Guidelines for genotyping in genomewide linkage studies: single-nucleotide-polymorphism maps versus microsatellite maps

Evans, David M. and Cardon, Lon R. (2004) Guidelines for genotyping in genomewide linkage studies: single-nucleotide-polymorphism maps versus microsatellite maps. American Journal of Human Genetics, 75 4: 687-692. doi:10.1086/424696


Author Evans, David M.
Cardon, Lon R.
Title Guidelines for genotyping in genomewide linkage studies: single-nucleotide-polymorphism maps versus microsatellite maps
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 0002-9297
1537-6605
Publication date 2004-10-01
Year available 2004
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1086/424696
Open Access Status Not yet assessed
Volume 75
Issue 4
Start page 687
End page 692
Total pages 6
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Abstract Genomewide linkage scans have traditionally employed panels of microsatellite markers spaced at intervals of ∼10 cM across the genome. However, there is a growing realization that a map of closely spaced single-nucleotide polymorphisms (SNPs) may offer equal or superior power to detect linkage, compared with low-density microsatellite maps. We performed a series of simulations to calculate the information content associated with microsatellite and SNP maps across a range of different marker densities and heterozygosities for sib pairs (with and without parental genotypes), sib trios, and sib quads. In the case of microsatellite markers, we varied density across 11 levels (1 marker every 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 cM) and marker heterozygosity across 6 levels (2, 3, 4, 5, 10, or 20 equally frequent alleles), whereas, in the case of SNPs, we varied marker density across 4 levels (1 marker every 0.1, 0.2, 0.5, or 1 cM) and minor-allele frequency across 7 levels (0.5, 0.4, 0.3, 0.2, 0.1, 0.05, and 0.01). When parental genotypes were available, a map consisting of microsatellites spaced every 2 cM or a relatively sparse map of SNPs (i.e., at least 1 SNP/cM) was sufficient to extract most of the inheritance information from the map (>95% in most cases). However, when parental genotypes were unavailable, it was important to use as dense a map of markers as possible to extract the greatest amount of inheritance information. It is important to note that the information content associated with a traditional map of microsatellite markers (i.e., 1 marker every ∼10 cM) was significantly lower than the information content associated with a dense map of SNPs or microsatellites. These results strongly suggest that previous linkage studies that employed sparse microsatellite maps could benefit substantially from reanalysis by use of a denser map of markers.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID EY-126562
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collection: UQ Diamantina Institute Publications
 
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