CARRIER RISK CALCULATIONS FOR RECESSIVE DISEASES WHEN NOT ALL THE MUTANT ALLELES ARE DETECTABLE

The number of recessive diseases, such as cystic fibrosis, in which so me but not all of the mutations causing the disease can be detected us ing genetic probes, is certain to in crease. For counselling purposes, the probability that a consultand known not to have a detectable muta tion is nevertheless a carrier, needs to be calculated with as much ac curacy as possible. This paper describes a program, available from the author, written specifically to make these calculations. As an exampl e, results are presented for cystic fibrosis, assuming an incidence of 1 in 2,400 and that 80% of the mutations, being Delta F508 mutations, are detectable. Numerical results are given when information may be a vailable on the parents, one or two sibs and one or two children of th e consultand. When test results are available on the children, the tes t status of the spouse of the consultand is relevant and may also be a vailable. Risk calculations are also presented when an aunt (uncle) of the consultand has cystic fibrosis. Finally, disease and carrier risk s are given for the child of first cousins, neither of whom has a dete ctable mutation. (C) 1994 Wiley-Liss, Inc.