Edit molecule mutation caused deadly primordialer

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Fetuses with defects in a molecular machine that works use information cells make proteins to a rare form of dwarfism, according to a new study led by researchers at the Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard j. Solove Research Institute (OSUCCC - James) develop.

Deficiency, triggered by a small mutation microcephaly with microcephalic Primoridal dwarfism caused type 1 (MOPD1), a rare developmental disorder, which significantly slows growth in the womb and caused severe brain and organ defects, deformities of the arms and legs, and death in infancy or childhood. "Primordialer" is short, which begins before birth.

The results could be a test for people who unknowingly carry a copy of the mutation to a better understanding of RNA Splicing and whether this type mutations that occur within an individual's life to the development of cancer or other diseases.

The study appears in the April 8 issue of the journal Science.

"Our results that smaller intron plays splicing crucial point in the human development", says study leader Dr. Albert de la Chapelle, Professor of medicine and co-leader of the OSUCCC James molecular biology and cancer genetics program. "The RNA Splicing, one of the most basic molecular is events in the cells".

The genetic information in an individual DNA stored is typically used by cells, to make proteins. This process begins when the information in a gene as one long beach (mRNA) is copied from messenger RNA.

Then non-essential elements of the mRNA, regions called introns, will produce, mRNA to the tires. The introns are molecular machines called Spliceosomes, which the free ends of the cut mRNA back together again join cut out.

There are two types of Spliceosomes, major and minor versions. Smaller Spliceosomes account for less than 1 percent of all splicing, but they still affect hundreds of genes in the human genome. This study shows that defects in smaller Spliceosomes can have profound consequences.

"Who can inherit two defective copies of the gene for this important component of the minor Spliceosome not efficiently from minor class of introns splicing, and this leads seen to the developmental defects in MOPD1," says Dr. Albert de la Chapelle.

Dr. Albert de la Chapelle and his colleagues discovered that the mutation is in a gene called RNU4ATAC, which occurs on chromosome 2. However, proved unusual nature and location to the reach the gene this discovery due to extremely difficult.

The search began, as the OSUCCC - James researchers learned that several children with severe, unnamed disorder in Ohio's Amish population was born. She identified the disease as MOPD I and worked for several years to determine where in the genome of the responsible gene, however, was found without success.

A break came when she used a strategy of called homozygoter mapping. This reduces the gene location in an area of chromosome 2, a region containing several known genes. Sequencing and study of these genes spent the researchers several years, but no likely candidates among them uncover their work.

Only when deep state-of-the-art next generation used the researchers sequencing technologies they identify RNU4ATAC and know that it was an unusual gene. Rather than the production of a protein, it encodes a special type of molecule called a "SNRNA." In addition, they learned that the unusual molecule a Spliceosome belonged.

In collaboration with Dr. Richard Padgett and other specialists in RNA Splicing at the Cleveland Clinic, the team has shown that the mutations splicing efficiency by 90% reduced.

"Now we call for clinicians around the world for samples that we can test of children and their families, who are suspected to suffer from MOPD1 or similar conditions," says de la Chapelle. "This research can help you determine us, unwittingly perform what family members can a copy of a harmful mutation, and to understand how these mutations can have consequences as serious developmental disorders."

Source:
Darrell E. Ward
Ohio State University Medical Center