May 17, 2006
Most inherited genetic diseases have been defined years ago by the carefully documented but largely descriptive clinical observations of physicians and scientists. But with the advent of more powerful laboratory tools, scientists have circled back in recent years to attempt to define these and other as-yet unnamed genetic conditions according to the specific DNA alterations that underlie them. Among these alterations are deletions or duplications of short stretches of DNA that can throw areas of the genome out of frame, alter the production of essential developmental proteins, and give rise to complex congenital syndromes that may include craniofacial disorders. In cataloguing these so-called microdeletions and microduplications, however, scientists have run into a major technical difficulty. Current clinical tools still lack the needed submicroscopic resolution to read through a person’s DNA and rapidly detect these often subtle chromosomal rearrangements.
Now, an NIDCR grantee and colleagues have taken an important and practical step forward to solve this research problem. In the May issue of the journal Human Mutation, the scientists report they could rapidly detect submicroscopic chromosomal rearrangements that give rise to multiple congenital anomalies. They did so using high density oligonucleotide microarrays, a laboratory tool that provides a comprehensive, detailed snapshot of a person’s genome. This genomic profile can be compared to control samples to determine if there have been gains or losses of chromosomal material. Among their various proof-of-principle experiments, the scientists scanned the DNA of 10 patients with multiple congenital anomalies of unknown origin. The microarray technology enabled the scientists to identify previously unknown microdeletions in two patients with craniofacial differences that likely underlie their conditions. As the scientists noted, what’s particularly exciting about this paper is the microarray technology already is commercially available and ready for application. The authors also noted that by identifying these chromosomal changes, insight may be gained into the appropriate medical care for these patients as well as the overall genetic program of facial development.