Jeffreys A J, Wilson V, Thein S L, Weatherall D J, Ponder B A
Am J Hum Genet. 1986 Jul;39(1):11-24.
Tandem-repetitive DNA hybridization probes based on a putative human recombination signal detect multiple polymorphic minisatellite fragments in human DNA. The genetic complexity of the resulting individual-specific DNA "fingerprints" was investigated by studying a large sibship affected by neurofibromatosis and a more extensive pedigree segregating for two different hemoglobinopathies. The segregation of up to 41 different heterozygous DNA fragments from each parent could be analyzed in a single sibship, using two different repeat probes. Most of these variable DNA fragments could not be paired as alleles, to an extent which suggests that the DNA fingerprints are together derived from approximately 60 heterozygous loci (approximately 120 variable fragments), only a proportion of which can be scored in a given individual. Two or three of the DNA fragments detected by one probe showed tight linkage and may be derived from long minisatellite(s) that are cleaved to produce more than one polymorphic DNA fragment. Excluding allelic and linked DNA fragments, almost all remaining scorable fragments segregated independently, allowing up to 34 unlinked loci to be examined simultaneously. These loci are scattered over most or all of the human autosomes. Minisatellite probes are therefore suitable for rapid marker generation and can be applied to linkage analysis in human pedigrees.
基于假定的人类重组信号的串联重复DNA杂交探针可检测人类DNA中的多个多态性小卫星片段。通过研究一个受神经纤维瘤病影响的大型同胞关系家族以及一个分离两种不同血红蛋白病的更广泛家系,对所得个体特异性DNA“指纹”的遗传复杂性进行了研究。使用两种不同的重复探针,在一个同胞关系家族中可以分析来自每个亲本的多达41个不同的杂合DNA片段的分离情况。这些可变DNA片段中的大多数不能作为等位基因配对,这表明DNA指纹共同来自大约60个杂合位点(大约120个可变片段),在给定个体中只能对其中一部分进行评分。由一种探针检测到的两三个DNA片段显示紧密连锁,可能来自被切割产生多个多态性DNA片段的长小卫星。排除等位基因和连锁DNA片段后,几乎所有其余可评分片段独立分离,可同时检测多达34个不连锁位点。这些位点分布在大多数或所有人类常染色体上。因此,小卫星探针适用于快速生成标记,并可应用于人类家系的连锁分析。