Major impacts of gonadal mosaicism on hereditary risk estimation, origin of hereditary diseases, and evolution
Major impacts of gonadal mosaicism on hereditary risk estimation, origin of hereditary diseases, and evolution
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DOI：
10.1023/a:1017018705590
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发表时间：
1998-01-01
期刊：
影响因子：
1.5
通讯作者：
Selby, PB
中科院分区：
文献类型：
--
作者：
Selby, PB
在小鼠中的特定位点测试是迄今为止最广泛应用的精确确定哺乳动物基因突变频率的方法。基于大量历史数据，对涉及5740万后代的对照实验进行了计算机模拟，结果表明，由于性腺镶嵌现象，每一代自发突变的总频率比人们想象的要高得多。在特定位点实验中检测的7个基因的估计两性组合自发突变频率为39.6 x 10（-5）突变/配子。将这一频率除以两性父母的综合诱发突变频率，得出加倍剂量（DD）估计值为5.4 - 7.7戈伊。几十年来，DD一直被认为是约1戈伊。随着DD的增加，基于它的遗传风险估计会减少。因此，这一新认识的一个重要后果是，通常采用加倍剂量方法对辐射对人类的遗传风险进行的估计可能至少高出五倍。同时，性腺镶嵌现象在进化和遗传性疾病的起源中所起的作用似乎比过去所认识的要重要得多。
The specific-locus test in mice is by far the most extensively applied method for precisely defining gene mutation frequencies in mammals. Computer simulations of control experiments involving 57.4 million offspring, based on vast amounts of historical data, show that because of gonadal mosaicism, the total frequency of spontaneous mutations per generation is much higher than has been thought. The estimated combined spontaneous mutation frequency for both sexes for the seven genes tested in specific-locus experiments is 39.6 x 10(-5) mutation/gamete. Division of this frequency by the combined induced mutation frequencies in parents of both sexes results in an estimate of the doubling-dose (DD) of from 5.4 to 7.7 Gy. For decades, the DD has been thought to be about 1 Gy. As the DD increases, estimates of hereditary risk that are based upon it decrease. Thus, one important ramification of this new understanding is that estimates of the hereditary risk to humans from radiation, commonly made by the doubling-dose (DD) approach, are probably at least five times too high. It also appears that gonadal mosaicism is likely to play a much more important role both in evolution and the origin of hereditary diseases than has been appreciated in the past.