ANNEX Hereditary effects of radiation

II. MENDELIAN DISEASES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 A. MOLECULAR NATURE OF MUTATIONS . . . . . . . . . . . . . . . . . . . . . . . . . 10 B. MUTATIONAL SPECIFICITIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 C. GENOTYPE-PHENOTYPE RELATIONSHIPS . . . . . . . . . . . . . . . . . . . . . . . 11 1. Mutations in the same gene causing different clinical phenotypes . . . . . . . 11 2. Mutations in different genes causing similar phenotypes . . . . . . . . . . . . . . 12 3. Identical mutations with different phenotypes . . . . . . . . . . . . . . . . . . . . . . 13 4. Mutations in the same genes inherited as both dominant and recessive . . . 13 5. Mosaicism, genomic imprinting, and uniparental disomy . . . . . . . . . . . . . . 14 6. Allelic expansion (dynamic mutations) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 7. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 D. BASELINE FREQUENCIES OF MENDELIAN DISEASES . . . . . . . . . . . . . 17 1. Autosomal dominant diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2. Autosomal recessive diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3. X-linked diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. Revision of the total birth frequency estimates . . . . . . . . . . . . . . . . . . . . . . 18 5. Population/ethnic differences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 6. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 E. SPONTANEOUS MUTATION RATES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 1. The concept of equilibrium between mutation and selection . . . . . . . . . . . 19 2. Spontaneous mutation rates for autosomal dominant and X-linked diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 3. Sex differences in mutation rates and paternal age effects . . . . . . . . . . . . . 20 4. Relevance of sex differences in spontaneous mutation rates and paternal age effects in humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 5. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22