Journal article
Leukaemia disease genes: large-scale cloning and pathway predictions
Nature genetics, Vol.23(3), pp.348-353
11/1999
DOI: 10.1038/15531
PMID: 10610183
Abstract
Retroviral insertional mutagenesis in BXH2 and AKXD recombinant inbred mice induces a high incidence of myeloid or B- and T-cell leukaemia1,2 and the proviral integration sites in the leukaemias provide powerful genetic tags for disease gene identification. Some of the disease genes identified by proviral tagging are also associated with human disease3,4,5, validating this approach for human disease gene identification. Although many leukaemia disease genes have been identified over the years, many more remain to be cloned6. Here we describe an inverse PCR (IPCR) method for proviral tagging that makes use of automated DNA sequencing and the genetic tools provided by the Mouse Genome Project, which increases the throughput for disease gene identification. We also use this IPCR method to clone and analyse more than 400 proviral integration sites from AKXD and BXH2 leukaemias and, in the process, identify more than 90 candidate disease genes. Some of these genes function in pathways already implicated in leukaemia, whereas others are likely to define new disease pathways. Our studies underscore the power of the mouse as a tool for gene discovery and functional genomics.
Details
- Title: Subtitle
- Leukaemia disease genes: large-scale cloning and pathway predictions
- Creators
- Haifa Shen - Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development CenterAdam J Dupuy - Department of Genetics, Cell Biology and Development, University of Minnesota Cancer CenterDavid A Largaespada - Department of Genetics, Cell Biology and Development, University of Minnesota Cancer CenterJohn D Shaughnessy - Department of Medicine, University of Arkansas for Medical SciencesKaren L Himmel - Department of Genetics, Cell Biology and Development, University of Minnesota Cancer CenterNeal G Copeland - Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development CenterJiayin Li - Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development CenterNancy A Jenkins - Mammalian Genetics Laboratory, ABL-Basic Research Program, NCI-Frederick Cancer Research and Development CenterTakuro Nakamura - PRESTO, JST and Japanese Foundation for Cancer Research
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.23(3), pp.348-353
- DOI
- 10.1038/15531
- PMID
- 10610183
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 11/1999
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025473502771
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