The human NRAMP1 gene located on Chromosome (Chr) region 2q35 is a candidate gene for increased risk of infection by several intracellular macrophage parasites, including M. tuberculosis and M. leprae. In search for a possible mutational hot spot, we have analyzed a 3.5-kb region 5′ to NRAMP1 that is highly enriched for DNA repeat sequences. The repeat sequences could be grouped into one Mer element and six Alu elements, representing five Alu subfamilies, that had integrated in the same DNA region during successive rounds of Alu retropositional activity. Comparative sequence analysis of the Alu cluster region in humans, chimpanzee (Pan paniscus), and gorilla (Gorilla gorilla) revealed only modest sequence variability and failed to detect any evidence for genomic instability of the highly repetitive DNA region. These results show that sequence length variants in the Alu-flanking regions as well as nucleotide substitutions are the most common genomic variations even in a region of extreme Alu-clustering. Moreover, the high degree of sequence conservation among three primate species argues against the Alu cluster being the site of frequent genomic rearrangements or other frequent genetic events that might influence NRAMP1 expression.
Mammalian Genome – Springer Journals
Published: Jun 1, 1998
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