Genetic Predisposition to Cancer by D. Timothy Bishop (auth.), Rosalind A. Eeles, Bruce A. J.

By D. Timothy Bishop (auth.), Rosalind A. Eeles, Bruce A. J. Ponder, Douglas F. Easton, Alan Horwich (eds.)

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Easton, D. and Peto, J. (1990) The contribution of inherited predisposition to cancer incidence. , 9(3), 395-416. 20. J. D. (1990) Age at onset as an indicator of familial risk of breast cancer. Am. J. , 131, 961-72. 21. , Risch, N. D. (1991) Genetic analysis of breast cancer in the Cancer and Steroid Hormone study. Am. J. Hum. , 48(2), 232-42. 14 22. A. (1961) Blood groups and disease, in Progress in Medical Genetics, (ed. G. Steinberg), Vol. 1, Grune and Stratton, New York, pp. 81-119. 23. , White, K, Skolnick, M.

The optimal linkage designs for detecting relatively common low penetrance genes are not as clear as for rare high penetrance genes. 3, families with three or four cases are almost always more powerful than affected pairs. However, families with large numbers of affected indiv(auals may be less efficient in this case for two reasons. First, because the disease gene is common; families with many affected members could be segregating more than one copy of the disease susceptibility allele. This could make the family uninformative for linkage if the transmitting parent were homozygous at the disease locus.

However, the genetic distance is not related linearly to physical distance, since there are known regions of high and low recombination per unit physical distance. In particular, centromeres are known to be regions of low recombination, whereas the telomereric regions tend to exhibit high recombination rates. The rate of recombination differs 18 between male and female meioses; overall the female recombination rate is higher but the pattern across each chromosome differs between the sexes and there are regions where the male recombination rate is higher.

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