Variable Number of Tandem Repeat (VNTR) Markers for Human Gene Mapping

TLDR

A large collection of informative genetic markers is required for mapping disease genes, but most existing markers have only two alleles; variable number of tandem repeat (VNTR) loci, which generate many fragment lengths due to repeat variation, offer a promising solution. The authors developed single‑copy probes from oligomeric sequences derived from tandem repeat regions of several genes, enabling detection of VNTR loci by restriction enzyme cleavage that yields fragments of varying lengths. The probes identified highly polymorphic VNTR loci that are heterozygous in most individuals, providing linkage information in nearly all families.

Abstract

A large collection of good genetic markers is needed to map the genes that cause human genetic diseases. Although nearly 400 polymorphic DNA markers for human chromosomes have been described, the majority have only two alleles and are thus uninformative for analysis of genetic linkage in many families. A few known marker systems, however, detect loci that respond to restriction enzyme cleavage by producing a fragment that can have many different lengths. This polymorphism is due to variation in the number of tandem repeats of a short DNA sequence. Because most individuals will be heterozygous at such loci, these markers will provide linkage information in almost all families. Ten oligomeric sequences derived from the tandem repeat regions of the myoglobin gene, the zeta-globin pseudogene, the insulin gene, and the X-gene region of hepatitis B virus, were used to develop a series of single-copy probes. These probes revealed new, highly polymorphic genetic loci whose allele sizes reflected variation in the number of tandem repeats.