T

4 The retrotransposon integrates into the host DNA at the new site.

"Y

Old copy of retrotransposon

New copy of retrotransposon

^ Replication fills in the gaps at the site of insertion and creates the flanking direct repeats.

that produces numerous tumors of the skin and nerves; it results from mutations in a gene called NF1. Collins and his colleagues found a copy of Alu in one of the introns of this man's NF1 gene. The Alu had caused an RNA splicing error, with the result that one of the exons was left out of the NF1 mRNA. The absence of the exon caused a shift in the reading frame and resulted in an abnormal protein, which eventually caused the neurofibromatosis. Examination of DNA from the man's mother and father revealed that the Alu sequence was not present in their NF1 genes — the insertion was new. Cases of hemophilia and muscular dystrophy also have been traced to mutations caused by transposition.

Because transposition entails the exchange of DNA sequences and recombination, it often leads to DNA rearrangements. Homologous recombination between multiple copies of transposons also leads to duplications, deletions, and inversions, as shown in FIGURE 11.21. The Bar mutation in Drosophila (see Figures 9.7 and 9.8) is a tandem duplication thought to have arisen through homologous recombination between two copies of a transposable element present in different locations on the X chromosome.

DNA rearrangements can also be caused by excision of transposable elements in a cut-and-paste transposition. If the broken DNA is not repaired properly, a chromosome rearrangement can be generated. If it is not repaired at all, the acentric fragment will be last, resulting in a deletion. This type of chromosome breakage led to the first discovery of transposable elements by Barbara McClintock (described below). She named the gene that appeared at these sites Dissociation because of the tendency for it to cause chromosome breakage and loss of a fragment.

The Regulation of Transposition

Many transposable elements move through replicative transposition and increase in number with each transposition. As the number of copies of the transposon increases, the rate of transposition increases because the concentration

Transposable genetic elements

Q Pairing by looping and crossing over between two transposable elements oriented in the same direction..

Deletion product a

.leads to chromosome deletion

Transposable genetic elements

Q Pairing by looping and crossing over between two transposable elements oriented in the same direction..

Deletion product

.leads to chromosome deletion

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