title: 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.
abstract: Recent interest has focused on the region of conserved synteny between mouse chromosome 1 and human 2q33-q37, particularly over the region encoding the murine macrophage resistance gene Ity/Lsh/Bcg (candidate Nramp) and members of the Il8r interleukin-8 (IL8) receptor gene cluster. In this paper, identification of a restriction fragment length polymorphism in the IL8RB gene in 35 pedigrees previously typed for markers in the 2q33-q37 interval provided evidence (lod scores > 3) for linkage between IL8RB and the 2q34-q35 markers FN1, TNP1, VIL1, and DES. Physical 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 approximately 3-fold that observed in the mouse. Partial sequencing of NRAMP confirmed the presence of the N-terminal proline/serine-rich putative SH3 binding domain in exon 2 of the human gene. Further analysis of Brazilian leprosy and visceral leishmaniasis pedigrees identified a rare second allele varying in a 9-nucleotide repeat motif of the exon 2 sequence but segregating independently of the disease phenotype.
authors.affiliation: University of Cambridge Clinical School, Department of Medicine, Addenbrooke's Hospital, United Kingdom.
authors.forename: J K
authors.initials: JK
authors.lastname: White
authors.forename: M A
authors.initials: MA
authors.lastname: Shaw
authors.forename: C H
authors.initials: CH
authors.lastname: Barton
authors.forename: D P
authors.initials: DP
authors.lastname: Cerretti
authors.forename: H
authors.initials: H
authors.lastname: Williams
authors.forename: B A
authors.initials: BA
authors.lastname: Mock
authors.forename: N P
authors.initials: NP
authors.lastname: Carter
authors.forename: C S
authors.initials: CS
authors.lastname: Peacock
authors.forename: J M
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D018244:Chromosomes, Artificial, Yeast; D002889:Chromosomes, Human, Pair 2; D017931:DNA Primers; D005091:Exons; D005260:Female; D006801:Humans; D033862:Iron-Binding Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010375:Pedigree; D011110:Polymorphism, Genetic; D011544:Pseudogenes; D018123:Receptors, Interleukin / Q000235:genetics*; D023062:Receptors, Interleukin-8A; D012091:Repetitive Sequences, Nucleic Acid; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D017931:DNA Primers; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D023062:Receptors, Interleukin-8A; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2