Fisher J H, Gusella J F, Scoggin C H
Proc Natl Acad Sci U S A. 1984 Jan;81(2):520-4. doi: 10.1073/pnas.81.2.520.
Identifying the specific DNA sequences involved in the chromosomal abnormalities in developmental and neoplastic diseases may be essential to understanding the molecular biology of these disorders. The use of recombinant DNA techniques in conjunction with rodent-human hybrid cells makes it possible to assign chromosomal locations to specific DNA sequences. However, the ubiquitous presence of reiterated DNA species often complicates the application of straightforward molecular hybridization. To accelerate the mapping of cloned sequences to specific chromosomal locations, we investigated the possibility that cloned sequences containing reiterated DNA might be used without isolating unique sequences. By varying conditions of hybridization (specifically temperature) and using restricted DNA samples from human genomic DNA, Chinese hamster ovary-human chromosome 11 hybrids, and non-chromosome 11 hybrids, we have been able to assign cloned DNA sequences containing reiterated sequences to their chromosome of origin. By hybridization under the high-stringency condition of 55 degrees C, specific banding was produced with both human genomic DNA and the human-chromosome-containing hybrid from which the probe was prepared. Furthermore, using a panel of chromosome 11 deletion mutants, we have been able to assign a cloned sequence to a specific chromosomal location. We believe that this approach will accelerate gene mapping procedures and facilitate identification of DNA sequences involved in chromosomal abnormalities.
识别发育性疾病和肿瘤性疾病中染色体异常所涉及的特定DNA序列,对于理解这些疾病的分子生物学可能至关重要。将重组DNA技术与啮齿动物-人类杂交细胞结合使用,使得将染色体位置分配给特定DNA序列成为可能。然而,重复DNA序列的普遍存在常常使直接分子杂交的应用变得复杂。为了加速将克隆序列定位到特定染色体位置,我们研究了含有重复DNA的克隆序列在不分离独特序列的情况下是否可用的可能性。通过改变杂交条件(特别是温度),并使用来自人类基因组DNA、中国仓鼠卵巢-人类11号染色体杂交细胞和非11号染色体杂交细胞的限制性DNA样本,我们已经能够将含有重复序列的克隆DNA序列定位到其起源染色体。在55摄氏度的高严格条件下进行杂交时,人类基因组DNA和制备探针所用的含人类染色体的杂交细胞都产生了特定的条带。此外,使用一组11号染色体缺失突变体,我们已经能够将一个克隆序列定位到特定的染色体位置。我们相信,这种方法将加速基因定位程序,并有助于识别与染色体异常有关的DNA序列。