"Our study addresses a fundamental issue with regards to the majority of the human genome that is non-coding in nature, and its potential impact on human health," explains Dr. Gabriela Loots, a scientist in the Department of Genome Biology at Lawrence Livermore National Laboratory who headed the study. "Non-coding regions located far away from the genes they regulate are critical for normal gene expression and are capable of leading to dramatic abnormal phenotypes if altered or deleted."
Van Buchem disease is a rare hereditary disorder of the skeletal system that is characterized by progressive osteosclerosis, particularly in the skull and mandible, but also in the clavicles, ribs, and diaphyses of long bones. Consequences of this increased bone mass usually include facial distortions and pinching of cranial nerves, and the increased nerve pressure often leads to deafness and blindness. Onset of the disease generally occurs during childhood and is manifested only in individuals carrying two copies of the mutant allele.
The locus responsible for Van Buchem disease was previously mapped to the short arm of human chromosome 17 near the gene sclerostin (or SOST), whose protein product functions as a negative regulator of bone formation. Mutations in the protein-coding regions of SOST are known to be responsible for sclerosteosis, another genetic disorder with attributes similar to Van Buchem disease. Because SOST was therefore a strong causal candidate for Van Buchem disease, scientists screene
Contact: Maria A. Smit
Cold Spring Harbor Laboratory