Cell and Developmental Biology Seminar Series: Genome diversification and stability in the human germline
13:30 - 14:30
Eva R Hoffmann
Department of Cellular and Molecular Medicine , University of Copenhagen / Copenhagen, Denmark
Max-Planck-Institut für biophysikalische Chemie (MPIBPC)
AI building, large seminar room
Department of Meiosis
We have long appreciated that genetic diversity provides the basis for evolutionary processes and also influence the health of individuals. Human genetic diversity is studied predominantly in populations, however, this is just a small fraction of what we suspect is generated in the germline. In the lab, we are interested in exploring the genome repertoire that is generated in eggs and sperm, and understanding their importance for human health. Using single cell genomics to obtain DNA sequences from all products of meiosis, which reduces chromosome content by one half in our germ cells, we are mapping recombination patterns and their importance for chromosome segregation in human oocytes. We further seek to understand fine scale changes to the genome, such as gene conversions, which occur when a single nucleotide polymorphism (SNP) segregates 3 to 1 instead of the Mendelian ratio of 2 to 2. Gene conversions arise from the repair of double-strand breaks and provide a footprint of where chromosomes interacted during their pairing processes, prior to segregation. To this end, we use machine learning algorithms to improve high precision genotyping after a single genome has been amplified and sequenced. Finally, I will present a new model for de novo chromosome formation. We have detected chromosome breaks in human oocytes and propose that the breaks may precede large scale chromosome deletions and translocations in human. We propose two pathways for the generation of chromosome breaks, based in part on a haploinsufficient mouse model (Smc6) and budding yeast data. In summary, the technological advances in single cell genomics have allowed us to start probing genome repertoire directly in the human germ cells and therefore trace the origins and mechanisms of chromosome evolution.