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Copy number variation is variation in the number of copies of a particular DNA segment among genomes. A deletion reduces the count; a duplication increases it. For an segment on a non-sex chromosome normally present once on each of two homologous chromosomes, a diploid cell usually has two copies, whereas one additional tandem copy produces a total of three.

The number must be interpreted against a specified baseline. In an ideal comparison with equal sample normalization, three copies versus two give a DNA abundance ratio of $3/2$, or ${\log }_2(3/2)\approx 0.585$ on a logarithmic readout. This arithmetic does not imply that gene expression must rise by the same proportion.

Genome-wide DNA hybridization experiments in 2004 found substantial large-scale copy number variation among otherwise healthy individuals. Such variation is part of ordinary human genetic diversity as well as a possible contributor to disease.^[ref]

Gene copy number is the count of copies of a specified gene sequence relative to a stated reference, such as one genome or one biological cell. The reference matters: the count per cell can change with the number of genome equivalents even when the count per genome is unchanged. A DNA copy count also differs from gene expression or the amount of its protein product.

A primary example is the 16S ribosomal RNA gene. A2004 study compared gene copies and their sequence differences within bacterial and archaeal genomes. It showed why a marker's copy count and sequence diversity must be considered separately when interpreting community data.^[ref]

For an invented ideal assay,200 cells of population A carry two target copies each, while100 cells of population B carry four each. Both supply400 templates, giving equal template shares despite cell shares of $2/3$ and $1/3$. More generally, a response can scale as $N_i{k}_i{e}_i$, where $N_i$ is cell count, $k_i$ copies per cell and $e_i$ combined recovery/amplification efficiency. Inferring cell numbers then requires information about the other factors. Copy number variation describes a biological source of changing counts; an assay response alone does not establish which source caused a difference.

Genomic copy number is the count of copies of a specified DNA sequence in a defined biological unit, such as a cell or a haploid-equivalent genome. The sequence and denominator matter: a two-copy autosomal locus in a diploid cell is one copy per haploid genome, while a deletion or duplication can alter that locus without changing the ploidy of the whole cell. Such segment-level differences underlie copy number variation.^[ref]

DNA replication also changes the number of DNA molecules during the cell cycle. A replicated chromosome contains sister copies without thereby becoming two independently counted chromosomes under the usual centromere-based convention. Report the cell-cycle stage when comparing absolute DNA copies per cell.

Sequencing depth can estimate relative genomic copy number by comparing coverage with a reference region, but library preparation, sequence-dependent mapping and population mixtures affect that comparison. In a hypothetical mixture where half the cells carry two copies and half carry four, the mean is three copies per cell; that average does not show that any individual cell carries three. Genomic copy number also differs from the number of expressed RNA or protein molecules. This distinction matters when connecting gene dosage to a molecular abundance model.

Jonathan Sebat led a 2004 study demonstrating widespread large-scale copy number variation in the human genome. Comparing genomic DNA by hybridization detected regions whose copy numbers differed among individuals; many differences were inherited.^[ref]

A person can therefore differ from another not only at individual nucleotides, but also in how many copies of a substantial DNA segment are present. Comparing signal intensities supplied evidence for dosage differences that sequence substitutions alone would miss. The result helped make structural variation a routine part of questions about human genetic diversity.