Bisgaard M L, Fenger K, Bülow S, Niebuhr E, Mohr J
Department of Medical Biochemistry and Genetics, University of Copenhagen, Denmark.
Hum Mutat. 1994;3(2):121-5. doi: 10.1002/humu.1380030206.
The nationwide Danish polyposis register includes all known Danish cases of familial adenomatous polyposis (FAP) and their relatives. By identifying all FAP patients born between 1920 and 1949, we found the frequency of the disease to be 1 in 13,528. By comparing the number of affected and nonaffected offspring born to affected parents during the same period we found the penetrance of the disease for inherited cases to be close to 100% at the age of 40 years. The mutation rate found by the direct method was 9 mutations per million gametes per generation and the proportion of new mutants was estimated to 25%. Fitness for patients between 15 and 29 years was found close to one, while for patients older than 30 the fitness was reduced, but increasing during the three decades (from 0.44 to 0.71) probably because treatment became more widespread and efficient. As we have used the overall fitness in the period, 0.87, to estimate the mutation rate by the indirect method, we found a lower value than by the direct method, namely 5 mutations per million gametes per generation.
丹麦全国性息肉病登记册涵盖了丹麦所有已知的家族性腺瘤性息肉病（FAP）病例及其亲属。通过识别1920年至1949年出生的所有FAP患者，我们发现该病的发病率为1/13528。通过比较同期患病父母所生的患病和未患病后代数量，我们发现遗传病例在40岁时的疾病外显率接近100%。直接法得出的突变率为每代每百万配子9次突变，新突变体的比例估计为25%。15至29岁患者的适合度接近1，而30岁以上患者的适合度降低，但在三十年期间有所增加（从0.44增至0.71），这可能是因为治疗变得更加普及和有效。由于我们使用该时期的总体适合度0.87通过间接法估计突变率，我们得到了一个比直接法更低的值，即每代每百万配子5次突变。
