A simple method for calculating risks before DNA analysis.
Calculation of carrier risk of an X linked disease may be performed on a small computer after DNA analysis, but a method for rapid hand estimation of the risk is still useful for a quick check of the results and weighing the relative importance of each element of information, such as the determination of a haplotype. Each risk estimation is a function of a prior risk and the product of likelihood ratios and these terms are derived themselves from parameters such as fitness or the relative mutation rate in male and female gametes. Even if it is often difficult to have strong experimental estimation of these variables, the existence of a normal father or grandfather must be considered whenever male fitness is not null. The likelihood ratio for a woman for not being a carrier, when her father is not affected and her mother has herself a likelihood R for not having the mutated gene, may be expressed as the ratio 2R/(CmR + 1), with Cm being a function of male fitness and relative mutation rate. Cm represents the odds ratio for the mother of a carrier not to be a carrier, given that the father of the known carrier is not affected. This formula can be used recurrently and reduces to 2R/(R + 1) in lethal X linked disease. When likelihood ratios are expressed as an algebraic function, maximum values are easily determined, hence fixing the limits of DNA analysis.
Jeanpierre
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Service de Biochimie Génétique et Unité INSERM U129, CHU Cochin, Paris, France.
D004247:DNA / Q000235:genetics; D005260:Female; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D010375:Pedigree; D011336:Probability; D012307:Risk Factors; D014960:X Chromosome
D004247:DNA