Nakamura Y, Leppert M, O'Connell P, Wolff R, Holm T, Culver M, Martin C, Fujimoto E, Hoff M, Kumlin E
Science. 1987 Mar 27;235(4796):1616-22. doi: 10.1126/science.3029872.
A large collection of good genetic markers is needed to map the genes that cause human genetic diseases. Although nearly 400 polymorphic DNA markers for human chromosomes have been described, the majority have only two alleles and are thus uninformative for analysis of genetic linkage in many families. A few known marker systems, however, detect loci that respond to restriction enzyme cleavage by producing a fragment that can have many different lengths. This polymorphism is due to variation in the number of tandem repeats of a short DNA sequence. Because most individuals will be heterozygous at such loci, these markers will provide linkage information in almost all families. Ten oligomeric sequences derived from the tandem repeat regions of the myoglobin gene, the zeta-globin pseudogene, the insulin gene, and the X-gene region of hepatitis B virus, were used to develop a series of single-copy probes. These probes revealed new, highly polymorphic genetic loci whose allele sizes reflected variation in the number of tandem repeats.
要绘制导致人类遗传疾病的基因图谱，需要大量优质的遗传标记。尽管已经描述了近400个人类染色体的多态性DNA标记，但大多数只有两个等位基因，因此在许多家族的遗传连锁分析中缺乏信息。然而，一些已知的标记系统可检测到能对限制酶切割产生反应的位点，产生具有许多不同长度的片段。这种多态性是由于短DNA序列串联重复次数的变化所致。由于大多数个体在这些位点是杂合的，这些标记几乎能为所有家族提供连锁信息。从肌红蛋白基因、ζ-珠蛋白假基因、胰岛素基因和乙肝病毒X基因区域的串联重复区域衍生出的10个寡聚序列，被用于开发一系列单拷贝探针。这些探针揭示了新的、高度多态的遗传位点，其等位基因大小反映了串联重复次数的变化。
