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

Journal Article · Sat Apr 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:70421

Liu, Jing; Fujiwara, T M; Buu, N T; Sanchez, F O; Cellier, M; Paradis, A J; Frappier, D; Skamene, E; Gros, P; Morgan, K ^[1]

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1. McGill Univ., Montreal (Canada)

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 {open_quotes}natural resistance-associated macrophage protein gene{close_quotes} (Nramp1), and the human homologue (NRAMP1) has recently been cloned. Here we report (1) the physical mapping 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 exon9 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{prime} region of the gene, three variants were in introns, and one variant was located in the 3{prime} 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 in susceptibility to tuberculosis and other macrophage-mediated diseases. 40 refs., 3 figs., 2 tabs.

• OSTI ID: 70421
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 4 Vol. 56; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CHROMOSOMES
CONTIGS
DNA HYBRIDIZATION
DNA-CLONING
GENE MUTATIONS
GENES
GENETIC MAPPING
GENETIC VARIABILITY
MACROPHAGES
MICE
MYCOBACTERIUM TUBERCULOSIS
POLYMERASE CHAIN REACTION
SOMATIC CELLS