Leveraging long range phasing to detect mosaicism in blood at ultra-low allelic fractions

Dept. of Medicine and Division of Genetics, Brigham and Women's Hospital, Harvard Medical School; Ó³»­´«Ã½

McCarrol Lab, Ó³»­´«Ã½; Dept. of Genetics, Harvard Medical School

What would you do with 500,000 near-perfectly phased genomes? One answer (we welcome others!): harness this information to detect subtle imbalances between maternal and paternal allelic fractions in blood DNA -- the hallmark of clonal mosaic chromosomal alterations [1,2]. In this talk, we will describe how we phased the UK Biobank to chromosome-scale accuracy [3,4], developed HMM-based machinery to sensitively call mosaic alterations, and probed the data to reveal new insights into the causes and consequences of clonal hematopoiesis.

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