Whereas most mutations involve only one or a few nucleotides, some affect larger regions extending over hundreds of thousands or millions of nucleotides and have effects on chromosome structure that are often large enough to be visible through an ordinary optical microscope. Double-stranded breaks in DNA that are incorrectly repaired can lead to chromosomal mutations. The breaks may result from interactions between DNA and reactive molecules produced in metabolism or from reactive chemicals in the environment or by radiation (especially X-rays). Chromosomal mutations can also arise from errors in DNA replication, particularly in sequences that are tandemly repeated along the DNA (Chapter 13).

Chromosomal mutations can delete or duplicate regions of a chromosome containing several or many genes, and the resulting change in gene copy number also changes the amount of the products of these genes in the cell. Chromosomal mutations can also alter the linear order of genes along a chromosome or interchange the arms of nonhomologous chromosomes. While these types of chromosomal mutations do not change gene copy number, they do affect chromosome pairing and segregation in meiosis. These effects distinguish chromosome abnormalities from nucleotide substitutions, small-scale deletions and duplications, transpositions, and other submicroscopic mutations. In this section, we briefly consider the major types of chromosome abnormalities in more detail.