A highly polymorphic locus in human DNA.

Abstract

A locus in the human genome, not associated with any specific gene, has been found to be a site of restriction fragment length polymorphism. The polymorphism was found by hybridizing a 16-kilobase-pair segment of single-copy human DNA, selected from the human genome library cloned in phage XCH4A, to a Southern transfer of total human DNA digested with EcoRI. DNAs from a number of individuals from within Mormon pedigrees as well as random individuals have been examined. The locus is highly variable, with at least eight alleles present, homozygotes accounting for less than 25% of the individuals examined. The polymorphism appears to be the result of DNA rearrangements rather than base-pair substitutions or modifications. Examination of the DNA from seven members of a family revealed fragment lengths that are consistent with their inheritance as Mendelian alleles through three generations.Because of the scarcity of useful genetic marker loci, the human genetic linkage map has relatively few entries. For a marker locus to be useful in linkage studies, it must be the site of several variants (alleles). With several alleles occurring at reasonable frequencies in the population, parental individuals heterozygous at different marker loci will be common and cosegregation of markers can be scored among their progeny.Almost all polymorphic marker loci thus far identified in humans represent biochemical variations, such as isozymes or cell surface markers. Most of these loci do not have a sufficient number and frequency of alleles to be of general use in linkage studies in families, and many are not appropriate for prenatal diagnosis. A few biochemical and immunological loci having reasonably frequent variants within the human population have been described, however, and shown to be useful for linkage studies and for the resolution of genetic models (1).We have argued (2) that a large number of DNA sequence variations exist in the human population. Some of these should be detectable as variants in the lengths of the DNA fragments produced by a restriction enzyme (restriction fragment length polymorphism or RFLP). These loci will define arbitrary genetic sites, not necessarily associated with any specific genes, and should prove highly suitable as genetic markers. A linkage map of the human can be constructed by determining the pattern of cosegregation of these genetic markers in human pedigrees. A map based on several hundred such loci will have a sufficient marker density to allow the placement of any other locus with reasonable certainty (2, 3). RFLP markers specifically associated with the human ,3-and "y-globin loci have already been reported (4, 5). We will describe here an arbitrary locus showing a significant frequency of DNA sequence variation.In these experiments, the restriction fragments from the DNA of a locus are revealed by hybridization with a radiolabeledThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in...

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