Alternative titles; symbols
HGNC Approved Gene Symbol: SLC11A1
Cytogenetic location: 2q35 Genomic coordinates (GRCh38): 2:218,382,273-218,396,894 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 2q35 | {Buruli ulcer, susceptibility to} | 610446 | 3 | |
| {Mycobacterium tuberculosis, susceptibility to infection by} | 607948 | 3 |
SLC11A1 is a host resistance factor that controls susceptibility to the intracellular pathogens Salmonella, Mycobacteria, and Leishmania. SLC11A1 transports Fe(2+), Mn(2+), and Co(2+) out of phagosomes, thereby depriving vacuolar pathogens of essential micronutrients. In addition, SLC11A1 modulates phagosome maturation, proinflammatory cytokines and activation of innate lymphocytes, generation of nitric oxide, reactive oxygen species, and lipocalin-2 (LCN2; 600181), and iron homeostasis (summary by Cunrath and Bumann, 2019).
Natural resistance to infection with unrelated intracellular parasites such as Mycobacteria, Salmonella, and Leishmania is controlled in the mouse by a single gene on chromosome 1, designated Bcg, Ity, or Lsh. In the region of the Bcg gene on mouse chromosome 1, Vidal et al. (1993) identified several candidate transcription units. One of the candidate genes, designated Nramp for natural resistance-associated macrophage protein, was found to encode a novel macrophage-specific polypeptide with predicted features characteristic of an integral membrane protein. Nucleotide sequence analyses of the Nramp cDNA showed that in 27 inbred mouse strains of either resistant or susceptible phenotypes, susceptibility was associated with a nonconservative glycine-to-aspartic acid amino acid substitution within the second transmembrane domain of the protein (Malo et al., 1994).
Cellier et al. (1994) cloned and characterized cDNA clones corresponding to the human NRAMP gene. Sequence analyses indicated that the human polypeptide is a 550-amino acid membrane protein with 10 to 12 putative transmembrane domains, 2 N-linked glycosylation sites, and an evolutionarily conserved consensus transport motif.
By screening a human monocyte cDNA library, Kishi (1994) isolated the cDNA for human NRAMP. The 2,245-bp cDNA codes for a protein of 483 amino acid residues with a molecular mass of 52.8 kD. The deduced amino acid sequence is 89% homologous with that of mouse. Southern blot analysis indicated that the NRAMP gene is present in single dose in the human genome. Northern blot analysis demonstrated a single species of mRNA of approximately 2.5 kb.
Blackwell et al. (1995) demonstrated that the human NRAMP gene encodes a 550-amino acid protein showing 85% identity (92% similarity) with mouse Nramp. No mutations comparable to the mouse susceptibility mutation were found.
Cellier et al. (1995) identified Nramp homologs from Drosophila melanogaster, Oryza sativa (rice), and Saccharomyces cerevisiae. Optimal alignment of protein sequences required insertion of very few gaps and revealed remarkable sequence identity of 55%, 40%, and 28%, respectively, with the mammalian proteins (73%, 58%, and 46% similarity), as well as a common predicted transmembrane topology. The NRAMP family is defined by a highly conserved hydrophobic core encoding 10 transmembrane segments. This and other characteristics suggested to the authors that NRAMP polypeptides form part of a group of transporters or channels that act on as yet unidentified substrates.
By analysis of a bovine cDNA homolog of murine Nramp1, Feng et al. (1996) predicted a 548-amino acid protein with hydrophobic domains, an N-terminal SH3-binding domain, and a conserved consensus transport motif. Northern blotting indicated that bovine NRAMP1 is expressed primarily in macrophages and tissues of the reticuloendothelial system.
Hu et al. (1997) found that in the chicken, as in mice, the NRAMP1 gene is involved in natural resistance to infection with Salmonella typhimurium.
Canonne-Hergaux et al. (2002) generated a polyclonal antibody against human NRAMP1 protein and used the reagent to study cellular and subcellular localization of the protein in human neutrophils. The findings suggested the possible role of NRAMP1 in neutrophil function and provided a link with the association of NRAMP1 with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis (Shaw et al., 1996) and Crohn disease.
Cellier et al. (1994) determined that the NRAMP gene contains at least 15 exons and an alternatively spliced exon encoded by an Alu element present within intron 4.
