SynthesisPLoS genetics2014
A loss of function screen of identified genome-wide association study Loci reveals new genes controlling hematopoiesis.
Synthesis in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- The Chromatin Remodeler Chd8 Regulates Hematopoietic Stem and Progenitor Cell Survival and Differentiation During Zebrafish Embryogenesis.International journal of molecular sciences · 2025Article
- Genome-Wide RADseq Reveals Genetic Differentiation of Wild and Cultured Populations of Large Yellow Croaker.Genes · 2023Article
- Quantifying the role of transcript levels in mediating DNA methylation effects on complex traits and diseases.Nature communications · 2022Article
- The cellular architecture and molecular determinants of the zebrafish fusogenic synapse.Developmental cell · 2022Article
- Zebrafish ParalogsJournal of developmental biology · 2021Article
- Induction of human hemogenesis in adult fibroblasts by defined factors and hematopoietic coculture.FEBS letters · 2019Article
- Sphingolipid dysregulation due to lack of functional KDSR impairs proplatelet formation causing thrombocytopenia.Haematologica · 2019Article
- Single-cell RNA-sequencing uncovers transcriptional states and fate decisions in haematopoiesis.Nature communications · 2017Article
- Mutations in tropomyosin 4 underlie a rare form of human macrothrombocytopenia.The Journal of clinical investigation · 2017Article
- Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types.Genome research · 2017Article
- Single-Cell RNA-Sequencing Reveals a Continuous Spectrum of Differentiation in Hematopoietic Cells.Cell reports · 2016Article
- Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases.Frontiers in genetics · 2016Article
- From GWAS to function: lessons from blood cells.ISBT science series · 2016Article
- Mechanical vessel injury in zebrafish embryos.Journal of visualized experiments : JoVE · 2015Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
The formation of mature cells by blood stem cells is very well understood at the cellular level and we know many of the key transcription factors that control fate decisions. However, many upstream signalling and downstream effector processes are only partially understood. Genome wide association studies (GWAS) have been particularly useful in providing new directions to dissect these pathways. A GWAS meta-analysis identified 68 genetic loci controlling platelet size and number. Only a quarter of those genes, however, are known regulators of hematopoiesis. To determine function of the remaining genes we performed a medium-throughput genetic screen in zebrafish using antisense morpholino oligonucleotides (MOs) to knock down protein expression, followed by histological analysis of selected genes using a wide panel of different hematopoietic markers. The information generated by the initial knockdown was used to profile phenotypes and to position candidate genes hierarchically in hematopoiesis. Further analysis of brd3a revealed its essential role in differentiation but not maintenance and survival of thrombocytes. Using the from-GWAS-to-function strategy we have not only identified a series of genes that represent novel regulators of thrombopoiesis and hematopoiesis, but this work also represents, to our knowledge, the first example of a functional genetic screening strategy that is a critical step toward obtaining biologically relevant functional data from GWA study for blood cell traits.
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