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USING FORWARD GENETICS TO GAIN NEW INSIGHTS INTO HAEMATOPOIESIS

Carradice, Duncan1,2,3

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Pathology - Journal of the RCPA: 2010 - Volume 42 - Issue - p S38
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Despite progressive advances in understanding of the genetic mechanisms regulating haematopoiesis, a complete picture of the genetic mechanisms controlling haematopoietic cells remains elusive. Many of the advances in this field have been made by examining the phenotypes of mice with targeted disruption of genes thought to have a role in blood cell development (gene “knockout” mice). As the human genome contains nearly 30,000 protein coding genes, in addition to non‐coding microRNAs and regulatory regions, deciding which part of the genome to examine for its role in haematopoiesis must depend on prior knowledge and is never likely to reveal the full picture (a reverse genetic approach). An alternative method is to approach the problem from the opposite direction. Using a non‐targeted, but more simple approach to genome disruption (e.g., chemical mutagenesis), an extensive panel of mutants can be examined for a phenotype of interest within haematopoiesis (forward genetics). The contribution of forward genetics to the understanding of haematopoiesis will be discussed, focusing on the complementary roles of forward genetic screens in different vertebrate models.

© 2010 Royal College of Pathologists of Australasia