Chromosome rearrangements have traditionally been detected by examination of the chromosomes with a microscope. Visual examination identifies chromosome rearrangements on the basis of changes in the overall size of a chromosome, alteration of banding patterns revealed by chromosome staining, or changes in the behavior of chromosomes in meiosis. Microscopy, however, can detect only large chromosome rearrangements, typically those that are at least 5 million base pairs in length.

With the completion of the Human Genome Project (see Chapter 15), detailed information about DNA sequences found on individual chromosomes became available. Using this information, geneticists can now examine the number of copies of specific DNA sequences present in a cell and detect duplications, deletions, and other chromosome rearrangements that cannot be observed with microscopy alone. This work has been greatly facilitated by the availability of microarrays (see Chapter 15), which allow the simultaneous detection of hundreds of thousands of specific DNA sequences from across the genome. Because these methods measure the number of copies of particular DNA sequences, the variations that they detect are called copy-number variations (CNVs). Copy-number variations include duplications and deletions that range in length from thousands of base pairs to several million base pairs. Many of these variants encompass at least one gene and may encompass several genes.

Recent studies of copy-number variations have revealed that submicroscopic chromosome duplications and deletions are quite common: research suggests that each person may possess as many as 1000 copy-number variations. Many probably have no observable phenotypic effects, but some copy-number variations have been implicated in a number of diseases and disorders. For example, Janine Wagenstaller and her colleagues studied copy-number variation in 67 children with unexplained intellectual disability and found that 11 (16%) of them had duplications or deletions. Copy-­number variations have also been associated with osteoporosis, autism, schizophrenia, and a number of other diseases and disorders. TRY PROBLEM 14