RGD Reference Report - Comparative mapping of distal murine chromosome 11 and human 17q21.3 in a region containing a modifying locus for murine plasma von Willebrand factor level. - Rat Genome Database

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Comparative mapping of distal murine chromosome 11 and human 17q21.3 in a region containing a modifying locus for murine plasma von Willebrand factor level.

Authors: Mohlke, KL  Purkayastha, AA  Westrick, RJ  Ginsburg, D 
Citation: Mohlke KL, etal., Genomics 1998 Nov 15;54(1):19-30.
RGD ID: 1549573
Pubmed: PMID:9806826   (View Abstract at PubMed)
DOI: DOI:10.1006/geno.1998.5553   (Journal Full-text)

Type 1 von Willebrand disease (VWD) is a common inherited disorder characterized by mild to moderate bleeding and reduced levels of von Willebrand factor (VWF). An animal model for human type 1 VWD, the RIIIS/J mouse strain, exhibits a prolonged bleeding time and reduced plasma VWF levels. We have previously mapped the defect in RIIIS/J to distal mouse Chr 11, distinct from the Vwf locus on Chr 6. This locus, Mvwf, was localized to an approximately 0.5-cM interval, tightly linked to Gip, distal to Ngfr, and proximal to Hoxb. We have now used these genetic markers to construct a contig of yeast and bacterial artificial chromosomes and bacteriophage P1 clones spanning the approximately 300-kb Mvwf nonrecombinant interval. In a comparative mapping approach, mouse homologues of mapped human expressed sequence tags (ESTs) were localized relative to the candidate interval. Twenty-one sequence-tagged sites and ESTs from the corresponding human syntenic region 17q21.3 were ordered using the high-resolution Stanford TNG3 radiation hybrid panel. Based on the resulting radiation hybrid map and our mouse genetic and physical maps, the order of human and mouse genes in a >0.7-cM region appears to be conserved. Six genes localized to the Mvwf nonrecombinant interval by comparative mapping included orthologs of GNGT2, ATP6N1, and a nuclear domain protein. Seven other genes or ESTs were excluded from the candidate interval, including orthologs of PHB, PDK2, a speckle-type protein, and a UDP-galactose transporter. Using exon trapping, 10 additional putative expressed sequences were identified within the Mvwf nonrecombinant interval, including a previously cloned murine glycosyltransferase as well as exons showing sequence similarity to genes for Caenorhabditis elegans and Saccharomyces cerevisiae predicted proteins, an Arabidopsis thaliana ubiquitin-conjugating enzyme, and a Gallus gallus mRNA zipcode-binding protein. Further characterization of these putative genes could identify the dominant mutation responsible for low plasma VWF levels in RIIIS/J mice. These data may also aid in the localization of other disease loci mapped to this region, including the gene for tricho-dento-osseous syndrome and a murine locus for susceptibility to ozone-induced acute lung injury.

Objects referenced in this article
Gene Atp6v0a1 ATPase, H+ transporting, lysosomal V0 subunit A1 Mus musculus
Gene Gip gastric inhibitory polypeptide Mus musculus
Gene Mrpl27 mitochondrial ribosomal protein L27 Mus musculus
Gene Pdk2 pyruvate dehydrogenase kinase, isoenzyme 2 Mus musculus
Gene Phb1 prohibitin 1 Mus musculus
Gene Phospho1 phosphatase, orphan 1 Mus musculus
Gene Scrn2 secernin 2 Mus musculus
Gene Spop speckle-type BTB/POZ protein Mus musculus

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