HIGH-RESOLUTION LINKAGE MAP OF MOUSE CHROMOSOME-13 IN THE VICINITY OFTHE HOST-RESISTANCE LOCUS LGN1

Natural resistance of inbred mouse strains to infection with Legionell a pneumophila is controlled by the expression of a single dominant gen e on chromosome 13, designated Lgn1. The genetic difference at Lgn1 is phenotypically expressed as the presence or absence of intracellular replication of L. pneumophila in host macrophages. In our effort to id entify the Lgn1 gene by positional cloning, we have generated a high-r esolution linkage map of the Lgn1 chromosomal region. For this, we hav e carried out extensive segregation analysis in a total of 1270 (A/J x C57BL/6J) x A/J informative backcross mice segregating the resistance allele of C57BL/6J and the susceptibility allele of A/J. Additional s egregation analyses were carried out in three preexisting panels of C5 7BL/6J x Mus spretus interspecific backcross mice. A total of 39 DNA m arkers were mapped within an interval of approximately 30 cM overlappi ng the Lgn1 region. Combined pedigree analyses for the 5.4-cM segment overlapping Lgn1 indicated the locus order and the interlocus distance s (in cM): 1)-D13Mit147-(0.9)-D13Mit36-(0.9)-D13Mit146-(0.2)- Lgn1/D13 Mit37-(1.0)-D13Mit70. Additional genetic linkage studies of markers no t informative in the A/J x C57BL/6J cross positioned D13Mit30, -72, -1 95, and -203, D13Gor4, D13Hun35, and Mtap5 in the immediate vicinity o f the Lgn1 locus. The marker density and resolution of this genetic li nkage map should allow the construction of a physical map of the regio n and the isolation of YAC clones overlapping the gene. (C) 1997 Acade mic Press.