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    Mutations and Polymorphisms in the Mouse: Detection and Characterization Using Restriction Endonucleases

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    Authors
    Cobb, Ronald
    Issue Date
    1986-06
    URI

    http://hdl.handle.net/10675.2/622285
    
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    Abstract
    Three heritable mutations, induced by treatment with either x-rays or triethylenemelamine, result in m~use models. for human alphathalassemia. In each mutation, the adult alpha-globin genes and the embryonic alpha-like x-globin gene on the same chromosome (the genes that comprise the mouse Hba locus on Chromosome 11) are no longer expressed. The use of several clones,. which contain .sequences homologous to the mouse Hba locus, as hybridization prob_es p·roved that each of the mutated chromosomes has a deletion of at least 40 kilobases (kb) that includes the three· mouse alpha-like globin genes. These same clones were used to discover restriction fragment length polymorphisms at both the 5' and 3' ends of the mouse Hba locus. In addition to the restriction fragment l~ngth polymorphisms discovered. at the Hba.locus, a new restriction fragment length polymorphism was found closely linked to the locus that controls induction of the chemical carcinogen-metabolizing enzymes in mice (the aryl .hydrocarbon hydroxylase or Ah locus). This new polymorphism can be detected with three different restriction enzymes: Hind III, Sac I, a~d Eco RV. Only C57BL/6 and closely related inbred strains displayed this polymorphism (had a different restriction fragment size compared to all other inbred strains tested). Linkage of Ah to the restriction fragment length polymorphism was first determined by comparing the strain distribution pattern of the restriction fragment length polymorphism to. all other strain distribution patterns of polymorphic loci in the BXD (C57BL/6 x. DBA/2) recombinant inbred set. Confirmation of this linkage was achieved by a backcross. Both the·restriction fragment length polymorphism and.Ah were 1 2 found not be linked to the standard genetic markers Hba, Hbb, ~, ~, C-3, and Wv. The strain distribution pattern of another restriction fragment length polymorphism, known to be located on Chromosome 12, was compared to the strain distribution pattern of the restriction fragment length polymorphism described iri this investigation. The 24 out of 24 match proves that 'the Ah locus is on -mouse ·chromosome 12.
    Affiliation
    Department of Cell and Molecular Biology
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    Theses and Dissertations

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