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    Recombination and genetic polymorphism at the mouse alpha-globin locus

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    Authors
    Lewis, Jill B
    Issue Date
    1988-12-08
    URI

    http://hdl.handle.net/10675.2/622466
    
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    Abstract
    Unusual genetic phenomena are often responsible for dramatic evolutionary changes at many mammalian loci. Among the possible genetic mechanisms involved in these changes are point mutation, gene-conversion, and homologous or nonhomologous recombination. Rarely can such evolutionarily significant events be studied as recent occurrences in mammalian systems. In most case.s it can only be postulated that such events occurred ·in the distant past. In the case analyzed in this research, however, the genetic rearrangement has occurred within the last fifteen years since the origination of a certa~n inbred mouse strain known as AKXL-7. The AKXL-7 recombinant inbred strain is the product of inbred parental strains AKR and C57L. AKR.has the Hba "f" genetic type which specifies only alpha-globin chain 5. C57L has the Hba "a" genetic type that specifies only alpha-globin chain 1. Chains 1 and 5 are identical except for a gly --> ala substitution at position 78. Although one would predict that any recombinant inbred strain resulting from thes,e parents would be homozygous for one of these two alpha-globin types, this is not the case for the AKXL-7 strain. These mice express both alpha-globin chains, with chain 1 present in greater amounts than chain 5. The type of genetic reassortment that has occurred has been ascertained through the use of DNA probes to flanking regions of the two non-allelic or "tandem" alpha-globin 1 genes. Southern blot analysis has revealed that the left and right AKXL-7 alphaglobin gene flanking regions are homologous to regions from different parents. This result indicates that the novel AKXL-7 genotype is the result of a reciprocal recombination event. Further analysis using an intergenic region probe narrowed the region of crossover to approximately 5.2 kb. Using the most distal flanking region probes, chromosome walking was performed to recover probes useful for characterization of three different induced mouse alphathalassemia mutations. Results indicate that in all three cases the deletion spans. at least 45 kb, including both alphaglobin genes and the-embryonic alpha-like x gene.
    Affiliation
    Department of Cell and Molecular Biology
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