Blackwell et al. (1995) demonstrated that the human NRAMP gene spans 12 kb and has 15 exons. The transcriptional initiation site mapped 148 bp 5-prime of the translation initiation codon.
Marquet et al. (2000) reported the nucleotide sequence of 32,198 bp of genomic DNA overlapping NRAMP1 on 2q35. They found that the NRAMP1 gene spans 13,604 bp. They also identified a gene, which they called nuclear LIM interactor-interacting factor (NLIIF; 605323), in the immediate vicinity of NRAMP1.
By use of sequence-specific oligonucleotide primers derived from the human NRAMP cDNA, Cellier et al. (1994) obtained a specific NRAMP PCR amplification product from several genomic YAC clones containing VIL1 (193040), the gene encoding villin, which maps to 2q35-q36. Additional physical mapping of these YAC clones indicated that NRAMP and VIL are located on a genomic fragment of maximum size 220 kb. White et al. (1994) demonstrated that the IL8RA (146929) and IL8RB (146928) genes lie in the interval between NRAMP and VIL1.
Blackwell et al. (1995) found that a possible enhancer element in the NRAMP gene was polymorphic and used it for linkage analysis to map the NRAMP gene to 2q35. Liu et al. (1995) likewise mapped NRAMP1 to 2q35 by PCR analysis of somatic cell hybrids and YAC cloning.
Feng et al. (1996) mapped the bovine Nramp gene to chromosome 2 within syntenic loci conserved on human 2q and mouse chromosome 1.
Liu et al. (1995) identified 9 sequence variants in the NRAMP gene. Four variants were in the coding region of the gene; 2 were missense mutations and 2 were silent nucleotide substitutions. The missense mutations were in exon 9 and in the predicted cytoplasmic tail of the NRAMP1 protein. A microsatellite was located in the immediate 5-prime region of the gene, 3 variants were in introns, and 1 variant was located in the 3-prime UTR. The allele frequencies in each of the 9 variants were determined in DNA samples from 60 Caucasians and 20 Asians. In addition, Liu et al. (1995) physically linked 2 highly polymorphic microsatellite markers, D2S104 and D2S173, to NRAMP1 on a 1.5-Mb YAC contig. They commented that these molecular markers should be useful in assessing the role of NRAMP1 in susceptibility to tuberculosis and other macrophage-mediated diseases.
Newport et al. (1995) excluded a mutation in NRAMP as the cause of familial disseminated atypical mycobacterial infection (see 209950) in a Maltese kindred.
In a case-control study of tuberculosis in the Gambia, West Africa, Bellamy et al. (1998) typed polymorphisms in NRAMP1 in 410 adults (mean age 34.7 years) with smear-positive pulmonary tuberculosis and 417 ethnically matched, healthy controls. Patients with human immunodeficiency virus infection were excluded. Four NRAMP1 polymorphisms were each significantly associated with tuberculosis. Subjects who were heterozygous for 2 NRAMP1 polymorphisms in intron 4 and the 3-prime untranslated region of the gene were particularly overrepresented among those with tuberculosis, as compared with those with the most common NRAMP1 genotype (odds ratio, 4.07).
Cervino et al. (2000) analyzed 4 families from Guinea-Conakry to test for association between NRAMP1 polymorphisms and tuberculosis. A single base change in intron 4 was significantly associated (p = 0.036) with tuberculosis. Thus, the previously reported association between this polymorphism and tuberculosis in a population-based study of West Africans was confirmed.
By sib-pair linkage analyses of 168 members of twenty 2-generation multiplex leprosy (approximately 50% multibacillary; see 246300) families of Vietnamese and Chinese descent, Abel et al. (1998) determined that there was a significant (p less than 0.02) nonrandom segregation of an 'extended' chromosome 2 haplotype. The extended haplotype included NRAMP1, a RFLP within the TNP1 gene (190231), and 3 highly polymorphic chromosome 2 D-segment markers (D2S1471, D2S173, and D2S104). Analysis of an intragenic haplotype of 6 diallelic NRAMP1 polymorphisms showed that the association approached statistical significance (p less than 0.06). Both the extended and the intragenic haplotype sharing were stronger and statistically significant among the 16 Vietnamese families. Monte Carlo simulations suggested that leprosy susceptibility might be associated with NRAMP1 and additional genetic loci.
