Researchers discover novel genomic disorders

Researchers at the University of Washington and The Howard Hughes Medical Institute have discovered several new genetic causes of mental retardation, according to a study published online August 13 in Nature Genetics. One form of retardation, caused by a large deletion that spans six genes on chromosome 17, has characteristic facial, behavioral, and other physical features that can aid clinicians in identifying similar syndromes.

Working with colleagues in the UK and US, the researchers screened 290 children with mental retardation and identified several abnormal genetic events. The researchers were able to pinpoint the region of the specific deletion using NimbleGen's high-resolution CGH microarrays. “The ability of NimbleGen to rapidly generate custom-designed, high-density oligo arrays targeted to the specific chromosomal regions we were interested in provided us the key data in our study,” stated Dr. Andrew Sharp, Senior Fellow and Rosetta Fellow of the University of Washington and first author on the paper. “Having these tools in hand gave us, in a single experiment, what would otherwise have taken months of work using conventional methods, and allowed unprecedented insight into the underlying biology and mechanism of genomic disease.”

The deletion on chromosome 17 was seen in multiple children. Based on current data, this deletion potentially accounts for ~1% of cases of mental retardation, making it one of the most common genetic causes of mental retardation. The deletion, encompassing several genes, is associated with a region of DNA that is commonly reversed (or inverted) in one in five people of European descent. Intriguingly, this deletion seems to occur preferentially among children of individuals who carry the inversion.

The research was based on the hypothesis that the genome contains hotspots that are prone to instability and thus play a key role in the occurrence of genomic disorders. These hotspots are flanked on each side by large, repetitive regions of DNA, termed “segmental duplications”. It is because of the repetitive nature of these regions that, during replication, the genome can become “confused” and duplicate, reverse, or delete itself within these regions.