RNA cluster deletion implicated in Prader-Willi syndrome
By Ruth SoRelle, M.P.H.
When all or part of a cluster of genetic material known as small nucleolar RNAs is deleted on the chromosome 15 inherited from the father, children are more likely to have the genetic disorder Prader-Willi syndrome, said researchers from Baylor College of Medicine in a report in the current issue of Nature Genetics.
"Prader-Willi syndrome is the first disorder known to be associated with the loss of these small nucleolar RNAs," said Arthur Beaudet, M.D., chair of molecular and human genetics at BCM and senior author of the report.
Short stature, obesity
Prader-Willi syndrome is characterized by short stature, obesity as a child, developmental delay and other disorders.
The loss of these small nucleolar RNAs is associated with these symptoms, said Beaudet. These RNAs are a departure from the best known role of RNAs, serving as the template for making protein. Instead, they guide chemical modifications of ribosomal RNAs, which are the decoders of the genetic message that results in the production of proteins. Proteins are the workhorses of a cell, carrying out most of its functions.
Genome of child with disorder
In a study involving the genome of a child with Prader-Willi syndrome, Beaudet and his colleagues found that a deletion of genetic material for a particular cluster of these small nucleolar RNAs called HBII-85 was associated with many of the symptoms attributed to Prader-Willi syndrome in this child.
Studies in mice by other investigators also suggested that the loss of these particular forms of RNA contributed to the problems associated with the disease, said Beaudet.
In an accompanying review of the research, Dr. Jo Peters of the Medical Research Council in Oxfordshire, United Kingdom, wrote, “Both the genetics and the phenotype (visible symptoms) of PWS (Prader-Willi syndrome) are complex, and identifying the gene(s) responsible has been a challenge, but we now have the answer."
Others who took part in this research include Trilochan Sahoo, Daniela del Gaudio, Jennifer R German, Marwan Shinawi, Sarika U. Peters, Richard E. Person and Sau Wai Cheung, all of BCM, and Adolfo Garnica of St. Francis Hospital in Tulsa, Okla.
Funding for this research came from the National Institutes of Health, the Mental Retardation and Developmental Disabilities Research Center and the Rare Disease Clinical Research Consortia.
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