Chaganti R S, Schonberg S, German J
Proc Natl Acad Sci U S A. 1974 Nov;71(11):4508-12. doi: 10.1073/pnas.71.11.4508.
Dividing cells from persons with Bloom's syndrome, an autosomal recessive disorder of growth, exhibit increased numbers of chromatid breaks and rearrangements. A highly characteristic feature of the chromosome instability in this syndrome is the tendency for exchanges to occur between chromatids of homologous chromosomes at homologous sites. In the present experiments, a cytogenetic technique by which the sister chromatids of a metaphase chromosome are stained differentially has been used to demonstrate a striking and possibly specific, but hitherto unrecognized, increase in the frequency with which sister chromatids also exchange segments. The cells were grown in bromodeoxyuridine and stained with 33258 Hoechst and Giemsa. Whereas phytohemagglutinin-stimulated lymphocytes from normal controls had a mean of 6.9 sister chromatid exchanges per metaphase (range 1-14), those from persons with Bloom's syndrome had a mean of 89.0 (range 45-162). Normal frequencies of sister chromatid exchanges were found in cells heterozygous for the Bloom's syndrome gene, and also in cells either homozygous or heterozygous for the genes of the Louis-Bar (ataxia telangiectasia) syndrome and Fanconi's anemia, two other rare disorders characterized by chromosome instability. In a differentially stained chromatid interchange configuration discovered during the study, it was possible to determine the new distribution of both sister and non-sister-but-homologous chromatids that had resulted from numerous exchanges. By following shifts in the pattern of staining from chromatid to chromatid, visual evidence was obtained that the quadriradial configurations long recognized as characteristic of Bloom's syndrome represent exchanges between homologous chromosomes, apparently at homologous points. We postulate that the increase in the frequency of exchanges between nonsister-but-homologous chromatids and those between sister chromatids in Bloom's syndrome represents aspects of one and the same disturbance. A study of this phenomenon in relation to the clinical features of Bloom's syndrome may be helpful eventually in understanding the biological significance of chromatid exchange in somatic cells.
患有布卢姆综合征（一种常染色体隐性生长障碍疾病）的人的分裂细胞显示出染色单体断裂和重排的数量增加。该综合征中染色体不稳定性的一个高度特征性表现是同源染色体的染色单体在同源位点之间发生交换的倾向。在本实验中，一种使中期染色体的姐妹染色单体产生差异染色的细胞遗传学技术被用于证明姐妹染色单体之间交换片段的频率显著增加，这一现象可能具有特异性，但迄今尚未被认识到。细胞在溴脱氧尿苷中培养，并用33258 Hoechst和吉姆萨染色。正常对照的植物血凝素刺激淋巴细胞每个中期的姐妹染色单体交换平均为6.9次（范围为1 - 14次），而患有布卢姆综合征的人的淋巴细胞平均为89.0次（范围为45 - 162次）。在布卢姆综合征基因杂合的细胞中，以及在另外两种以染色体不稳定性为特征的罕见疾病——路易斯 - 巴尔（共济失调毛细血管扩张症）综合征和范科尼贫血症的基因纯合或杂合的细胞中，均发现了正常频率的姐妹染色单体交换。在研究过程中发现的一种差异染色的染色单体互换构型中，有可能确定由于大量交换而导致的姐妹染色单体和非姐妹但同源染色单体的新分布。通过追踪染色单体之间染色模式的变化，获得了视觉证据，即长期以来被认为是布卢姆综合征特征的四射体构型代表同源染色体之间的交换，显然是在同源点处。我们推测，布卢姆综合征中非姐妹但同源染色单体之间以及姐妹染色单体之间交换频率的增加代表了同一干扰的不同方面。对这一现象与布卢姆综合征临床特征相关的研究最终可能有助于理解体细胞中染色单体交换的生物学意义。
