How many deleterious mutations are there in the human genome?

An estimate of the number of deleterious mutations in the human genome is m ade using data on the frequency of rare recessive disease in cousin marriag es and in the general population. Sexual reproduction ensures that deleteri ous mutations are distributed at random in zygotes with an approximate Pois son distribution. The mean of this distribution is the sum of the mean numb er of deleterious mutations in zygotes which contribute to the next generat ion (Y) and the mean number of new mutations which arise in each human gene ration (X). The estimates are that X is between 1 and 2.6 and Y is between 12 and 32. A mathematical model based on redundancy is then used to predict how zygote survival will vary with the number of deleterious mutations. Th e form of this relationship is the same as that seen in experiments on cell survival following radiation-induced mutational damage and this provides i ndependent support for this theoretical approach. The zygotes that survive to contribute to the next generation have a skewed distribution with a mean of Y. It is argued that the number of deleterious mutations in the genome is an important variable in health and disease. (C) 2001 Harcourt Publisher s Ltd.