S11
Chickens differ greatly in susceptibility to salmonellosis and it is possible
to identify inbred lines of chickens which differ a thousandfold in their
susceptibility to the disease. Resistance is inherited in a fully dominant,
autosomal manner, with resistant chickens better able to contain the
replication of the bacteria within the spleen and liver until an immune
response can be mounted. This closely resembles the pattern of resistance to
salmonellosis in mice, where genetic resistance is mediated by two major loci,
Nramp1 and Lps, located on mouse chromosomes 1 and 4 respectively. In
particular the differences in pathology seen in chickens resemble those seen
for Nramp1. In chickens homologues of Nramp1 and Tnc (a marker for Lps) have
been mapped to chromosomes 7 and 4, and genetic differences at these loci
affect resistance to salmonellosis. However the effects of these loci account
for only part of the observed differences in resistance and it is clear other
loci have major effects. To locate these genes we have mapped progeny of
crosses between inbred lines of chickens 61 and 15I, which are highly resistant
and susceptible to salmonellosis respectively. Genetic mapping of these crosses
has identified a novel resistance gene which accounts for approximately half of
the difference seen between the parental lines. The association of this new
resistance gene, which we have designated SAL1, has now been confirmed in four
other crosses. There are no likely candidate genes currently identified in the
regions equivalent to SAL1 in humans or mice, and work is now in progress to
refine the map location of SAL1 and to construct a YAC from which to isolate
and identify the gene.