Genetic variation underlies epigenomic variation and the consequences of DNMT3A mutation in hematopoietic stem cells
Accumulation of somatic mutations in genes including the DNA methyltransferase DNMT3A predisposes many, but not all, individuals to development of clonal hematopoiesis and acute myeloid leukemia (AML). We hypothesize that individual genetic variation underlies distinct epigenomic patterning, and that this variation alters susceptibility to the pathogenic consequences of DNMT3A mutations in hematopoietic stem cells (HSCs). Through a collaborative effort to assess epigenome variation in a genetically diverse model system, we performed an in-depth chromatin analysis of liver cells isolated from 8 classical and wild-derived inbred mouse strains that recapitulate the genetic diversity of the human population.
Source: Experimental Hematology - Category: Hematology Authors: Jennifer Trowbridge, Rebecca Bell, Catrina Spruce, Anna Tyler, Robyn Ball, Vivek Philip, Dan Gatti, Narayanan Raghupathy, Romy Kurasawe, Kira Young, Mary Ann Handel, Michael Stitzel, Gary Churchill, Kenneth Paigen, Petko Petkov, Gregory Carter Source Type: research
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