No two human beings are the same. Although we all possess the same genes, our genetic code varies in many places. And since genes provide the blueprint for all proteins, these variants usually result in numerous differences in protein function. But what impact does this diversity have? Bioinformatics researchers at Rutgers University and the Technische Universitaet Muenchen (TUM) have investigated how protein function is affected by changes at the DNA level. Their findings bring new clarity to the wide range of variants, many of which disturb protein function but have no discernible health effect, and highlight especially the role of rare variants in differentiating individuals from their neighbors.
The slightest changes in human DNA can result in an incorrect amino acid being incorporated into a protein. In some cases, all it takes is for a single base to be substituted in a person's DNA, a variant known as a single nucleotide polymorphism (SNP). "Many of these point mutations have no impact on human health. However, of the roughly 10,000 'missense' SNPs in the human genome that is, SNPs affecting the protein sequence at least a fifth can change the function of the protein," explains Prof. Yana Bromberg of the Department of Biochemistry and Microbiology at Rutgers University. "And in some cases, the affected protein is so important and the change so large that we have to wonder why the person with this mutation is still healthy."
Furthermore, two unrelated individuals have thousands of different mutations that affect proteins. Previously, scientists did not fully understand how this large number of mutations affects the coding sequences of DNA. To investigate these "silent" mutations, Bromberg joined forces with Rutgers colleague Prof. Peter Kahn and Prof. Burkhard Rost at TUM.
Silent mutations more significant than previously thought
"We found that many of the mutations are anything but silent," declares Rost, he
|Contact: Patrick Regan|
Technische Universitaet Muenchen