Nancarrow J K, Kremer E, Holman K, Eyre H, Doggett N A, Le Paslier D, Callen D F, Sutherland G R, Richards R I
Department of Cytogenetics and Molecular Genetics, Women's and Children's Hospital, North Adelaide, South Australia.
Science. 1994 Jun 24;264(5167):1938-41. doi: 10.1126/science.8009225.
Fragile sites are chemically induced nonstaining gaps in chromosomes. Different fragile sites vary in frequency in the population and in the chemistry of their induction. DNA sequences encompassing and including the rare, autosomal, folate-sensitive fragile site, FRA16A, were isolated by positional cloning. The molecular basis of FRA16A was found to be expansion of a normally polymorphic p(CCG)n repeat. This repeat was adjacent to a CpG island that was methylated in fragile site-expressing individuals. The FRA16A locus in individuals who do not express the fragile site is not a site of DNA methylation (imprinting), which suggests that the methylation associated with fragile sites may be a consequence and not a cause of their genesis.
脆性位点是化学诱导产生的染色体上的不着色间隙。不同的脆性位点在人群中的出现频率以及诱导它们的化学物质方面存在差异。通过定位克隆分离出了包含罕见的常染色体叶酸敏感脆性位点FRA16A及其周边的DNA序列。结果发现，FRA16A的分子基础是一个正常多态性的p(CCG)n重复序列的扩增。该重复序列毗邻一个在表达脆性位点的个体中发生甲基化的CpG岛。在不表达脆性位点的个体中，FRA16A位点并非DNA甲基化（印记）位点，这表明与脆性位点相关的甲基化可能是其产生的结果而非原因。
