Kojis T L, Schreck R R, Gatti R A, Sparkes R S
Medical Genetics-Birth Defects Center, Los Angeles, CA.
Hum Genet. 1989 Nov;83(4):347-52. doi: 10.1007/BF00291379.
Cytogenetic studies of lymphocytes and fibroblasts from individuals with ataxia-telangiectasia (AT) demonstrate spontaneous chromosomal breakage. In the AT lymphocytes, this damage results in a high frequency of balanced rearrangements involving chromosome bands 7p14, 7q35, 14q12, and 14q32. The T-cell receptor alpha, beta, and gamma chain gene complexes and the immunoglobulin heavy chain gene complex, all of which may be functional in lymphocytes, have been localized to these bands. To assess the relationship between genes at these breakpoints and the entirety of the AT phenotype, we undertook a detailed cytogenetic analysis of fibroblasts and lymphocytes from seven AT homozygotes. Our findings indicate that the rearrangements present in the lymphocytes are not commonly observed in the fibroblasts, despite the increased instability of chromosomes from the cells relative to lymphocytes. Furthermore, the changes in the fibroblasts are neither consistent within nor between patients, suggesting that chromosome rearrangement occurs more randomly in this tissue. Therefore, differential site-specific damage in separate tissue may generate the distinct features of the disease in those tissues and may account for the pleiotrophic effects of the AT gene.
对共济失调毛细血管扩张症（AT）患者的淋巴细胞和成纤维细胞进行的细胞遗传学研究表明存在自发染色体断裂。在AT淋巴细胞中，这种损伤导致涉及染色体带7p14、7q35、14q12和14q32的平衡重排频率很高。T细胞受体α、β和γ链基因复合体以及免疫球蛋白重链基因复合体，所有这些在淋巴细胞中可能具有功能，都已定位到这些染色体带。为了评估这些断点处的基因与整个AT表型之间的关系，我们对7名AT纯合子的成纤维细胞和淋巴细胞进行了详细的细胞遗传学分析。我们的研究结果表明，尽管相对于淋巴细胞，这些细胞的染色体不稳定性增加，但淋巴细胞中存在的重排在成纤维细胞中并不常见。此外，成纤维细胞中的变化在患者内部和患者之间都不一致，这表明染色体重排在该组织中发生得更为随机。因此，不同组织中不同位点特异性损伤可能在这些组织中产生疾病的不同特征，并可能解释AT基因的多效性效应。
