From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. In this session, we will hear about recent advances in studying somatic mutations across normal tissues, which has demonstrated differences in mutation rates, a prevalence of disease-associated mutations in normal cells and a variable preponderance of mutational processes. Many of these recent advances are fueled by development of novel technologies to detect mutations, which will feature heavily in this session.

Mutations acquired through life in germ cells have the potential to be passed on to the next generation, which - over time - will manifest as genetic variation between individuals and populations, affecting gene expression and regulation, and underpinning many genetic diseases. In this session, we will focus on the mutational processes and somatic evolution in germ cells, the evolutionary forces shaping inherited genetic variation and genetic disease.

As somatic mutations are reliably inherited by daughter cells, they can be used to retrace lineages of cells and reconstruct phylogenies, reflecting early development, tissue renewal and age-related aberrances. While the vast majority of somatic mutations do not alter the phenotypes of cells, some mutations affect key genes that grant cells a selective advantage and lead to expansions of these lineages. Over time, our tissues become patchworks of mutant clones. These clonal expansions, especially clonal hematopoiesis, have been associated with diverse disease risks, such as cancers, cardiovascular disease and neurodegenerative disorders. In this session, we will hear about efforts to trace the lineages of cells and quantify somatic evolution.

Genetic variation drives the origins of species and has generated the abundance of life on earth. The study of genetic variation between and within species, as well as mutational processes operating on individuals of a species, can reveal fundamental biology with profound implications for human genetic studies. In this session, our speakers will discuss a variety of topics including genetic adaptations of species to disease pressures and their environment and mutation rates across diverse species with consequences for our understanding of aging.

While most somatic mutations are functionally neutral, some can profoundly alter a cell’s phenotype and are associated with disease. Cancer is the best-known example, but other diseases including chronic liver disease, Huntington’s disease, and neurodevelopmental disorders are caused by somatic mutation or influence the selection of somatic clones. In this session, we will focus on how somatic mutations and evolution can lead to dysfunction, disease and treatment resistance, and why different populations are at different risk of somatic mutation-related diseases, and the challenges in diagnosing mosaic or tissue-specific disease.