Grant Morahan "Gene interactions in type 1 diabetes: a systems genetics approach"

Morahan

Aberrant regulation of immune responses can give rise to autoimmune diseases such as Type 1 Diabetes (T1D). Although many genes have been identified that affect risk of developing T1D, it is not known how they contribute to disease. We applied systems genetics analyses to explore the molecular basis for susceptibility. Over 60 loci have been reported to be associated with T1D. Many of these are defined only by anonymous SNPs: identity of the causative genes, and the molecular bases by which they mediate susceptibility, are not known. To identify these genes, we performed a systematic analysis. First, all known genes in modest linkage disequilibrium with the tag SNP for each locus were examined; we identified common non-synonymous alleles in 259 genes at 39 loci. Next, we examined the effect of SNP genotypes on regulating expression levels of nearby (<2Mb) genes (i.e. cis-regulatory effects typical of promoter/enhancer elements). To do so, we examined gene expression in a total of 442 samples of three different cell types: EBV-transformed B cell lines (resting and after PMA stimulation); and purified CD4+ and CD8+ T cells. We mapped expression quantitative trait loci (eQTL) and found 43 non-HLA loci, typically with P < 1 × 10−7. We tested for trans-regulatory effects (i.e. association with changes in expression of genes located in other chromosomal regions). We found trans-eQTL at 56 non-HLA loci that significantly (P < 1 × 10−8) affected expression of some 2,125 transcripts. Finally, we developed a new approach which allowed us to define distinct genetic subtypes of T1D, and applied this method to other diseases. In summary, our results provide novel insights into the complex genetics of T1D and identified candidate genes for further investigation. Our approach can be applied to other complex genetic diseases for which GWAS data are available.

  • Overview

    The "HZI Colloquium" is a scientific lecture series at the Helmholtz Centre for Infection Research in Braunschweig, organized to host internationally renowned experts from the field of infection research. Invited guest speakers present their current research activities to a scientific audience. The presentation is followed by an open discussion.
    We cordially invite interested scientists to take part in this colloquium.
    The HZI Colloquium takes place on Wednesdays, 5.15 p.m. to 6.30 p.m. in the Forum, X0.13.


    Date: 05.12.2012, 17:15

    Location

    Helmholtz Centre for Infection Research

    Building and room

    Forum, X0.13

    Speaker

    Grant Morahan,
    Western Australian Institute for Medical Research 

    Host

    Klaus Schughart

  • Directions

    How to find us in Braunschweig

    Lage des Helmholtz-Zentrums in der Stadt Braunschweig.

    Address

    Helmholtz Centre for Infection Research

    Inhoffenstraße 7

    38124 Braunschweig

    Car

    From Berlin/Wolfsburg/Helmstedt:

    • A2 till motorway interchange Wolfsburg/Königslutter > A39 direction Kreuz BS-Süd/Wolfenbüttel/Bad Harzburg
    • A39 till motorway interchange Kreuz BS Süd > A395 direction Wolfenbüttel
    • A395 till exit BS-Stöckheim > turn right into Mascheroder Weg
    • after 500m turn left into Inhoffenstraße

    From Celle/Hannover:

    • A2 till motorway interchange Kreuz BS Nord > A391 direction Kreuz BS Süd/Bad Harzburg/Wolfenbüttel
    • A391 motorway interchange Kreuz BS Süd > A395 direction Wolfenbüttel
    • A395 till exit BS-Stöckheim > turn right into Mascheroder Weg
    • after 500m turn left into Inhoffenstraße

    From Kassel/Salzgitter:

    • A7 till motorway interchange Kreuz Salzgitter > A39 direction Berlin/Braunschweig/Salzgitter
    • A39 till motorway interchange Kreuz BS-Süd > A395 direction Wolfenbüttel
    • A395 till exit BS-Stöckheim > turn right into Mascheroder Weg
    • after 500m turn left into Inhoffenstraße

    Train

    Braunschweig Central Station has got two Intercity-Express-Lines, which are connecting Berlin-Braunschweig-Göttingen-Fulda-Frankfurt-Mannheim. 

    Two other Intercity-Lines are in direction to Leipzig, Halle, Magdeburg and Hannover, Bremen, Oldenburg, Bielefeld, Wuppertal and Köln.

    Here you'll get more information about the timetable.

    Bus or Tram

    Bus line 431 or Tram line 1 from central station to stop "Stöckheimer Markt". Turn left into "Mascheroder Weg" and after 500m turn right into "Inhoffenstraße". 

    Futher links:

    Braunschweig traffic corporation

    Electronic time table (EFA)

    Map provided by the city of Braunschweig

    Airplane

    Hannover Airport is about 60 minutes away from Braunschweig (60km). You can hourly take a train in direction of Braunschweig.

    From the International Airport Frankfurt you can reach Braunschweig in 180 minutes by train and it's about 350km away.

    Berlin's Airports Schönefeld and Tegel are 120 minutes away from Braunschweig (230km). A train in direction of Braunschweig leaves every hour.


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