Analysis of de novo germline genome mutations

Abstract

Gene mutations are permanent alterations in sections of DNA sequences called genes. This causes a significant and distinguishable change in the base sequence of the affected DNA. They are changes to the base sequence that can occur spontaneously or in response to cellular damage and can vary greatly in size and position, ranging from a single base pair mutation, to changes that span segments of chromosomes, across several genes. Mutations in somatic (non-reproductive) cells are not passed on to the next generation, however germline mutations can occur in germ line cells that can produce egg and sperm, thus causing changes to the basic genome to become fixed in the DNA for future generations to come. This article focuses on germline mutations that are of particular interest to Ohno and her team. Many of these mutations - so called de novo mutations - are genetic alterations present for the first time in one family member as a result of a variation or mutation in a germ cell in either an egg or sperm of one of the parents. DNA repair systems allow for many of the mutations to be prevented and, in reality, only a low level of them become carried forward in the genome. Ohno and her team recognise the causes of germline mutation and are seeking to understand the implications of mutation, with a view to establishing how they may evolve and the possibilities for our future selves. The current human genome is a result of amassed mutations that have accumulated in our genome and driven it along certain pathways to yield what we are now. Ohno is currently working with gene-modified mice but the work is transferable to any mammalian genome, including humans to determine a possible future pathway.