Kato M V, Ishizaki K, Shimizu T, Ejima Y, Tanooka H, Takayama J, Kaneko A, Toguchida J, Sasaki M S
Radiation Biology Center, Kyoto University, Japan.
Hum Genet. 1994 Jul;94(1):31-8. doi: 10.1007/BF02272838.
Segregation analysis of polymorphic sites within the retinoblastoma (RB) gene and on chromosome 13, as well as the parental origin of the lost allele in the tumor, were analyzed in 24 families with RB patients. Four mutant alleles transmitted through the germ-line and seven de novo germ-line mutant alleles were identified in 11 patients with hereditary RB. Segregation analysis within the RB gene and on chromosome 13 was useful for DNA diagnosis of susceptibility to RB in relatives of hereditary patients, even if mutations were not identified. All seven de novo germ-line mutant alleles were paternally derived. The bias toward the paternal allele for de novo germ-line mutations of the RB gene was statistically significant. Seven paternal alleles and six maternal alleles were lost in 13 non-hereditary RB tumors with no bias in the parental origin of the somatic allele loss. These results suggest that the physical environment or a deficiency in DNA repair during spermatogenesis may be associated with significant risk factors for de novo germ-line mutations.
在24个患有视网膜母细胞瘤（RB）患者的家庭中，对RB基因内和13号染色体上的多态性位点进行了分离分析，以及肿瘤中缺失等位基因的亲本来源。在11例遗传性RB患者中鉴定出4个通过种系传递的突变等位基因和7个新生种系突变等位基因。即使未鉴定出突变，RB基因内和13号染色体上的分离分析对于遗传性患者亲属中RB易感性的DNA诊断也很有用。所有7个新生种系突变等位基因均来自父系。RB基因新生种系突变偏向父系等位基因具有统计学意义。在13例非遗传性RB肿瘤中，7个父系等位基因和6个母系等位基因丢失，体细胞等位基因丢失的亲本来源无偏向性。这些结果表明，精子发生过程中的物理环境或DNA修复缺陷可能与新生种系突变的重要风险因素有关。
