Restricted polymorphism of the mannose-binding lectin gene of indigenous Australians

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dc.contributor.authorTurner, M.
dc.contributor.authorDinan, L.
dc.contributor.authorHeatley, S.
dc.contributor.authorJack, D.
dc.contributor.authorBoettcher, B.
dc.contributor.authorLester, S.
dc.contributor.authorMcCluskey, J.
dc.contributor.authorRoberton, D.
dc.date.issued2000
dc.descriptionCopyright © 2000 Oxford University Press
dc.description.abstractMannose-binding lectin (MBL) is an important complement-activating protein of the human innate immune system. Deficiency of MBL is associated with an increased risk of various infections and arises from three structural gene mutations in exon 1 (variants B, C and D) and/or the presence of a low efficiency promoter. The C allele is found in sub-Saharan Africa whereas the B allele is found elsewhere, suggesting that these mutations occurred after the suggested hominid migration out of Africa [100–150 000 years before present (BP)]. Paradoxically, these alleles may have a selective advantage in protection against intracellular pathogens and occur at particularly high frequencies in sub-Saharan Africa (C variant) and South America (B variant). Since hominids reached Australia at least 50 000 years ago, a study of MBL polymorphisms in the indigenous population was of interest. Using heteroduplex technology we found a paucity of MBL structural gene mutations in two population groups from geographically distinct regions. Of 293 individuals tested, 289 were wild-type and four were heterozygous for either the B or D allele. In each individual with an MBL mutation the HLA haplotype profile suggested some Caucasian admixture. We also found a restricted range of MBL promoter haplotypes and the serum MBL levels were higher than those of any other ethnic group studied to date (median 3.07 µg/ml). Our data suggest that the B mutation probably arose between 50 000 and 20 000 BP. Its absence from the founder gene pool of indigenous Australians may also partly explain their vulnerability to intracellular infections such as tuberculosis.
dc.description.statementofresponsibilityMalcolm W. Turner, Leonie Dinan, Susan Heatley, Dominic L. Jack, Barry Boettcher, Susan Lester, James McCluskey and Don Roberton
dc.identifier.citationHuman Molecular Genetics, 2000; 9(10):1481-1486
dc.identifier.doi10.1093/hmg/9.10.1481
dc.identifier.issn0964-6906
dc.identifier.issn1460-2083
dc.identifier.orcidHeatley, S. [0000-0001-7497-6477]
dc.identifier.orcidLester, S. [0000-0003-3013-2701]
dc.identifier.urihttp://hdl.handle.net/2440/7345
dc.language.isoen
dc.publisherOxford Univ Press
dc.source.urihttps://doi.org/10.1093/hmg/9.10.1481
dc.subjectHumans
dc.subjectCarrier Proteins
dc.subjectCollectins
dc.subjectHistocompatibility Testing
dc.subjectEnzyme-Linked Immunosorbent Assay
dc.subjectCohort Studies
dc.subjectHeteroduplex Analysis
dc.subjectGene Frequency
dc.subjectGenotype
dc.subjectHaplotypes
dc.subjectHeterozygote
dc.subjectLinkage Disequilibrium
dc.subjectMutation
dc.subjectPolymorphism, Genetic
dc.subjectAlleles
dc.subjectExons
dc.subjectAustralia
dc.subjectPromoter Regions, Genetic
dc.titleRestricted polymorphism of the mannose-binding lectin gene of indigenous Australians
dc.typeJournal article
pubs.publication-statusPublished

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