utility in clinical diagnostics, especially by facilitating the direct analysis of interphase cells.
含有来自21号染色体q22.3带长达94千碱基对单拷贝DNA的质粒克隆以及来自21号染色体重组文库的完整插入DNA库，已被用于通过中期和间期细胞原位杂交快速检测21号染色体的数目和结构畸变。在非有丝分裂细胞中很容易检测到诊断唐氏综合征的三体核型，因为与显示两个杂交位点的正常二倍体细胞相比，它们大多数细胞核呈现三个离散的杂交位点。利用这些探针还检测到了涉及21号染色体序列的染色体易位，并用质粒DNA探针组确定了“正常”人类脑神经元中21q22.3 DNA序列的核内定位。这些结果表明，21号染色体特异性探针可能在临床诊断中有用，特别是通过促进间期细胞的直接分析。
