We have developed a multiplex method of genome analysis, restriction l
andmark genomic scanning (RLGS) that has been used to construct geneti
c maps in mice. Restriction landmarks are end-labeled restriction frag
ments of genomic DNA that are separated by using high resolution, two-
dimensional gel electrophoresis identifying as many as two thousand la
ndmark loci in a single gel. Variation for several hundred of these lo
ci has been identified between laboratory strains and between these st
rains and Mus spretus. The segregation of more than 1100 RLGS loci has
been analyzed in recombinant inbred (RI) strains and in two separate
interspecific genetic crosses. Genetic maps have been derived that lin
k 1045 RLGS loci to reference loci an all of the autosomes and the X c
hromosome of the mouse genome. The RLGS method can be applied to genom
e analysis in many different organisms to identify genomic loci becaus
e it uses end-labeling of restriction landmarks rather than probe hybr
idization. Different combinations of restriction enzymes yield differe
nt sets of RLGS loci providing expanded power for genetic mapping.