Breakpoints are significant because they can lead to disruption or deletion of genes, as in Williams-Beuren syndrome (WBS), a developmental disorder that leads to physical and mental abnormalities. This syndrome is caused by deletion or inversion of DNA following genetic recombination, a process whereby a piece of DNA that lies between two highly homologous DNA segments is swapped for a similarly situated piece of DNA on another chromosome. By their very nature, duplications of DNA segments (duplicons) can provide the structural scaffold for the genetic recombination that leads to chromosome rearrangements, often with disastrous consequences (see ARF related news story).

Scherer and colleagues have previously shown that WBS is due to such a rearrangement on chromosome 7, and asked here whether duplicons sprinkled across the chromosome could also lead to other diseases. To test for duplicons, Scherer and colleagues compared the sequence of the chromosome with itself. They found 146 duplications comprising 5.3 percent of the entire chromosome, a ratio higher than in any other chromosome in the genome. From patient sequence data, the authors also pinpointed 440 loci where such rearrangements could occur on chromosome 7. But are any linked to disease?

Mapping breakpoints in autistic patients, the authors found three potential autism genes. One breakpoint, which disrupts a noncoding RNA transcript, coincided with a genetic rearrangement in a patient diagnosed with speech and language problems-the latter are common in autistic patients. Another breakpoint mapped near the FOXP2 gene, also linked to speech and language disorders, while a third was found in close proximity to the neuronal pentraxin-2 gene, which likely plays a role in synaptogenesis and could, therefore, be involved in autism. Currently, the authors are examining autism families for possible mutations in these genes.-Tom Fagan.

Reference:
Scherer SW, et.al. Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Abstract