Studies of human germinal mutations by deoxyribonucleic acid hybridization

Spontaneous mutations that occur in human germ cells contribute significantly to clinical disorders and result in premature mortality, incurable morbidity, mental handicap, and infertility. We have used molecular analysis of deoxyribonucleic acid to study the occurrence of spontaneous human germinal mutations. We examined 458 offspring and parents in 60 multigeneration human families. Probes for hypervariable loci were dispersed throughout all chromosomes to note the occurrence of new mutations. We found that both point mutations and insertion-deletion mutations occur frequently enough to be directly quantitated. The rates of occurrence detected at the molecular level are much greater than the rates detected with other modalities. The mutational rates at some loci approach 1% in live-born children. Such mutations appear to be sequence specific and related to the processes of meiosis or mitosis as they occur in the production of human gametes.