Xiaofan Jin, PhD
Investigating the Relationship Between Chromosomal Structure and Recombination During Meiosis
Recombination during meiosis is the process by which parental chromosomes exchange genetic material. Errors in this process lead to negative health outcomes, and variability in recombination rate also affects genome evolution. In mammals, most crossovers occur in hotspots defined by the PRDM9 protein, though PRDM9 binding sites are not all equally hot. Meiotic chromosomes adopt distinct 3D structural organization, suggesting that differences in 3D genome organization may be linked to variable recombination activity at hotspots. To explore this idea, this project applies an integrative bioinformatics approach combining recently published measurements of 3D chromosomal organization during meiosis (Hi-C) as well as measurements of recombination activity including double-strand break (DSB) and crossover activity at PRDM9 hotspots. By stratifying recombination hotspots by their DSB and crossover activity, patterns of chromosomal configuration favoring recombination activity can be identified. The subsequent development of statistical models will then allow for the joint assessment of the contributions of different chromosomal structure variables to recombination activity. Collectively, these findings establish which aspects of chromosomal architecture are related recombination activity.
I am grateful to the PhRMA Foundation for supporting my research. The Postdoctoral Fellowship in Informatics has given me the opportunity to focus on my research project over the past year and provided me with the time and space to learn several key skills for analyzing modern genomic datasets. My development as a researcher has undoubtedly benefited from the experience made possible through the fellowship.