Abstract
The human major histocompatibility complex (MHC) contains a variety of genes, many of which are highly polymorphic and of immunological importance. A database of MHC extended haplotypes was used to integrate experimental, cell line, and population data. Three alleles of the human TNF-beta (lymphotoxin-alpha) gene were identified, named TNFB *1SL, TNFB *2LL, and TNFB *1LS, each representing a different lineage in the evolution of TNF region haplotypes. Lower variability in the length of the associated microsatellite alleles indicates that *1SL characterizes the youngest of the three haplotype lineages. Microsatellite haplotypes in the two older lineages show evidence for a coevolution of alleles through concerted expansions. Genetic predispositions to high and low TNF-alpha (cachectin) responses seem to have evolved independently in more than one lineage. The literature data suggest different, or even opposite, associations concerning the regulation of TNF-alpha in macrophages and lymphoid cells. Microsatellite ud may be the most informative marker for studies of the associations of individual TNF region markers with secretion levels, immunity, and disease.
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Received: 10 December 1996 / Revised: 21 May 1997
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Weissensteiner, T., Lanchbury, J. TNFB polymorphisms characterize three lineages of TNF region microsatellite haplotypes. Immunogenetics 47, 6–16 (1997). https://doi.org/10.1007/s002510050320
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DOI: https://doi.org/10.1007/s002510050320