German J, Ellis N A, Proytcheva M
Laboratory of Human Genetics, New York Blood Center, New York 10021, USA.
Clin Genet. 1996 May;49(5):223-31. doi: 10.1111/j.1399-0004.1996.tb03778.x.
Cells with abnormally high rates of sister-chromatid exchange (SCE) are uniquely characteristic of Bloom's syndrome (BS). However, in one in five persons a minor population of cells with a low-SCE phenotype circulates in the blood. The origin and significance of the low-SCE cells in BS have never been understood, although they are assumed to arise by somatic mutation. In the present investigation, the enigmatic high-SCE/low-SCE mosaicism was investigated by comparing the incidence in several subpopulations of persons in the Bloom's Syndrome Registry who exhibit the two types of cells, and a striking negative correlation emerged: in persons with BS whose parents share a common ancestor, the case in approximately half of registered persons, low-SCE cells are found only rarely; conversely, the mosaicism occurs almost exclusively in persons with BS whose parents are not known to share a common ancestor. Because those who share a common ancestor are predominantly homozygous-by-descent at the mutated BS locus, the negative correlation is interpreted to mean that the emergence of low-SCE cells in BS in some way depends on the pre-existence of compound heterozygosity. A corollary to this is that BS is genetically heterogeneous.
姐妹染色单体交换（SCE）率异常高的细胞是布卢姆综合征（BS）的独特特征。然而，每五个人中就有一个人的血液中循环着一小部分具有低SCE表型的细胞。尽管人们认为BS中低SCE细胞是由体细胞突变产生的，但其起源和意义一直未被理解。在本研究中，通过比较布卢姆综合征登记处中表现出这两种细胞类型的几个亚人群中的发生率，对神秘的高SCE/低SCE嵌合体进行了研究，结果出现了显著的负相关：在父母有共同祖先的BS患者中（约占登记患者的一半），低SCE细胞很少被发现；相反，这种嵌合体几乎只出现在父母没有共同祖先的BS患者中。由于有共同祖先的人在突变的BS位点主要是同源纯合子，因此这种负相关被解释为意味着BS中低SCE细胞的出现以某种方式依赖于复合杂合性的预先存在。由此得出的一个推论是，BS在遗传上是异质性的。
