Linkage analysis by two-dimensional DNA typing.
In two-dimensional (2-D) DNA typing, genomic DNA fragments are separated, first according to size by electrophoresis in a neutral polyacrylamide gel and second according to sequence by denaturing gradient gel electrophoresis, followed by hybridization analysis using micro- and minisatellite core probes. The 2-D DNA typing method generates a large amount of information on polymorphic loci per gel. Here we demonstrate the potential usefulness of 2-D DNA typing in an empirical linkage study on the red factor in cattle, and we show an example of the 2-D DNA typing analysis of a human pedigree. The power efficiency of 2-D DNA typing in general is compared with that of single-locus typing by simulation. The results indicate that, although 2-D DNA typing is very efficient in generating data on polymorphic loci, its power to detect linkage is lower than single-locus typing, because it is not obvious whether a spot represents the presence of one or two alleles. It is possible to compensate for this lower informativeness by increasing the sample size. Genome scanning by 2-D DNA typing has the potential to be more efficient than current genotyping methods in scoring polymorphic loci. Hence, it could become a method of choice in mapping genetic traits in humans and animals.
te Meerman
G J
GJ
Department of Medical Genetics, University of Groningen, The Netherlands.
Mullaart
E
E
van der Meulen
M A
MA
den Daas
J H
JH
Morolli
B
B
Uitterlinden
A G
AG
Vijg
J
J
D000483:Alleles; D000818:Animals; D002417:Cattle / Q000235:genetics*; D002874:Chromosome Mapping; D003198:Computer Simulation; D004247:DNA / Q000032:analysis*; D015342:DNA Probes; D004276:DNA, Satellite; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D010858:Pigmentation / Q000235:genetics; D011110:Polymorphism, Genetic
D015342:DNA Probes; D004276:DNA, Satellite; D004247:DNA