A STRATEGY TO REVEAL HIGH-FREQUENCY RFLPS ALONG THE HUMAN X-CHROMOSOME

Abstract

Fifteen human X-chromosome-specific DNA fragments, localized to particular regions of that chromosome, were used to search for restriction fragment length polymorphisms. A screening panel prepared by digesting DNA from only 2 females and 1 male with 24 restriction enzymes was sufficient to reveal 2-allele polymorphisms among 1/3 of the probes tested. These polymorphisms, as theoretically anticipated, showed minor allele frequencies above 20%, as a rule. Such high-frequency polymorphism allowed identifying females, from pedigrees segregating 3 X-linked diseases, who were multiply heterozygous for polymorphic loci spread throughout the X chromosome. Two of the 24 enzymes tested with these X-specific probes, Msp I and Taq I, generate fragment sizes in DNA-blotting experiments that, on average, are significantly larger than expected from nearest neighbor predicted recognition site frequencies.