GENETIC AND PHYSICAL MAPPING OF 2Q35 IN THE REGION OF THE NRAMP AND IL8R GENES - IDENTIFICATION OF A POLYMORPHIC REPEAT IN EXON-2 OF NRAMP

Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region e ncoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate N ramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluste r. In this paper, identification of a restriction fragment length poly morphism in the IL8RB gene in 35 pedigrees previously typed for marker s in the 2q33-q37 interval provided evidence (lod scores > 3) for link age between IL8RB and the 2q34-q35 markers FN1, TNP1, VIL1, and DES. P hysical mapping, using yeast artificial chromosomes isolated with VIL1 , confirmed that IL8RA, IL8RB, and the IL8RB pseudogene map within the NRAMP-VIL1 interval, with the physical distance (155 kb) from 5' LSH to 3' VIL1 representing approximate to 3-fold that observed in the mou se. Partial sequencing of NRAMP confirmed the presence of the N-termin al proline/serine-rich putative SH3 binding domain in exon 2 of the hu man gene, Further analysis of Brazilian leprosy and visceral leishmani asis pedigrees identified a rare second allele varying in a 9-nucleoti de repeat motif of the exon 2 sequence but segregating independently o f the disease phenotype. (C) 1994 Academic Press, Inc.