Genetics of Myelodysplastic Syndrome: A Zebrafish Screen

Dana-Farber Cancer Institute, Boston MA

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Abstract

Mutagenesis screens in zebrafish have been shown to be a powerful way to identify critical genes in pathways of vertebrate blood development. The mutagenesis screen proposed here will uncover genes whose mutation leads to abnormal granulocytic cell development. Careful analysis of the blood lineages in mutant fish will determine whether the developmental defects are confined to the granulocyte lineage or affect multiple blood cell types. Our hypothesis is that a subset of these mutant fish will exhibit blood cell abnormalities similar to Myelodysplastic syndrome (MDS). MDS is a devastating disease in children and adults, that can affect several myeloid blood cell types and often progresses to acute leukemia. MDS is associated with specific chromosomal deletions, suggesting that genes within these regions are responsible, for the disease which have yet to be identified