A second type of chromosome rearrangement is a chromosome deletion, the loss of a chromosome segment (see Figure 6.4b). 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 6.9) 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.

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EFFECTS OF DELETIONS 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, normally recessive mutations on the homologous chromosome lacking the deletion may be expressed when the wild-type allele has been deleted (and is no longer present to mask the recessive allele’s expression). The expression of a normally recessive mutation is referred to as pseudodominance, and it is an indication that one of the homologous chromosomes has a deletion.

Third, some genes must be present in two copies for normal function. When a single copy of a gene is not sufficient to produce a wild-type phenotype, it is said to be a haploinsufficient gene. A series of X-linked wing mutations in Drosophila is known as Notch. These mutations often result from chromosome deletions. Notch deletions behave in a dominant manner: when heterozygous for a Notch deletion, a fly has wings that are notched at the tips and along the edges (Figure 6.10). The Notch mutation is therefore haploinsufficient. Females that are homozygous for a Notch deletion (or males that are hemizygous) die early in embryonic development. The Notch locus, which is deleted in Notch mutations, encodes 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 mutation because the loss of all copies of the Notch gene prevents normal development.