Gene-Centric Functional Dissection of Human Genetic Variation Uncovers Regulators of Hematopoiesis

Follow-up work was performed for SF3A2, a gene among the hits identified in a red blood cell trait GWAS-informed shRNA screen. Differential splicing effects were assayed to investigate resulting effects on the differentiating erythroid cell spliceome and explore potential modifier relationships with other known splicing defects associated with human disease. Overall design: Examination of differential splicing events resulting from knockdown of splicing factor 3a subunit 2 (SF3A2) in three unique donor CD34+ cells populations undergoing erythroid differentiation. Two shRNA targeting SF3A2 were tested, along with a negative control shRNA targeting luciferase (which should not be expressed) using paired-end sequencing.

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Nandakumar SK, McFarland SK, Mateyka LM, Lareau CA, Ulirsch JC, Ludwig LS, Agarwal G, Engreitz JM, Przychodzen B, McConkey M, Cowley GS, Doench JG, Maciejewski JP, Ebert BL, Root DE, Sankaran VG