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A study to determine genetic susceptibility to tuberculosis / Kathleen Anne Meehan.
Author(s)
Meehan, Kathleen Anne
Date Issued
1992
Type
Thesis
Publisher
Cape Technikon
Abstract
Studies that document the higher incidence of tuberculosis as well as the variable efficacy
of the BCG vaccine in Black, compared to White, populations have alluded to resistance
or susceptibility to tuberculosis being genetically controlled.The HIA system has been associated with many diseases involving an immune aetiology.
It has been shown that T cell receptor genes have limited restriction fragment length
polymorphisrns, serving to create a variation in the repertoire of expressed T cell receptor
genes. These repertoire differences may play a fundamental role in disease susceptibility.A study was therefore undertaken to establish whether linkage exists between the HIA
system or the T cell receptor genes and a putative susceptibility gene for tuberculosis.Polymorphisrns of these genetic markers were examined in three Cape Coloured
multiplex families, affected individuals having culture-positive pulmonary tuberculosis.HLA haplotypes were derived from serological typing of peripheral leucocytes from each
individual. B-Iymphoblastoid cell lines were established from each family member. DNA
was then extracted and digested with a variety of restriction endonucleases. After gel
electrophoresis and Southern blotting, the DNA fragments were probed with a panel of T
cell receptor cDNA probes, revealing the allelic polymorphisms.Linkage analysis was done using the Liped computer programme and Lad scores were
determined for each marker locus using various genetic models. Haplotypes were also
established for the T cell receptor genes and used in the linkage analysis.Although most of the Lad scores fell within the indeterminate range, a cumulative Lod
score of 1.79 was obtained from the allele generated by the EcoRV/a2 enzyme/probe
combination under a recessive model with 50% penetrance. This represents odds of about
52: 1 in favour of linkage between the T cell receptor a gene and a putative susceptibility
gene to tuberculosis.
of the BCG vaccine in Black, compared to White, populations have alluded to resistance
or susceptibility to tuberculosis being genetically controlled.The HIA system has been associated with many diseases involving an immune aetiology.
It has been shown that T cell receptor genes have limited restriction fragment length
polymorphisrns, serving to create a variation in the repertoire of expressed T cell receptor
genes. These repertoire differences may play a fundamental role in disease susceptibility.A study was therefore undertaken to establish whether linkage exists between the HIA
system or the T cell receptor genes and a putative susceptibility gene for tuberculosis.Polymorphisrns of these genetic markers were examined in three Cape Coloured
multiplex families, affected individuals having culture-positive pulmonary tuberculosis.HLA haplotypes were derived from serological typing of peripheral leucocytes from each
individual. B-Iymphoblastoid cell lines were established from each family member. DNA
was then extracted and digested with a variety of restriction endonucleases. After gel
electrophoresis and Southern blotting, the DNA fragments were probed with a panel of T
cell receptor cDNA probes, revealing the allelic polymorphisms.Linkage analysis was done using the Liped computer programme and Lad scores were
determined for each marker locus using various genetic models. Haplotypes were also
established for the T cell receptor genes and used in the linkage analysis.Although most of the Lad scores fell within the indeterminate range, a cumulative Lod
score of 1.79 was obtained from the allele generated by the EcoRV/a2 enzyme/probe
combination under a recessive model with 50% penetrance. This represents odds of about
52: 1 in favour of linkage between the T cell receptor a gene and a putative susceptibility
gene to tuberculosis.
Additional information
Thesis (Masters Diploma (Medical Technology))-- Cape Peninsula University of Technology, 1992
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