Isolation and analysis of DNA marker revealing restriction fragment length polymorphism from X chromosome specific DNA library.

A human X chromosome specific DNA library was constructed from flow sorted metaphase X chromosomes. Twenty eight single-copy containing phage clones from this X chromosome library were tested for polymorphism against a panel of DNAs from several unrelated individuals, digested with eight restriction enzymes. One (named lambda 33) of these phage clones revealed high frequency two allele polymorphism with the restriction enzyme Msp I and was regionally mapped to the chromosome Xpter by two methods, including Southern analysis with a mapping panel of cell hybrids and quantitative hybridization. The polymorphism appears to be the result of base pair substitutions or modifications rather than DNA rearrangements. In order to examine the heritability of two alleles, the DNAs from four members of a family spanning three generations were examined. The alleles are consistent with their inheritance as a classic X-linked Mendelian locus. Probe lambda 33 will serve as a marker for linkage studies with known polymorphic loci as well as to establish linkage with X-linked diseases.