The Mitsuda test, unlike the 3-day tuberculin test for diagnosis of tuberculosis infection, measures the response 3 or 4 weeks after the intradermal injection of heat-killed M. leprae (or lepromin) and has a high prognostic value for susceptibility (when negative) or resistance (when positive) to the multibacillary or lepromatous form of leprosy. By linkage analysis between the NRAMP1 genome region and the extent of the Mitsuda skin reaction in 118 sibs (half with leprosy) of families with leprosy in Vietnam, Alcais et al. (2000) observed significant linkage between NRAMP1 and the Mitsuda reaction either as a quantitative or a categorical trait, independent of leprosy status.
Searle and Blackwell (1999) reported a polymorphism in the promoter of NRAMP1 encoding a Z-DNA-forming dinucleotide repeat with 4 alleles. Alleles 1 and 4 had gene frequencies around 0.001; alleles 2 and 3 occurred at gene frequencies of approximately 0.20 to 0.25 and approximately 0.75 to 0.80, respectively. Luciferase reporter gene constructs were used to show that the 4 alleles differed in their ability to drive gene expression. In the absence of exogenous stimuli, alleles 1, 2, and 4 were poor promoters, while allele 3 was found to drive high expression. All 4 alleles showed a similar percentage enhancement of reporter gene expression in the presence of interferon-gamma, consistent with multiple interferon-gamma response elements both 5-prime and 3-prime of the Z-DNA-forming repeat. The addition of bacterial lipopolysaccharide (LPS) had no effect on alleles 1 and 4 but caused significant reduction in expression driven by allele 2 and enhanced expression driven by allele 3. Searle and Blackwell (1999) suggested that the juxtaposition of LPS-related response elements might be differentially affected by the 2 commonly occurring alleles. Searle and Blackwell (1999) concluded that their results were consistent with the hypothesis that chronic hyperactivation of macrophages associated with allele 3 was functionally linked to autoimmune disease susceptibility, while the poor level of NRAMP1 expression promoted by allele 2 contributed to infectious disease susceptibility. Conversely, they found that allele 3 protects against infectious disease and allele 2 against autoimmune disease. They speculated that alleles that are detrimental in relation to autoimmune disease susceptibility may be maintained in the population because they improve survival to reproductive age following infectious disease challenge.
Graham et al. (2000) analyzed the microsatellite repeat region in the promoter region described by Blackwell et al. (1995) and identified a further 2 alleles, which they named alleles 5 and 6. They noted that using some methods of analysis, allele 5 could be mistaken for the previously described allele 3. Graham et al. (2000) found that allele 5 was significantly more common in patients with primary biliary cirrhosis (PBC; 109720) than in normal controls, patients with alcoholic liver disease, or patients with hepatitis C.
An epidemic of tuberculosis occurred in a community of aboriginal Canadians during the period of 1987 to 1989. Greenwood et al. (2000) collected genetic and epidemiologic data on an extended family from this community, and assessed evidence for linkage to NRAMP1. Individuals were grouped into risk (liability) classes based on vaccination, age, previous disease, and tuberculin skin-test results. Under the assumption of a dominant mode of inheritance and a relative risk of 10, which is associated with the high-risk genotypes, Greenwood et al. (2000) observed a maximum lod score of 3.81 for linkage between a tuberculosis susceptibility locus and D2S424, which is located just distal to NRAMP1, in 2q35. Significant linkage was also observed between a tuberculosis susceptibility locus and a haplotype of 10 NRAMP1 intragenic variants. No linkage to the major histocompatibility complex region on 6p was observed, despite distortion of transmission from one member of the oldest couple to their affected offspring.
Mohamed et al. (2004) examined polymorphisms in the SLC11A1 gene in 59 multicase families with visceral leishmaniasis, which is also known as kala-azar (608207), from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis showed significant linkage across SLC11A1 (Z(lr) scores, 2.38-2.55; p between 0.008 and 0.012). The extended transmission disequilibrium test showed biased transmission of alleles at 5-prime polymorphisms in the promoter region (p = 0.0145), exon 3 (p = 0.0037), and intron 4 (p = 0.0049), and haplotypes formed by them (p = 0.0089). Stepwise logistic regression analysis using a case/pseudo-control data set derived from the 59 families suggested that all of the association with visceral leishmaniasis was contributed by the 469+14G-C polymorphism in intron 4.
