Medical Genetics - V. M. Zaporozhan 2005

Etiology of Hereditary Diseases
Gene Mutations
Frequency of Gene Mutations

De novo Mutations create a mutational load within a population. If these mutations do not affect an individual's viability or fertility, they can be passed down from generation to generation according to Mendel's Laws. The genetic load caused by them is known as the segregation load. Certain recessive genes may confer a selective advantage to their carriers in the heterozygous state, which facilitates the accumulation of such genes in the population. For instance, the Sickle-Cell Anemia Gene is prevalent in Mediterranean countries because heterozygotes for this gene are resistant to malaria. Similarly, heterozygotes for the cystic fibrosis gene may have had a higher resistance to cholera, allowing this gene to accumulate in southern Ukraine.

Dominant mutations that impair fertility or are lethal cannot be inherited at all; rather, they arise anew in each generation.

The average mutation rate for various genes ranges from 10^-5 to 10^-6 per gamete per generation (i.e., from 1 mutation per 10⁵ Gametes to 1 per 10⁶ gametes). However, this value can vary from 10^-4 for highly mutable genes to 10^-11 for the most stable ones. Examples of mutation frequencies for certain disease-causing genes are presented in Table 2.2.

As shown in the table, the mutation rate of a single gene is low. Nevertheless, The Human Genome contains a vast number of genes (approximately 30,000). Assuming an average mutation rate of 10^-5, the average number of gene mutations can be estimated as follows: (30х10³ genes) x (10^-5 mutations per gene) = 30 mutations per 100 gametes, or 1 mutation per 3 gametes.

Table 2.2. Mutation frequencies of certain human genes (after F. Vogel and A. Motulsky)

Note. AD — Autosomal dominant inheritance; XR — X-linked recessive.

New mutations represent a vital source of genetic variation, which serves as the foundation for biological evolution.