Translocations

A translocation entails the movement of genetic material between nonhomologous chromosomes (see Figure 9.5d) or within the same chromosome. Translocation should not be confused with crossing over, in which there is an exchange of genetic material between homologous chromosomes.

Human chromosome 4

Mill II III!Ill

Centromere

Pericentric inversion b

Chimpanzee chromosome 4 r~

Mill II IIIIIIIIH II

I 9.15 Chromosome 4 differs in humans and chimpanzees in a pericentric inversion.

In nonreciprocal translocations, genetic material moves from one chromosome to another without any reciprocal exchange. Consider the following two nonhomol-ogous chromosomes: AB^CDEFG and MN^OPQRS. If chromosome segment EF moves from the first chromosome to the second without any transfer of segments from the second chromosome to the first, a nonreciprocal translocation has taken place, producing chromosomes AB^CDG and MN^OPEFQRS. More commonly, there is a two-way exchange of segments between the chromosomes, resulting in a reciprocal translocation. A reciprocal translocation between chromosomes AB^CDEFG and MN^OPQRS might give rise to chromosomes AB^CDQRG and MN^OPEFS.

Translocations can affect a phenotype in several ways. First, they may create new linkage relations that affect gene expression (a position effect): genes translocated to new locations may come under the control of different regulatory sequences or other genes that affect their expression— an example is found in Burkitt lymphoma, to be discussed later in this chapter.

Second, the chromosomal breaks that bring about translocations may take place within a gene and disrupt its function. Molecular geneticists have used these types of effects to map human genes. Neurofibromatosis is a genetic disease characterized by numerous fibrous tumors of the skin and nervous tissue; it results from an autosomal dominant mutation. Linkage studies first placed the locus for neurofibromatosis on chromosome 17. Geneticists later identified two patients with neurofibromatosis who possessed a translocation affecting chromosome 17. These patients were assumed to have developed neurofibromatosis because one of the chromosome breaks that occurred in the translocation disrupted a particular gene that causes neu-rofibromatosis. DNA from the regions around the breaks was sequenced and eventually led to the identification of the gene responsible for neurofibromatosis.

Deletions frequently accompany translocations. In a Robertsonian translocation, for example, the long arms of two acrocentric chromosomes become joined to a common centromere through a translocation, generating a metacen-tric chromosome with two long arms and another chromosome with two very short arms ( FIGURE 9.16). The smaller chromosome often fails to segregate, leading to an overall reduction in chromosome number. As we will see, Robertsonian translocations are the cause of some cases of Down syndrome.

The effects of a translocation on chromosome segregation in meiosis depend on the nature of the translocation. Let us consider what happens in an individual heterozygous for a reciprocal translocation. Suppose that the original chromosome segments were AB^CDEFG and MN^OPQRS (designated N1 and N2), and a reciprocal translocation takes place, producing chromosomes AB^CDQRS and MN^OPEFG (designated T1 and T2). An individual heterozygous for this translocation would pos-

The short arm of one acrocentric chromosome.

Break points

The short arm of one acrocentric chromosome.

Break points

Robertsonian translocation

Metacentric chromosome

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