Using a family-based control design to study 184 ethnically diverse families from the Houston, Texas, area with at least 1 child affected with pediatric tuberculosis disease, Malik et al. (2005) identified 4 NRAMP1 allelic variants associated with pediatric tuberculosis disease. The most significant association was found with the common C allele of the N02 SNP (600266.0001). The association between the C allele of N02 and pediatric tuberculosis disease was stronger in males from simplex rather than multiplex families, suggesting an interplay between genetic control and the intensity of exposure to M. tuberculosis. Malik et al. (2005) proposed that NRAMP1 effects are most pronounced in the absence of prior exposure to mycobacteria. They suggested that NRAMP1 modulates the speed of progression from infection to disease, possibly by antagonizing the blockage of phagosome maturation induced by the pathogen.
In a study of 86 patients with sarcoidosis (see 181000), 85 patients with tuberculosis (TB), and 93 healthy controls, Dubaniewicz et al. (2005) found a significant association between allele 3 of the functional (GT)n repeat polymorphism in the promoter region of the SLC11A1 gene in sarcoidosis patients compared to TB patients and controls (odds ratio = 1.68, p = 0.04; and odds ratio = 1.69, p = 0.03, respectively).
Buruli ulcer (610446) is an infectious disease prevalent in many tropical and subtropical regions caused by infection with Mycobacterium ulcerans. Stienstra et al. (2006) hypothesized that many individuals exposed to Mycobacterium ulcerans never develop Buruli ulcer disease. Since polymorphisms in NRAMP1 are associated with both tuberculosis and leprosy, they conducted a cross-sectional analysis of 182 Buruli ulcer patients in Ghana and 191 healthy neighborhood-matched controls for 3 NRAMP1 polymorphisms. A statistically significant association was found for a G-to-A SNP in exon 15 that leads to a nonconservative asp543-to-asn substitution (D543N; 600266.0002). A similar association with D543N had been found in tuberculosis patients in the Gambia (Bellamy et al., 1998). No Ghanaians were homozygous for the A allele of this SNP. Stienstra et al. (2006) determined that the population attributable risk of D543N is 13%, and they proposed that other genes are likely to be involved in Buruli ulcer susceptibility.
Wicker et al. (2004) determined that the Slc11a1 gene is the strongest candidate among the 42 genes in the Idd5.2 region, 1 of more than 20 type 1 diabetes loci that have been implicated in the nonobese diabetic (NOD) mouse model. A naturally occurring mutation in the protective Idd5.2 haplotype results in loss of function in the Slc11a1 protein. By RNA interference, Kissler et al. (2006) suppressed the Slc11a1 gene in NOD mice and found that silencing reduced the frequency of type 1 diabetes (T1D; 222100), mimicking the protective Idd5.2 region. The results demonstrated a role for Slc11a1 in modifying susceptibility to T1D. In NOD mice, protection from autoimmunity afforded by loss of Slc11a1 correlated with increased susceptibility to infection, as previously proposed in humans (Searle and Blackwell, 1999), where some reports have also suggested an association between Slc11a1 expression and diabetes (Nishino et al., 2005) and rheumatoid arthritis (Shaw et al., 1996).
Soe-Lin et al. (2009) presented evidence that Nramp1 participates in macrophage recycling of iron acquired from the phagocytosis of senescent erythrocytes. Nramp1-null mice had higher splenic iron content, increased transferrin saturation, and lower hepcidin (HAMP; 606464) mRNA compared to wildtype mice. The results were consistent with inefficient recycling of erythrophagocytosed iron and retention of iron within reticuloendothelial cells. The paradoxical increase in transferrin saturation was due to a compensatory increase in dietary iron absorption. Nramp1-null mice also showed impaired recovery from induced acute and chronic hemolytic anemia compared to wildtype mice. Under the stress conditions, Nramp1-null mice showed significantly decreased transferrin saturation and increased levels of nonheme iron in the liver and spleen compared to wildtype mice under the same conditions, indicating an inability of Nramp1-null mice to depend on stored iron for erythropoietic needs. Splenic macrophages from these mice showed increased iron deposits. The hypothesis that iron could not be appropriately released from macrophages in Nramp1-null mice was confirmed using radiolabeled iron.
