• Login
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    QTL mapping of Apc modifiers in an ApcMin/+ mouse model of spontaneous and irradiation-induced intestinal adenomas. 
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • QTL mapping of Apc modifiers in an ApcMin/+ mouse model of spontaneous and irradiation-induced intestinal adenomas.
    •   QMRO Home
    • Queen Mary University of London Theses
    • Theses
    • QTL mapping of Apc modifiers in an ApcMin/+ mouse model of spontaneous and irradiation-induced intestinal adenomas.
    ‌
    ‌

    Browse

    All of QMROCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    ‌
    ‌

    Administrators only

    Login
    ‌
    ‌

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular Authors

    QTL mapping of Apc modifiers in an ApcMin/+ mouse model of spontaneous and irradiation-induced intestinal adenomas.

    View/Open
    E Elahi PhD.pdf (4.259Mb)
    Publisher
    Queen Mary University of London
    Metadata
    Show full item record
    Abstract
    BACKGROUND: Radiation exposure to the abdominal region causes intestinal toxicity and is also capable of inducing colorectal cancers (CRC). Genotype-phenotype studies provide some evidence explaining the variation in familial adenomatous polyposis (FAP) patients caused by modifiers of adenomatous polyposis coli (APC). This study aims to extend our understanding of irradiation-induced modifiers of ApcMin/+ mice and CRC. METHODS: By using a pre-existing backcross between recombinant inbred line of ApcMin/+ mice to the irradiation sensitive inbred BALB/c mouse, we obtained panels of 2Gy-irradiated and sham-irradiated N2 ApcMin/+ mice for genotyping with a genome-wide panel of microsatellites markers. Using the number of adenomas in different intestinal segments to represent polyp multiplicity, we carried out a genome wide quantitative trait loci (QTL) scan followed by statistical epistasis modelling and bioinformatics analysis. RESULTS: We identified five significant QTLs responsible for radiation induced tumour multiplicity in the upper small intestine defined as Mom (Modifier of Min) radiation-induced polyposis (Mrip1-5) on chromosome 2 (LOD 2.8, p = 0.0003), two regions within chromosome 5 (LOD 5.2, p=0.00001, 6.2, p=0.00001) and two regions within chromosome 16 (LOD 4.1, p=4x10-5 and 4.8, p=0.00001). Suggestive QTLs were found for sham-irradiated mice on chromosomes 3, 6 and 13 (LOD 1.7, 1.5 and 2.0 respectively; p,0.005). Two significant QTLs were detected in the 2large intestine on chromosome 2 and 7 (LOD 2.7, p=1.2x10-3 and 2.2, p=1.2x10-3, 12 respectively). Using statistical epistasis modelling and logical selection of target genes though in silico sequence based on BALB/c specific non-synonymous polymorphisms which are predicted deleterious we selected target genes and further eliminated genes by sequencing and mRNA expression. CONCLUSIONS: Our study locates the QTL regions responsible for increased radiation-induced intestinal tumorigenesis in ApcMin/+ mice and identifies candidate genes with predicted functional polymorphisms that are involved in spindle checkpoint and chromosomal stability (Bub1b, Bub1r, and Casc5), Wnt pathway (Tiam1, Rac1), DNA repair (Recc1 and Prkdc) and inflammation (Duox2, Itgb2l and Cxcl5).
    Authors
    Elahi, Eiram.
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/8717
    Collections
    • Theses [3315]
    Copyright statements
    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
    Twitter iconFollow QMUL on Twitter
    Twitter iconFollow QM Research
    Online on twitter
    Facebook iconLike us on Facebook
    • Site Map
    • Privacy and cookies
    • Disclaimer
    • Accessibility
    • Contacts
    • Intranet
    • Current students

    Modern Slavery Statement

    Queen Mary University of London
    Mile End Road
    London E1 4NS
    Tel: +44 (0)20 7882 5555

    © Queen Mary University of London.