A tool that could help scientists identify the new, potentially dangerous mutations in their genes has been described by researchers at MIT and UC Santa Cruz.
The discovery, published in Nature Communications, was made possible by a discovery of a rare and rare-in-nature gene mutation.
The mutation, found in the human genome, caused a change in how the protein responsible for making RNA, called cAMP-activated protein kinase, interacts with the body’s cell membrane, preventing it from replicating.
“The gene mutation affects proteins called c-AMP kinases,” said lead author Dr Robert A. Caulfield, an assistant professor of biological engineering at MIT.
“In most cases, these proteins are made up of one or more strands of DNA and bind to each other to form proteins that then assemble into larger molecules.
But some mutations are more like the two strands of strands of one DNA molecule that form the backbone of RNA.”
The mutation was first spotted in the genomes of two separate individuals and was confirmed by sequencing.
Dr Caulfields team analysed the mutation to identify a protein called SLC6A4, which is a common protein involved in regulating how RNA is folded into a protein-sized molecule.
This protein was only found in a handful of genes, and the researchers believe that the mutation can be found in all of the major human genes involved in RNA processing.
“This discovery opens up new avenues of investigation for scientists who study gene mutation and gene regulation,” said Caulfonds team lead author Shari G. Johnson, an associate professor of medicine and of biology at UC Santa Barbara.
“We’ve found a mutation that allows a specific protein in the body to bind to other proteins that bind to RNA, thus preventing it to replicate,” said Johnson.
“By sequencing the human DNA of the affected individuals, we were able to find a mutation in the SLC5A1 gene that was not present in the two other affected individuals.”
The scientists also found a gene mutation that causes a variant in the protein that the body makes to make cAMP, which can cause damage to the body.
“Our findings also suggest that it may be possible to develop drugs that block these genes, such as a protein that blocks the binding of SLC3A4 to other molecules,” Johnson said.
This discovery, like many others in the field of gene mutations, has its roots in the work of Dr Paul A. Hoerth, a professor of molecular genetics at UCSB.
“I first discovered this mutation about 20 years ago and used it to identify some mutations in genes that had already been known about,” said Hoerths co-author Dr Thomas F. Schmid, an Assistant Professor of Genetics at UC San Diego.
“However, I knew very little about the genetic basis of this mutation.
Hoers discovery led me to discover that the gene mutation is part of a larger set of genes that have similar effects on DNA structure and function.
So it seemed logical that this gene mutation was part of that larger set.”
Researchers from the Center for Genomic Medicine at UC Berkeley and UC Davis have also contributed to this discovery, which was published in the journal Nature Communications.###