Cunrath and Bumann (2019) compared Salmonella infection of coisogenic mice with different Slc11a1 alleles. They found that Slc11a1 reduced Salmonella replication and triggered upregulation of uptake systems for divalent metal cations, but not other stress responses. Slc11a1 modestly diminished iron availability and acutely restricted Salmonella access to magnesium. Growth of Salmonella cells in the presence of Slc11a1 was highly heterogeneous and inversely correlated with expression of the essential Salmonella magnesium transporter gene mgtB. Cunrath and Bumann (2019) observed superimposable single-cell patterns in mice lacking Slc11a1 when they restricted Salmonella access to magnesium by impairing its uptake. The authors concluded that deprivation of magnesium is the main resistance mechanism of SLC11A1 against Salmonella.
Using a family-based control design to study 184 ethnically diverse families from the Houston, Texas, area with at least 1 child affected with pediatric tuberculosis disease (see 607948), Malik et al. (2005) identified 4 NRAMP1 allelic variants associated with pediatric tuberculosis disease. The most significant association was found with the common C allele of the N02 SNP (274C-T in exon 3). The association between the N02 C allele and pediatric tuberculosis disease was stronger in males from simplex rather than multiplex families, suggesting an interplay between genetic control and the intensity of exposure to M. tuberculosis. Malik et al. (2005) concluded that the N02 C allele promotes rapid progression from infection to disease.
Stienstra et al. (2006) studied 182 patients with Buruli ulcer disease (610446) and 191 healthy subjects in Ghana and found that a G-to-A SNP in exon 15 of the SLC11A1 gene, resulting in an asp543-to-asn (D543N) substitution, was significantly associated with susceptibility to disease.
Abel, L., Sanchez, F. O., Oberti, J., Thuc, N. V., Hoa, L. V., Lap, V. D., Skamene, E., Lagrange, P. H., Schurr, E. Susceptibility to leprosy is linked to the human NRAMP1 gene. J. Infect. Dis. 177: 133-145, 1998. [PubMed: 9419180] [Full Text: https://doi.org/10.1086/513830]
Alcais, A., Sanchez, F. O., Thuc, N. V., Lap, V. D., Oberti, J., Lagrange, P. H., Schurr, E., Abel, L. Granulomatous reaction to intradermal injection of lepromin (Mitsuda reaction) is linked to the human NRAMP1 gene in Vietnamese leprosy sibships. J. Infect. Dis. 181: 302-308, 2000. [PubMed: 10608779] [Full Text: https://doi.org/10.1086/315174]
Bellamy, R., Ruwende, C., Corrah, T., McAdam, K. P. W. J., Whittle, H. C., Hill, A. V. S. Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans. New Eng. J. Med. 338: 640-644, 1998. [PubMed: 9486992] [Full Text: https://doi.org/10.1056/NEJM199803053381002]
Blackwell, J. M., Barton, C. H., White, J. K., Searle, S., Baker, A.-M., Williams, H., Shaw, M.-A. Genomic organization and sequence of the human NRAMP gene: identification and mapping of a promoter region polymorphism. Molec. Med. 1: 194-205, 1995. [PubMed: 8529098]
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Cellier, M., Govoni, G., Vidal, S., Kwan, T., Groulx, N., Liu, J., Sanchez, F., Skamene, E., Schurr, E., Gros, P. Human natural resistance-associated macrophage protein: cDNA cloning, chromosomal mapping, genomic organization, and tissue-specific expression. J. Exp. Med. 180: 1741-1752, 1994. [PubMed: 7964458] [Full Text: https://doi.org/10.1084/jem.180.5.1741]
Cellier, M., Prive, G., Belouchi, A., Kwan, T., Rodrigues, V., Chia, W., Gros, P. Nramp defines a family of membrane proteins. Proc. Nat. Acad. Sci. 92: 10089-10093, 1995. [PubMed: 7479731] [Full Text: https://doi.org/10.1073/pnas.92.22.10089]
Cervino, A. C. L., Lakiss, S., Sow, O., Hill, A. V. S. Allelic association between the NRAMP1 gene and susceptibility to tuberculosis in Guinea-Conakry. Ann. Hum. Genet. 64: 507-512, 2000. [PubMed: 11281214] [Full Text: https://doi.org/10.1046/j.1469-1809.2000.6460507.x]
