Equivalence of single- and multilocus markers: power to detect linkage with composite markers derived from biallelic loci.
The reintroduction of biallelic markers, now in the form of single-nucleotide polymorphisms (SNPs), has again raised concerns about the practicality of the use of markers with low heterozygosity for genomic screening for complex traits, even if thousands of such markers are available. Like the early blood-group markers (e.g., Rh and MNS), tightly linked biallelic SNPs can be combined into composite markers with heterozygosity similar to that of short-tandem-repeat polymorphisms. The assumptions that underlie the equivalence between single-locus multiallelic and composite markers are presented. We used computer simulation to determine the power of the Haseman-Elston test for linkage with composite markers when not all of these assumptions hold. The Genometric Analysis Simulation Program was used to simulate continuous and discrete traits, one single-locus four-allele marker, and six biallelic markers. We studied composite markers created from pairs, trios, and quartets of biallelic markers in nuclear families and in independent sib pairs. The power to detect linkage with a two-point approach for composite markers and with a multipoint approach that incorporated all six biallelic markers was compared with that for a single-locus, four-allele reference marker. Although the power to detect linkage with a single biallelic marker was considerably less than that of the reference marker, the power to detect linkage with two- and three-locus composite markers was quite similar to that of the reference marker. The power to detect linkage with four-locus composite markers was similar to that of a multipoint approach.
Wilson
A F
AF
Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, MD 21224, USA. afw@nhgri.nih.gov.
Sorant
A J
AJ
D000483:Alleles; D002874:Chromosome Mapping / Q000379:methods* / Q000706:statistics & numerical data; D003198:Computer Simulation; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D016555:Matched-Pair Analysis; D008957:Models, Genetic; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012680:Sensitivity and Specificity; D012984:Software
D005819:Genetic Markers