Chromosomes swap DNA to create variety in the gene pool, but disorders can result if the exchanged regions don't match up properly. Recent studies suggest genetic elements called mariner transposons stimulate such mismatching exchanges underlying disorders like Charcot-Marie-Tooth disease and hereditary neuropathy.
In a study published in the September issue of Genome Research, Lawrence Reiter, James Lupski (Baylor College of Medicine), and colleagues use fluorescent imaging to locate 109 mariner elements across the human genome, revealing potential undiscovered links between these elements and other hereditary human diseases.
The mariner transposon encodes for a protein that cleaves DNA and also acts as a cleavage target for this protein. Like all transposons, mariner elements can jump around the genome, excising and inserting themselves in different locations over time. These cleavage events may stimulate chromosomes to swap DNA, making the mariner a potential hotspot for genetic change - as well as genetic error. To examine the occurrence of mariner across the human genome, Reiter and colleagues designed fluorescent probes that bind to mariner elements and applied these probes to whole human chromosomes. The chromosomes developed fluorescent bands revealing the locations of mariner elements, some of which correspond to sites of known genetic disorders such as growth hormone deficiency and hemophilia A. This work provides the first, preliminary evidence that places mariner in the vicinity of these disparate human diseases. So it may be apt now to recall the words of Samuel Coleridge's ancient mariner: "And I had done a hellish thing/And it would work 'em woe."
Contact information:
James R. Lupski
Department of Molecular and Human Genetics
Baylor College of Medicine
Houston, TX 77030
Fax: (713) 798-5073
Email: jlupski@bcm.tmc.edu
Journal
Genome Research