Yoshioka M, Vacek P M, Poseno T, Silver R, Finette B A
Department of Pediatrics, University of Vermont, Burlington, VT 05401, USA.
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):586-91. doi: 10.1073/pnas.96.2.586.
Limited information is available regarding the frequency, spectrum, and clinical relevance of somatic mutations in the developing fetus. The goal of this study was to determine somatic mutant frequencies (Mfs) at the hypoxanthine phosphoribosyltransferase (HPRT) reporter gene in cord blood T lymphocytes from preterm infants to gain insight into in utero mutational events. Mf determinations were made by using the HPRT T cell cloning assay on cord blood samples from 52 preterm infants. Natural logarithm Mfs (lnMfs) from preterm infants were compared with results from our database for full-term infants. Our analysis revealed higher lnMfs in cord blood T lymphocytes from preterm compared with full-term infants (P = 0.008). In addition, preterm females had significantly higher lnMfs compared with full-term females (P < 0.001), whereas preterm males were found to have significantly lower lnMfs than preterm females (P = 0.005). Regression analyses also demonstrate a significant relationship between lnMf and gestational age for preterm females that does not exist for preterm males. These results demonstrate the gender-specific association between Mf and age in humans.
关于发育中胎儿体细胞突变的频率、谱系及临床相关性的信息有限。本研究的目的是确定早产儿脐带血T淋巴细胞中次黄嘌呤磷酸核糖转移酶（HPRT）报告基因的体细胞突变频率（Mfs），以深入了解子宫内的突变事件。通过对52例早产儿的脐带血样本进行HPRT T细胞克隆分析来确定Mf。将早产儿的自然对数Mfs（lnMfs）与我们数据库中足月儿的结果进行比较。我们的分析显示，与足月儿相比，早产儿脐带血T淋巴细胞中的lnMfs更高（P = 0.008）。此外，早产女性的lnMfs显著高于足月女性（P < 0.001），而早产男性的lnMfs显著低于早产女性（P = 0.005）。回归分析还表明，早产女性的lnMf与胎龄之间存在显著关系，而早产男性不存在这种关系。这些结果证明了人类中Mf与年龄之间的性别特异性关联。
