Whole Genome Sequencing Application Developed for Mutation Discovery

The innovative methodology has the potential to reduce the time and effort required to identify mutations of biologic interest.

The researchers, from the Stowers Institute of Medical Research's (Kansas City, KS, USA) Hawley Lab and Molecular Biology Facility, mapped a fruit-fly mutation caused by the compound ethyl methanesulfonate (EMS) by determining the DNA sequence of the mutant fly's genome. The study's findings provide clues into the process of EMS mutagenesis and into gene conversion events involving balancer chromosomes--genetic tools used to prevent genetic recombination between homologous chromosomes during meiosis.

Model organisms such as fruit flies are used in research for studying both normal biologic mechanisms and human disease. Fruit fly genes can be inserted, deleted, or modified, and large numbers of flies can be randomly mutated to generate interesting phenotypes relevant to human disease. Finding the mutated gene responsible for a specific phenotype is labor-intensive and time-consuming, and many mutations that cause medically relevant phenotypes are not discovered. The new approach lowers the problem of finding mutations and greatly accelerates the discovery of genes important for human health.

"This approach will change the way fruit fly genetics is done,” said Scott Hawley, Ph.D., Investigator and coequal senior author of the study. "Traditional mapping approaches to identify mutations are inefficient procedures. Our whole-genome sequencing approach is fast and cost-effective. Among other potential uses, it also carries the potential to pinpoint inheritable molecular characteristics that are controlled by several genes at once.”

"The traditional mapping method could take months to years depending on the complexity of the phenotype,” said Karen Staehling-Hampton, Ph.D., managing director of molecular biology and coequal senior author of the research. "This advance will allow us to map mutations of interest in just a few weeks. The next-generation sequencing technology used for this project is extremely exciting. It will allow researchers to sequence genomes for a few thousand dollars, a cost unheard of just a few years ago. It will also enable them to take their science in new directions and answer new questions that were not possible with traditional sequencing technology.”

The study was published in the May 2009 issue of the journal Genetics.

Related Links:
Stowers Institute of Medical Research