Segregation Analysis of Autosomal Dominant Polycystic Kidney Disease
A. Dobin, W.J. Kimberling, W. Pettinger, J.E. Bailey-Wilson,
Y.Y. Shugart, P. Gabow
Genetic Epidemiology , 10(3), 189--200 (1993)
Abstract
The results of classical segregation analysis on 159 families with
polycystic kidney disease (PKD) are presented. It had been
previously estimated that about 95% of autosomal dominant PKD
(ADPKD) families have PKD1, the gene localized to chromosome 16p.
The main purpose of the study was to determine if PKD shows any
segregation distortion and to obtain new estimates of the
age-dependent penetrance. Penetrance at the early ages of onset has
increased during the last decade, presumably because of improvements
in renal imaging and consequent earlier age of diagnosis. In the
current study, the mean age of diagnosis was estimated to be 20
years, with a standard deviation (SD) of 15.94. Under the best
fitting model (autosomal dominant), over 70% penetrance was
estimated by age 30 years, over 95% by 50 years, and 99% by 55
years. Thus, diagnosis of this disease at an early age is possible
without total reliance on DNA typing. The segregation ratio defined
through the transmission probability in our model was not
significantly different from 0.50, but its confidence limits were
broad: 0.36 to 0.64. Neither transmission probability nor penetrance
was significantly influenced by gender. The mutation rate was
estimated to be 6.9 x 10(-5), in accordance with the previously
observed high mutation rate for PKD. However, the mutation rate in
our study may be overestimated because it neglects low penetrance
alleles and phenocopies.
