Deletions

A second type of chromosome rearrangement is a deletion, the loss of a chromosome segment (see Figure 9.5b). A chromosome with segments AB^CDEFG that undergoes a deletion of segment EF would generate the mutated chromosome AB^CDG.

A large deletion can be easily detected because the chromosome is noticeably shortened. In individuals heterozygous for deletions, the normal chromosome must loop out during the pairing of homologs in prophase I of meiosis (FIGURE 9.10) to allow the homologous regions of the two chromosomes to align and undergo synapsis. This looping out generates a structure that looks very much like that seen in individuals heterozygous for duplications.

The phenotypic consequences of a deletion depend on which genes are located in the deleted region. If the deletion includes the centromere, the chromosome will not segregate in meiosis or mitosis and will usually be lost. Many deletions are lethal in the homozygous state because all copies of any essential genes located in the deleted region are missing. Even individuals heterozygous for a deletion may have multiple defects for three reasons.

First, the heterozygous condition may produce imbalances in the amounts of gene products, similar to the imbalances produced by extra gene copies. Second, deletions may allow recessive mutations on the undeleted chromosome to be expressed (because there is no wild-type allele to mask their expression). This phenomenon is referred to as pseu-dodominance. The appearance of pseudodominance in otherwise recessive alleles is an indication that a deletion is present on one of the chromosomes. Third, some genes must be present in two copies for normal function. Such a gene is said to be haploinsufficient; loss of function mutations in haploinsufficient genes are dominant. Notch is a series of X-linked wing mutations in Drosophila that often result from chromosome deletions. Notch deletions behave as dominant mutations: when heterozygous for the Notch deletion, a fly has wings that are notched at the tips and along the edges ( FIGURE 9.11). The Notch locus is therefore haploinsufficient—a single copy of the gene is not sufficient to produce a wild-type phenotype. Females that are homozygous for a Notch deletion (or males that are hemizy-gous) die early in embryonic development. The Notch gene codes for a receptor that normally transmits signals received from outside the cell to the cell's interior and is important in fly development. The deletion acts as a recessive lethal because loss of all copies of the Notch gene prevents normal development.

In humans, a deletion on the short arm of chromosome 5 is responsible for cri-du-chat syndrome. The name

Wild-type chromosome

Gene expression

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