INTRODUCTION

Restriction fragment length polymorphisms (RFLPs) result from DNA base-pair changes that introduce or remove a restriction site, or sequence deletions, additions or rearrangments, that affect the length of DNA between sites. RFLPs promise to be useful in a number of different ways. Their utilisation as ‘genetic signposts’ should eventually permit the saturation of the human genome with evenly-spaced marker loci (White et al, 1985). This new system of markers at the DNA level promises to unify mapping at the cytogenetic and molecular levels, greatly improve the resolution so necessary for accurate gene mapping and linkage studies and give a new perspective on genetic variation. The improved linkage map should provide sufficient markers to localize and diagnose many hitherto undetectable genetic defects and allow the identification of heterozygous carriers.

This article describes a search for RFLPs in the human genome using a random sample of cloned DNA segments. Analysis of the data has permitted a first estimate of heterozygosity in the human genome, an amount large enough to demonstrate the extensive variation which can be exploited in clinical medicine. The clinical applications of recombinant DNA technology to the analysis and diagnosis of human genetic disease are then presented. RFLPs associated either with gene regions or linked DNA segments may permit antenatal diagnosis in cases where it has not proved possible to detect gene defects directly using a cloned gene probe.