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

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.

Investigation of paternity establishing without the putative father using hypervariable DNA probes

“…For example, the 242 T. YOKOI et al alleles detected by D2S44 probing have been grouped into 28 size classes among Japal:ese population, but these categories do not represent individual alleles. The recognition of single repeat of the core sequence (30 base pair, Nakamura et al, 1987) will be beyond the capability of agarose gel electrophoresis methods. This probe, D2S44, has theoretically over l l0 different repeat units among Japanese population, but this way of increment indication might be a conservative approach for standardization of the fragment size.…”

“…ESTABLISHING PATERNITY WITHOUT THE PUTATIVE FATHER 237 originally developed by Nakamura et al (1987). Chromosomal location of these probes is 2q, 17p, and lp, respectively.…”

“…Another class of polymorphisms is hypervariable polymorphic regions of DNA resulting from a variable number of tandem repeats (VNTR). A common feature of many of these probes is the presence of a short core sequence element which is repeated in tandem along the chromosome and provides variable polymorphism of the locus (Nakamura et al, 1987;Odelberg et al, 1989). They are valuable genetic markers for human linkage maps (Nakamura et al, 1988a, b), parentage test (Jeffreys et al, 1985a;Baird et al, 1986;Allen et al, 1989) and individual identification .…”

Disease Genes and Gene Regulation by microRNAs

“…The work of Nakamura et al [4] and Murray et al [5] made available hundreds of highly informative DNA markers consisting of short repeats that span the human genome. These markers coupled with polymerase chain reaction greatly accelerated mapping the chromosomal location (locus) of genes responsible for disease.…”

A global genome damage score predictive of lung cancer patients outcome

“…Polymorphisms include simple nucleotide repeat polymorphisms (Bell et al, 1982;Jeffreys et al, 1985;Nakamura et al, 1987) and single nucleotide polymorphisms (SNPs) (Botstein et al, 1980). Single nucleotide polymorphisms can be detected by restriction fragment length analysis or by using oligonucleotides as probes that specifically detect target DNA based on single nucleotide variations.…”