Browsing by Author "Franke, Andre"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Exome sequencing identifies a novel MAP3K14 mutation in recessive atypical combined immunodeficiency
    (Frontiers, 2017-11) Schlechter, Nikola; Glanzmann, Brigitte; Hoal, Eileen Garner; Schoeman, Mardelle; Petersen, Britt-Sabina; Franke, Andre; Lau, Yu-Lung; Urban, Michael; Van Helden, Paul David; Esser, Maria Esser; Moller, Marlo; Kinnear, Craig
    ENGLISH ABSTRACT: Primary immunodeficiency disorders (PIDs) render patients vulnerable to infection with a wide range of microorganisms and thus provide good in vivo models for the assessment of immune responses during infectious challenges. Priming of the immune system, especially in infancy, depends on different environmental exposures and medical practices. This may determine the timing and phenotype of clinical appearance of immune deficits as exemplified with early exposure to Bacillus Calmette-Guérin (BCG) vaccination and dissemination in combined immunodeficiencies. Varied phenotype expression poses a challenge to identification of the putative immune deficit. Without the availability of genomic diagnosis and data analysis resources and with limited capacity for functional definition of immune pathways, it is difficult to establish a definitive diagnosis and to decide on appropriate treatment.
  • Thumbnail Image
    Item
    A post-GWAS analysis of predicted regulatory variants and tuberculosis susceptibility
    (Public Library of Science, 2017) Uren, Caitlin; Henn, Brenna M.; Franke, Andre; Wittig, Michael; Van Helden, Paul D.; Hoal, Eileen G.; Moller, Marlo
    Utilizing data from published tuberculosis (TB) genome-wide association studies (GWAS), we use a bioinformatics pipeline to detect all polymorphisms in linkage disequilibrium (LD) with variants previously implicated in TB disease susceptibility. The probability that these variants had a predicted regulatory function was estimated using RegulomeDB and Ensembl's Variant Effect Predictor. Subsequent genotyping of these 133 predicted regulatory polymorphisms was performed in 400 admixed South African TB cases and 366 healthy controls in a population-based case-control association study to fine-map the causal variant. We detected associations between tuberculosis susceptibility and six intronic polymorphisms located in MARCO, IFNGR2, ASHAS2, ACACA, NISCH and TLR10. Our post- GWAS approach demonstrates the feasibility of combining multiple TB GWAS datasets with linkage information to identify regulatory variants associated with this infectious disease.