Scientists Vivian Cheung and Warren Ewens from the University of Pennsylvania have developed a new approach for the diagnosis of medical disorders that are inherited in a recessive manner.
Their method is based on identifying subtle but distinct differences in genome-wide expression profiles using microarray technology. An article describing the approach appears online this week in the journal Genome Research.
As a model for their work, Cheung and Ewens used a rare recessive disease known as Nijmegen breakage syndrome (NBS). Only one gene - called NBS1 - is known to be causative for NBS, although there are multiple disease-initiating variants of this gene in different human populations. Individuals who possess deleterious mutations in both copies of NBS1 exhibit reduced head sizes, slowed growth rates, immunodeficiency, and a predisposition to cancer. Heterozygous carriers - who possess only one copy of the causative gene variant - appear normal, although some reports have suggested that heterozygotes may have an increased risk of cancer.
Using microarray technology, which simultaneously ascertains the expression patterns of thousands of genes, Cheung and Ewens discovered that heterozygous carriers of NBS exhibited distinct gene expression patterns when compared to controls. Of 3,928 genes that were expressed in the NBS carriers and controls, 520 consistently exhibited differences between the two groups.
Cheung and Ewens identified a set of 16 genes whose expression patterns could reliably discriminate between carriers and non-carriers of NBS. The genes could also distinguish carriers of NBS from carriers of a closely related syndrome known as ataxia telangiectasia. Therefore, these 16 predictive genes can be used to develop clinical tests to identify carriers of NBS.