Mutations in the Human
Mannose-Binding Protein Gene:
Frequencies in Several Population
Groups

Lipscombe, Richard; Beatty, David M.; Ganczakowski, M; Goddard, E.; Jenkins, Trefor; Lau, Y. L.; Spurdle, Amanda B.; Sumiya, M.; Summerfield, John A.; Turner, M. W.

doi:10.1159/000472164

Cited by 82 publications

(58 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The distribution of haplotypes differed by group: as published in previous studies, B and D alleles were common in CA, whereas the C allele was most frequent in the population of African origin (see Figure 6). 10,14 The B allele was strongly linked to an additional SNP in the Population-specific haplotypes; haplotype distribution is shown across the entire locus and with regard to the block-like structure based on r for each of the four populations separately. The 'secretor haplotypes' are only based on their six markers without additional loci (H/L, X/Y, P/Q as well as B, C and D).…”

Section: Ld In Mbl2mentioning

confidence: 98%

“…Prior studies have shown that the B allele is rarely seen in African ancestry, which was confirmed in our study. 10,14,94 As LYPB and HYPD occur with high frequency in non-African populations and share nearly all segregating sites for haplotype determination, we propose that the older 'secretor haplotypes' are LYPA and HYPA. Furthermore, this would date B and D as alleles that arose later.…”

mentioning

confidence: 89%

“…11 Each of the three structural gene polymorphisms in exon 1, known as the B, C and D alleles, interfere with the formation of higher MBL oligomers, leading to alterations in function and circulating levels. [12][13][14][15] Two strongly linked single-nucleotide polymorphisms (SNPs) lie in the proximal promoter (known as L/H and X/Y), as well as an SNP in the 5 0 UTR (known as P/Q); together, these upstream SNPs are linked to the three independent nonsynonymous SNPs (ie, B, C and D) to form the 'secretor haplotypes', which have previously been shown to partially account for alterations in complement activation and decreased circulating levels of MBL. 7,9,10,[16][17][18][19][20] Using the six SNPs above, it is possible to map circulating levels against the seven common 'secretor haplotypes' in at least 85% of subjects.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection

et al. 2004

View full text Add to dashboard Cite

Human mannose-binding protein (MBL) is a component of innate immunity. To capture the common genetic variants of MBL2, we resequenced a 10.0 kb region that includes MBL2 in 102 individuals representing four major US ethnic groups. In all, 87 polymorphic sites were observed, indicating a high level of heterozygosity (total p ¼ 18.3 Â 10 À4 ). Estimates of linkage disequilibrium across MBL2 indicate that it is divided into two blocks, with a probable recombination hot spot in the 3 0 end. Three non-synonymous SNPs in exon 1 of the encoding MBL2 gene and three upstream SNPs form common 'secretor haplotypes' that can predict circulating levels. Common variants have been associated with increased susceptibility to infection and autoimmune diseases. The high frequencies of B, C and D alleles in certain populations suggest a possible selective advantage for heterozygosity. There is limited diversity of haplotype structure; the 'secretor haplotypes' lie on a restricted number of extended haplotypes, which could include additional linked SNPs, which might also have possible functional implications. There is evidence for gene conversion in the region between the two blocks, in the last exon. Our data should form the basis for conducting MBL2 candidate gene association studies using a locus-wide approach. Keywords: mannose-binding lectin; innate immunity; genetic variation; recombination hot spot; gene conversion IntroductionThe human mannose-binding protein (MBL) is an important component of the innate immune system and provides first-line protection against pathogens as an 'ante-antibody'. 1 MBL is a C-type collectin that functions as a pattern-recognition molecule in the immediate response to invading organisms. Carbohydrate structures on the surfaces of microorganisms (bacteria, fungi and parasites) are recognized by MBL, 2-5 which, in turn, lead to opsonization or activation of the lectin pathway of complement via associated mannosebinding lectin serine proteases (MASP2). [6][7][8] Decreased serum levels of MBL have been correlated with an increased risk for infection in both healthy children and immunocompromised individuals. Circulating levels of MBL and functional activity are partially regulated by genetic variation in the MBL2 gene, which encodes MBL. 9,10 The MBL2 gene is located on chromosome 10q11.2-21 and consists of four exons. 11 Each of the three structural gene polymorphisms in exon 1, known as the B, C and D alleles, interfere with the formation of higher MBL oligomers, leading to alterations in function and circulating levels. [12][13][14][15] Two strongly linked single-nucleotide polymorphisms (SNPs) lie in the proximal promoter (known as L/H and X/Y), as well as an SNP in the 5 0 UTR (known as P/Q); together, these upstream SNPs are linked to the three independent nonsynonymous SNPs (ie, B, C and D) to form the 'secretor haplotypes', which have previously been shown to partially account for alterations in complement activation and decreased circulating levels of MBL. 7,9,10,[16][17][18][19][20] Using ...

