A High-Resolution Genetic, Physical, and Comparative Gene Map of the Doublefoot (Dbf) Region of Mouse Chromosome 1 and the Region of Conserved Synteny on Human Chromosome 2q35 |
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Authors: | Christopher Hayes Andreas Rump Matthew R Cadman Mark Harrison Edward P Evans Mary F Lyon Gillian M Morriss-Kay Andr Rosenthal Steve D M Brown |
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Institution: | a Medical Research Council, Mammalian Genetics Unit and UK Mouse Genome Centre, Harwell, Didcot, Oxon. OX11 0RD, UK;b Genome Sequencing Centre, Institute of Molecular Biotechnology, Beutenbergstrasse 11, Jena, 07745, Germany;c Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK |
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Abstract: | The mouse doublefoot (Dbf) mutant exhibits preaxial polydactyly in association with craniofacial defects. This mutation has previously been mapped to mouse chromosome 1. We have used a positional cloning strategy, coupled with a comparative sequencing approach using available human draft sequence, to identify putative candidates for the Dbf gene in the mouse and in homologous human region. We have constructed a high-resolution genetic map of the region, localizing the mutation to a 0. 4-cM (±0.0061) interval on mouse chromosome 1. Furthermore, we have constructed contiguous BAC/PAC clone maps across the mouse and human Dbf region. Using existing markers and additional sequence tagged sites, which we have generated, we have anchored the physical map to the genetic map. Through the comparative sequencing of these clones we have identified 35 genes within this interval, indicating that the region is gene-rich. From this we have identified several genes that are known to be differentially expressed in the developing mid-gestation mouse embryo, some in the developing embryonic limb buds. These genes include those encoding known developmental signaling molecules such as WNT proteins and IHH, and we provide evidence that these genes are candidates for the Dbf mutation. |
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Keywords: | Abbreviations: DoublefootAbbreviations: genetic mappingAbbreviations: physical mappingAbbreviations: gene identificationAbbreviations: limb developmentAbbreviations: comparative sequencing |
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