Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene

The most common mycobacterial disease in humans is tuberculosis, and there is evidence for genetic factors in susceptibility to tuberculosis. In the mouse, the Bcg gene controls macrophage priming for activation and is a major gene for susceptibility to infection with mycobacteria. A candidate gene...

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Bibliographic Details
Published in:American journal of human genetics 1995-04, Vol.56 (4), p.845-853
Main Authors: JING LIU, FUJIWARA, T. M, SCHURR, E, BUU, N. T, SANCHEZ, F. O, CELLIER, M, PARADIS, A. J, FRAPPIER, D, SKAMENE, E, GROS, P, MORGAN, K
Format: Article
Language:English
Subjects:
Alleles
amino acid sequence
Animal bacterial diseases
Animals
Bacterial diseases
Base Sequence
Biological and medical sciences
Carrier Proteins - genetics
Cation Transport Proteins
chromosome 2
Chromosome Mapping
Genetic Variation
Humans
Hybrid Cells
Immunity, Innate
Infectious diseases
Iron-Binding Proteins
macrophages
man
Medical sciences
Membrane Proteins - genetics
Mice
Molecular Sequence Data
mutation
Mycobacterium tuberculosis
natural resistance-associated macrophage protein
NRAMP1 gene
nucleotide sequence
Original
Polymorphism, Genetic
prediction
resistance
tuberculosis
Tuberculosis - genetics
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Summary:The most common mycobacterial disease in humans is tuberculosis, and there is evidence for genetic factors in susceptibility to tuberculosis. In the mouse, the Bcg gene controls macrophage priming for activation and is a major gene for susceptibility to infection with mycobacteria. A candidate gene for Bcg was identified by positional cloning and was designated "natural resistance-associated macrophage protein gene" (Nramp1), and the human homologue (NRAMP1) has recently been cloned. Here we report on (1) the physical mapping of NRAMP1 close to VIL in chromosome region 2q35 by PCR analysis of somatic cell hybrids and YAC cloning and (2) the identification of nine sequence variants in NRAMP1. Of the four variants in the coding region, there were two missense mutations and two silent substitutions. The missense mutations were a conservative alanine-to-valine substitution at codon 318 in exon 9 and an aspartic acid-to-asparagine substitution at codon 543 in the predicted cytoplasmic tail of the NRAMP1 protein. A microsatellite was located in the immediate 5' region of the gene, three variants were in introns, and one variant was located in the 3' UTR. The allele frequencies of each of the nine variants were determined in DNA samples of 60 Caucasians and 20 Asians. In addition, we have physically linked two highly polymorphic microsatellite markers, D2S104 and D2S173, to NRAMP1 on a 1.5-Mb YAC contig. These molecular markers will be useful to assess the role of NRAMP1 is susceptibility to tuberculosis and other macrophage-mediated diseases.
ISSN:0002-9297
1537-6605