show abstract

Section: Ld In Mbl2mentioning

confidence: 98%

mentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The mutations leading to the substitution of glycine residues are probably introduced by specific but independent events. The most likely introduction of an analogue mutation in two homologous genes is through 60 Lipscombe et al, 62 Juliger et al, 63 Turner et al 64 and *own unpublished results. NF ¼ Not found.…”

Section: Maintenance Of High Frequencies Of Mbl2 Variant Alleles In Dmentioning

confidence: 99%

Mannose-binding lectin and its genetic variants

et al. 2006

View full text Add to dashboard Cite

Mannose-binding lectin (MBL) is a collagen-like serum protein that mediates activation of the complement system and is of importance for host defence. Common variant alleles situated both in the promoter and structural region of the human MBL gene (MBL2) influence the stability and the serum concentration of the protein. Epidemiological studies have suggested that genetically determined variation in MBL serum concentration influences the susceptibility to and the course of different types of infections, autoimmune, metabolic and cardiovascular diseases, but this is still a subject of debate. The fact that these genetic variations are very frequent indicates a dual role for MBL in host defence. In this survey, we summarize the current molecular understanding of human MBL genetics.

show abstract

“…A similar high prevalence rate has also been found in South Africa (27%). 18 In this context, it is of particular interest to note that in South American populations, low serum MBL concentrations were primarily because of G54D mutation while in East Africa it is because of G57E mutation in combination with relatively high frequency of low-producing promoter haplotypes. 19 Taken together, these data suggest that the MBL G57E mutation is indeed of sub-Saharan African origin and is the most ancient mutation, given its widespread distribution throughout Africa.…”

Section: Mbl Alleles In Sub-saharan Africamentioning

confidence: 99%

Mannose-binding lectin alleles in sub-Saharan Africans and relation with susceptibility to infections

Mombo

Ossari

et al. 2003

Genes Immun

View full text Add to dashboard Cite

Mannose-binding lectin (MBL) plays an important role in the early stages of primary infections and during the decay of maternal antibodies in infants. Various studies have looked at the relation between serum MBL concentrations, MBL gene alterations and susceptibility to infections. We investigated the distribution of variant MBL alleles in 626 unrelated adults from sub-Saharan African countries and looked for a potential relation between these alleles and the incidence, prevalence and death rate of tuberculosis for sub-Saharan Africa. We also evaluated the relation between MBL genotypes and susceptibility to HIV-1 infection in 188 Gabonese adults. We found that (i) the prevalence of the common variant MBL alleles is correlated with the incidence of tuberculosis in sub-Saharan Africa (r ¼ 0.565), (ii) the mutant MBL G57E allele, in either the homozygous or compound heterozygous state, is associated with susceptibility to HIV-1 infection in the Gabonese population (P ¼ 0.019).Our data plus those in the literature suggest that individuals who are homozygous for the mutant MBL alleles display increased susceptibility to infections. Interestingly, we found that individuals who are heterozygous for MBL mutations are much less susceptible to infections than those who are homozygous for the wild-type MBL allele.

show abstract

Mutations in the Human Mannose-Binding Protein Gene: Frequencies in Several Population Groups

Cited by 82 publications

References 19 publications

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection

Mannose-binding lectin and its genetic variants

Mannose-binding lectin alleles in sub-Saharan Africans and relation with susceptibility to infections

Contact Info

Product

Resources

About