McDermid H E, Duncan A M, Brasch K R, Holden J J, Magenis E, Sheehy R, Burn J, Kardon N, Noel B, Schinzel A
Science. 1986 May 2;232(4750):646-8. doi: 10.1126/science.3961499.
Most individuals with cat eye syndrome (CES) have a supernumerary bisatellited chromosome which, on the basis of cytogenetic evidence, has been reported to originate from either chromosome 13 or 22. To resolve this question, a single-copy DNA probe, D22S9, was isolated and localized to 22q11 by in situ hybridization to metaphase chromosomes. The number of copies of this sequence was determined in CES patients by means of Southern blots and densitometry analysis of autoradiographs. In patients with the supernumerary chromosome, four copies were found, whereas in one patient with a duplication of part of chromosome 22, there were three copies. Therefore, the syndrome results from the presence of either three or four copies of DNA sequences from 22q11; there is no evidence that sequences from other chromosomes are involved. This work demonstrates how DNA sequence dosage analysis can be used to study genetic disorders that are not readily amenable to standard cytogenetic analysis.
大多数猫眼综合征（CES）患者有一条额外的双随体染色体，根据细胞遗传学证据，据报道该染色体起源于13号或22号染色体。为了解决这个问题，通过与中期染色体原位杂交，分离出一个单拷贝DNA探针D22S9并将其定位到22q11。通过Southern印迹法和放射自显影片的光密度分析确定了CES患者中该序列的拷贝数。在有额外染色体的患者中发现有四个拷贝，而在一名22号染色体部分重复的患者中发现有三个拷贝。因此，该综合征是由22q11的DNA序列存在三个或四个拷贝所致；没有证据表明其他染色体的序列参与其中。这项工作证明了DNA序列剂量分析可如何用于研究不易用标准细胞遗传学分析的遗传疾病。
