Chromosomal Instability in Lymphoblastoid Cell Lines Derived from Patients with Different Inherited disorders

不同遗传性疾病患者来源的淋巴母细胞系的染色体不稳定性

基本信息

批准号：
61571089
负责人：
IKEUCHI Tatsuro
金额：
$ 1.41万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Permanent growing lymphoblastoid cell lines (LCL) established by EB virus-mediated transformation of lymphocytes are now of great practial value in both clinical and experimental human genetics. We have established a series of LCL from patitents or families with various hereditary diseases. In order to confirm their availability and to obtain the basic guidelines for the maintenance of LCL, we have examined cytogenetic characters of these LCL in the course of prolonged culture condition. The results are as follows:1) The LCL established for the last 2 years include: 87 lines from 36 families with familial polyposis coli (FPC), 24 lines from 6 families with multiple endocrine neoplasia type 2 (MEN2), 19 lines from heritable fragile site (FS) carriers, and 14 lines from patients with various chromosomal abnormalities.2) Karyotype analyses were made on prolonged cultures (2 months to 1.5 year) of LCL from MEN2 families and from FS carriers. In general,acquired chromosome abnormalities app … More eared four months after the establishment, regardless of their genetic sources (age, ses, carriers or noncarriers). In some of the LCL maintained in vitro for more than one year, almost all of the cells showed abnormal karyotypes with clonal chromosome changes. The abnormalities were mostly of numerical type with a predominance of trisomies of Nos. 5, 8, 12 and 15 chromosomes.3) Expression rates of FS in LCL derived from heritable FS carriers were in general very low (<3%), but a cell line "B-3",derived froma RdU-required fra(10)(q25) carrier, expressed the FS with high frequencies (40-60%) after exposure to 5-bromodeoxyuridine (7<micrn>g/ml) for 24 hours. 4) In LCL from patients with a ring chromosome, r(18) and r(21), respectively, the rings were retained even after prolonged culture for 4 months. This indicates the morphological stability of the rings in which the small-sized chromosomes were involved.5) Some of the LCL here establsihed were efficiently employed for regional mapping of cloned DNA segments (D13S21), D13S22 and D18S5). The LCL from MEN2 and FPC families could be applied to the linkage analysis and to the esarch inn tumors for somatic loss of constitutinal heterozygosity.6) In experiments using the cell line "B-3", it was found that the fra(10)(p25) expression distribution of thymine between the two strands of DNA duplex in the fra(10) site. Less

永久生长的淋巴细胞细胞系（LCL）EB病毒介导的淋巴细胞转化是临床和实验性人类遗传学的转化。维持长期培养条件的LCL E。 2（MEN2）易碎部位（FS）携带者和来自各种染色体异常的患者的14条线。2）核型分析是对长期培养物（2个月至1.5年）的LCLN MEN2家族和FS携带者的…在建立的四个月后，无论其遗传来源如何。 MA RDU率的FRA（10）Q25）载体在暴露于5-溴脱氧尿苷（7 <micrn> g/ml）24小时后，以高频（40-60％）表示FS。（18）和r（21），在延长培养物4个月后保留了伊甸园。，D13S22和D18S5）。（10）（p25）矿山在FRA（10）位置的两个双链体之间的表达分布。