Exploring large-scale genetic mosaicism and its relationship to hematological malignancies

Genetic variation naturally occurs among the cells of a single individual as a result of somatic mutation. Some somatic mutations proliferate to high frequency within an individual, producing a phenomenon known as clonal mosaicism. Cancer is an extreme example, but mosaicism also exists in cancer-free individuals. We aim to study the distribution of chromosome-scale mosaic aberrations in UK Biobank samples. We then aim to investigate the relationship between these aberrations and diseases of the blood, with a focus on chronic lymphocytic leukemia (CLL). This work will improve our understanding of clonal expansions in the blood, a phenomenon present in many aging individuals that is closely related to leukemia. By investigating mosaicism in a very large prospective cohort, this research may potentially identify signatures of pre-cancerous mosaic events and/or enable earlier diagnoses of leukemia. We will analyze allelic intensity data from genotyped blood samples to identify imbalances in the frequencies of maternally and paternally derived chromosomal segments. Such imbalances indicate large-scale chromosomal aberrations (i.e., losses and gains of long segments of DNA) that have proliferated to significant frequency in the blood. We will then compare incidences of these events to data on blood counts and cancer outcomes. We will analyze the full cohort.