Cunrath, O., Bumann, D. Host resistance factor SLC11A1 restricts Salmonella growth through magnesium deprivation. Science 366: 995-999, 2019. [PubMed: 31753999] [Full Text: https://doi.org/10.1126/science.aax7898]
Dubaniewicz, A., Jamieson, S. E., Dubaniewicz-Wybieralska, M., Fakiola, M., Miller, E. N., Blackwell, J. M. Association between SLC11A1 (formerly NRAMP1) and the risk of sarcoidosis in Poland. Europ. J. Hum. Genet. 13: 829-834, 2005. [PubMed: 15702130] [Full Text: https://doi.org/10.1038/sj.ejhg.5201370]
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Graham, A. M., Dollinger, M. M., Howie, S. E. M., Harrison, D. J. Identification of novel alleles at a polymorphic microsatellite repeat region in the human NRAMP1 gene promoter: analysis of allele frequencies in primary biliary cirrhosis. J. Med. Genet. 37: 150-152, 2000. [PubMed: 10712108] [Full Text: https://doi.org/10.1136/jmg.37.2.150]
Greenwood, C. M. T., Fujiwara, T. M., Boothroyd, L. J., Miller, M. A., Frappier, D., Fanning, E. A., Schurr, E., Morgan, K. Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family. Am. J. Hum. Genet. 67: 405-416, 2000. [PubMed: 10882571] [Full Text: https://doi.org/10.1086/303012]
Hu, J., Bumstead, N., Barrow, P., Sebastiani, G., Olien, L., Morgan, K., Malo, D. Resistance to Salmonellosis in the chicken is linked to NRAMP1 and TNC. Genome Res. 7: 693-704, 1997. [PubMed: 9253598] [Full Text: https://doi.org/10.1101/gr.7.7.693]
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Newport, M., Levin, M., Blackwell, J., Shaw, M.-A., Williamson, R., Huxley, C. Evidence for exclusion of a mutation in NRAMP as the cause of familial disseminated atypical mycobacterial infection in a Maltese kindred. J. Med. Genet. 32: 904-906, 1995. [PubMed: 8592339] [Full Text: https://doi.org/10.1136/jmg.32.11.904]
Nishino, M., Ikegami, H., Fujisawa, T., Kawaguchi, Y., Kawabata, Y., Shintani, M., Ono, M., Ogihara, T. Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis. Metab. Clin. Exp. 54: 628-633, 2005. [PubMed: 15877293] [Full Text: https://doi.org/10.1016/j.metabol.2004.12.006]
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Shaw, M.-A., Clayton, D., Atkinson, S. E., Williams, H., Miller, N., Sibthorpe, D., Blackwell, J. M. Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35. J. Med. Genet. 33: 672-677, 1996. [PubMed: 8863160] [Full Text: https://doi.org/10.1136/jmg.33.8.672]
Soe-Lin, S., Apte, S. S., Andriopoulos, B., Jr., Andrews, M. C., Schranzhofer, M., Kahawita, T., Garcia-Santos, D., Ponka, P. Nramp1 promotes efficient macrophage recycling of iron following erythrophagocytosis in vivo. Proc. Nat. Acad. Sci. 106: 5960-5965, 2009. [PubMed: 19321419] [Full Text: https://doi.org/10.1073/pnas.0900808106]
Stienstra, Y., van der Werf, T. S., Oosterom, E., Nolte, I. M., van der Graaf, W. T. A., Etuaful, S., Raghunathan, P. L., Whitney, E. A. S., Ampadu, E. O., Asamoa, K., Klutse, E. Y., te Meerman, G. J., Tappero, J. W., Ashford, D. A., van der Steege, G. Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism. Genes Immun. 7: 185-189, 2006. [PubMed: 16395392] [Full Text: https://doi.org/10.1038/sj.gene.6364281]
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Wicker, L. S., Chamberlain, G., Hunter, K., Rainbow, D., Howlett, S., Tiffen, P., Clark, J., Gonzalez-Munoz, A., Cumiskey, A. M., Rosa, R. L., Howson, J. M., Smink, L. J., Kingsnorth, A., Lyons, P. A., Gregory, S., Rogers, J., Todd, J. A., Peterson, L. B. Fine mapping, gene content, comparative sequencing, and expression analyses support Ctla-4 and Nramp-1 as candidates for Idd5.1 and Idd5.2 in the nonobese diabetic mouse. J. Immun. 173: 164-173, 2004. [PubMed: 15210771] [Full Text: https://doi.org/10.4049/jimmunol.173.1.164]