SAN DIEGO—A project spearheaded at the University ofCalifornia, San Diego (UCSD), and brought East to Brown University on the backof a post doctoral student whose study prompted the work, has yielded a newonline software product called InvChecker, which provides a more accuratemethod of identifying genomic variations called microinversions.
A form of genetic mutation, microinversions occur when shortDNA sequences break away from a chromosome and subsequently reattach in thereverse direction. Ranging from a few dozen to as many as a few thousand basepairs can result in a string of code that ought to read ATTAGCCG to be invertedand read GCCGATTA. These microinversions have been implicated as genetic causesof certain diseases including infertility and muscular dystrophy.
Ben Raphael, a co-author of the study which recentlyappeared online in the Proceedings of the National Academy of Sciences says theoriginal work for his post-doctoral study began in a completely different areathen shifted to the study of microinversions.
"What we were trying to do was come up with a fine-grainedway of looking at genomic sequences," says Raphael, now an assistant professorof computer science at Brown. "Pavel [Pezner—a senior author of the study] andother collaborators had been involved inother whole-genome comparisons, and had seen that there are these chromosomalrearrangements that occur over evolutionary time." In so doing, Pezner andassociates had found regions of "symphony" or regions of the genome that areindentical in different species and allow researchers to chart an evolutionarypath.
But, Raphael notes, this work had been done on a much largerscale. What he—and lead author Mark Chaisson, a graduate student at UCSD'sJacobs School of engineering—sought to do, was create a software tool thatwould draw on the idea that microinversions are preserved over evolutionary time and are much easier to spot whencomparing the genomes of three or morespecies.
From this work was born InvChecker, Raphael says, animportant tool for researchers conducting comparative genomic studies to betterunderstand how genomes evolved over time.
While the tool's main audience would be researchersconducting evolutionary studies, Raphael sees the potential for InvChecker toaid drug discovery researchers as well. He says that researchers are beginningto appreciate more that human are not "99.9 percent identical because of theselarger scale [genomic] changes and duplicated pieces, deleted pieces andmissing pieces. "This is a rich new source of genetic material for allkinds of disease association studies," he says. "All of these changes are relatedto disease, in a sporadic sense, and effect how gene are expressed. So it is arich and more accurate source of information for people looking to study thesemuch smaller inversions."