Microsatellites versus single-nucleotide polymorphisms in linkage analysis for quantitative and qualitative measures.
BACKGROUND
Genetic maps based on single-nucleotide polymorphisms (SNP) are increasingly being used as an alternative to microsatellite maps. This study compares linkage results for both types of maps for a neurophysiology phenotype and for an alcohol dependence phenotype. Our analysis used two SNP maps on the Illumina and Affymetrix platforms. We also considered the effect of high linkage disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP map obtained by dropping some markers in high LD with other markers in those regions.


RESULTS
The neurophysiology phenotype at the main linkage peak near 130 MB gave LOD scores of 2.76, 2.53, 3.22, and 2.68 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. The alcohol dependence phenotype at the main linkage peak near 101 MB gave LOD scores of 3.09, 3.69, 4.08, and 4.11 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively.


CONCLUSIONS
The linkage results were stronger overall for SNPs than for microsatellites for both phenotypes. However, LOD scores may be artificially elevated in regions of high LD. Our analysis indicates that appropriately thinning a SNP map in regions of high LD should give more accurate LOD scores. These results suggest that SNPs can be an efficient substitute for microsatellites for linkage analysis of both quantitative and qualitative phenotypes.
Dunn
Gerald
G
Department of Psychiatry, Genetics, Washington University School of Medicine, St. Louis, Missouri, USA. dunnge@notes.wustl.edu
Hinrichs
Anthony L
AL
Bertelsen
Sarah
S
Jin
Carol H
CH
Kauwe
John S K
JS
Suarez
Brian K
BK
Bierut
Laura J
LJ
D000437:Alcoholism / Q000235:genetics / Q000503:physiopathology; D002874:Chromosome Mapping; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics*; D009424:Nervous System Physiological Phenomena; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*