Manda Rossouw | PubMed Health

PubMed2003

Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene.

Interferon gamma is believed to be crucial for host defence against many infections. To test the hypothesis that a polymorphism in the gene for interferon gamma (IFNG) is associated with susceptibility to tuberculosis, we did two independent investigations. In a case-control study of 313 tuberculosis cases, we noted a significant association between a polymorphism (+874A-->T) in IFNG and tuberculosis in a South African population (p=0.0055). This finding was replicated in a family-based study, in which the transmission disequilibrium test was used in 131 families (p=0.005). The transcription factor NFkappaB binds preferentially to the +874T allele, which is over-represented in controls. This preferential binding suggests that genetically determined variability in interferon gamma and expression might be important for the development of tuberculosis.

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PubMed2002

Accurate microsatellite typing and inter-study comparison: pitfalls and solutions using interferon-gamma (IFNG) and natural resistance-associated macrophage protein 2 (NRAMP2) genes as examples.

Microsatellite typing is frequently used in disease diagnosis and in genetic association studies. Inter-study consistency and comparability is essential in both applications. In this study, we show that the interlaboratory comparison of microsatellite sizes is often discrepant and misleading. This is a matter of great concern in the recent literature. However, accurate allele designation is easily attainable by the simple procedures we report, which are applicable to all gel-based genotyping methods. These involve: 1) the creation of dedicated standards for a specific microsatellite by PCR-amplifying representative alleles to generate an allelic ladder with comparable electrophoretic characteristics; 2) including both internal and external standards during electrophoresis to facilitate alignment. In addition, we recommend procedures that will improve inter-study comparability of all microsatellite analyses regardless of genotyping method. These involve: 1) cloning and sequencing representative microsatellite alleles to obtain accurate size designation; 2) sharing alleles of known sequence between laboratories to use as standards. We report on the typing of natural resistance-associated macrophage protein (NRAMP2) and interferon-y (IFNG) gene microsatellites as examples, the latter of which is crucial to many pathogenic processes. We describe in detail the varying allele sizes obtained by different methods, which prevent meaningful inter-study comparisons.

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