Change in the structure or sequence of a gene is called a mutation. A mutation can occur randomly anywhere along the DNA sequence of a gene and may result when one nucleotide is substituted for another (point mutation). A mutation that occurs in a noncoding portion of the gene may or may not be of clinical consequence. Similarly, a mutation may structurally alter a protein but in a manner that does not notably compromise its function. A new mutation that compromises function may appear in a given gene as the gene is transmitted from parent to offspring.
More gross mutations may involve deletion, translocation, insertion, or internal duplication of a portion of the DNA. Some mutations cause either destruction of the offspring or sterility. Others are less harmful or are potentially beneficial and become established in subsequent generations. Mutations can occur spontaneously for reasons that are not understood. They may also be induced by exposure to a variety of environmental agents called mutagens, such as radiation, viruses, and certain chemicals.
Mutations may arise in somatic as well as germinal cells, but these are not transmitted to subsequent generations. Somatic mutations in humans are difficult to identify, although some account for the inception of certain forms of neoplasia (eg, retinoblastoma).
Many base changes have little or no deleterious effect on the organism. A polymorphism is defined as the occurrence of 2 or more alleles at a specific locus with a frequency greater than 1% each in a given population. Single nucleotide polymorphisms (SNPs) are important for gene mapping in genome-wide association studies (GWAS).
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.