Generation of variability at VNTR loci in human DNA.
Our laboratory has constructed linkage maps of the human chromosomes to use as a tool towards the goal of cloning by position the genes responsible for genetic disorders. Construction of the map required the development of polymorphic marker systems in the form of Restriction Fragment Length Polymorphisms (RFLPs). Work by Yusuke Nakamura in the laboratory led to the identification of more than 200 highly informative Variable Number Tandem Repeat (VNTR) markers. The hypervariable nature of these marker loci has allowed individualization at the DNA level. Techniques for individualization have subsequently been adopted by diverse fields including gene mapping, cancer genetics and forensic biology. These markers have also become a resource to test hypotheses as to how the VNTRs generate their intrinsic variability. We have demonstrated that the hypothesis that VNTRs generate their variability by unequal exchange between homologous chromosomes in incorrect (Wolff et al., 1988; Wolff et al., 1989). Our data are consistent with intrachromosomal models such as unequal sister chromatid exchange and replication slippage. Using DNA derived from nonhuman primate species, we have tested hypotheses that try to explain the sequence relationship at dispersed VNTR loci. Our data reveal that VNTR loci are most likely not related by transposition but rather arose independently at multiple loci.
Wolff
R
R
Department of Human Genetics, University of Utah Medical Center, Salt Lake City 84132.
Nakamura
Y
Y
Odelberg
S
S
Shiang
R
R
White
R
R
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D003434:Crossing Over, Genetic; D004276:DNA, Satellite; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008969:Molecular Sequence Data; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid
D004276:DNA, Satellite; D005819:Genetic Markers