New Mathematical Model Explains Variability in Mutation Rates Across the Human Genome

It turns out that the type, how frequent, and where new mutations occur in the human genome depends on which DNA building blocks are nearby, found researchers from the. Perelman School of Medicine at the University of Pennsylvania in an advanced online study published this week in Nature Genetics . "We developed a mathematical model to estimate the rates of mutation as a function of the nearby sequences of DNA 'letters' - called nucleotides - in the human genome," said senior author Benjamin F. Voight, PhD , an assistant professor in the department of Systems Pharmacology and Translational Therapeutics and the department of Genetics. "This new model not only provides clues into the process of mutation, but also helps discover possible genetic risk factors that influence complex human diseases, such as autism spectrum disorder." This study focuses on the probability that any given nucleotide in the human genome - one of the four letters (A, C, G or'T for adenine, cytosine, guanine or thymine) of the DNA alphabet - is changed. Voight focused on the simplest type of mutation, a "point" mutation in which a single letter is changed in a given sequence. Most of these changes - often called single nucleotide polymorphisms (SNPs), or "snips" - are usually not harmful to the functioning of the human body. Nevertheless, Voight examined why some sequences are more prone to mutate, whereas others are not.