Royal Society Francis Crick Lecture by Dr Matthew Hurles on 17 October 2013. One of the greatest surprises of human genetic research has been the degree to which healthy people vary in the number of genes in their genomes, as a result of gains and losses of large segments of DNA. Generating comprehensive maps of where these variants exist in our genomes has enabled us to identify large common genetic variants that influence our susceptibility to common diseases such as diabetes, as well as to discover large rare genetic variants that can cause a wide range of rare disorders. Dr Hurles will discuss how his investigations of this previously under-appreciated form of genetic variation have helped to shape our current understanding of both the genetic causes of disease, and the mutation processes that edit the genome as it is passed from one generation to the next. As a post-doctoral research fellow in population genetics at the University of Cambridge, Dr Hurles was the first to establish the molecular mechanism underlying a recurrent deletion of part of the Y-chromosome, which causes male infertility. In 2003, Dr Hurles joined the Wellcome Trust Sanger Institute in Cambridge. Dr Hurles is currently coordinating efforts to apply genome-wide resequencing methods to improve the diagnosis of rare diseases and understand the factors influencing rates of germline mutation. The Francis Crick Lecture is given annually in any field in the biological sciences. Preference is given to genetics, molecular biology and neurobiology, the general areas in which Francis Crick worked, and to fundamental theoretical work, which was the hallmark of Crick's science. Dr Matthew Hurles was awarded the 2013 Francis Crick Lecture for his outstanding contributions to understanding structural variation in the human genome, the mechanisms that cause this variation and its medical and evolutionary consequences. Video cover image: © Svisio/iStock.