A translocation entails the movement of genetic material between nonhomologous chromosomes (see Figure 6.4d) 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.

159

In a nonreciprocal translocation, genetic material moves from one chromosome to another without any reciprocal exchange. Consider the following two nonhomologous 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•CDQRS and MN•OPEFG.

EFFECTS OF TRANSLOCATIONS Translocations can affect a phenotype in several ways. First, they can physically link genes that were formerly located on different chromosomes. These new linkage relations may 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.

Second, the chromosome 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 that, when mutated, causes neurofibromatosis on chromosome 17, but its precise location was unknown. Geneticists later narrowed down the location when they 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. DNA from the regions around the breaks was sequenced, eventually leading 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 metacentric chromosome with two long arms and another chromosome with two very short arms (Figure 6.15). The smaller chromosome is often lost because very small chromosomes do not have enough mass to segregate properly during mitosis and meiosis. The result is an overall reduction in chromosome number. As we will see, Robertsonian translocations are the cause of some cases of Down syndrome, a disorder discussed later in this chapter.

TRANSLOCATIONS IN MEIOSIS The effects of a translocation on chromosome segregation in meiosis depend on the nature of the translocation. Let’s consider what happens in an individual heterozygous for a reciprocal translocation. Suppose that the original chromosomes were AB•CDEFG and M•NOPQRST (designated N1 and N2, respectively, for normal chromosomes 1 and 2) and that a reciprocal translocation takes place, producing chromosomes AB•CDQRST and M•NOPEFG (designated T1 and T2, respectively, for translocated chromosomes 1 and 2). An individual heterozygous for this translocation would possess one normal copy of each chromosome and one translocated copy (Figure 6.16a). Each of these chromosomes contains segments that are homologous to segments of two other chromosomes. Thus, when the homologous sequences pair in prophase I of meiosis, crosslike configurations consisting of all four chromosomes form (Figure 6.16b). Whether viable or nonviable gametes are produced depends on how the chromosomes in these crosslike configurations separate. Only about half of the gametes from an individual heterozygous for a reciprocal translocation are expected to be functional, so these individuals frequently exhibit reduced fertility.

160