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

Area of Science:

• Genetics
• Genomics
• Statistical Genetics

Background:

• Genomewide linkage scans traditionally use microsatellite markers at ~10 cM intervals.
• Single-nucleotide polymorphisms (SNPs) offer potential for higher resolution genetic mapping.
• Marker density and heterozygosity/minor allele frequency impact linkage analysis power.

Purpose of the Study:

• To simulate and compare the information content of microsatellite and SNP maps for linkage detection.
• To evaluate the effect of marker density and allele frequencies on inheritance information.
• To assess map performance with and without parental genotypes in various family structures.

Main Methods:

• Performed simulations varying microsatellite density (0.5-10 cM) and heterozygosity (2-20 alleles).
• Simulated SNP density (0.1-1 cM) and minor allele frequency (0.01-0.5).
• Calculated information content for sib pairs, trios, and quads, with and without parental genotypes.

Main Results:

• With parental genotypes, 2 cM microsatellite or 1 SNP/cM maps captured >95% information.
• Without parental genotypes, denser maps (both SNP and microsatellite) maximized inheritance information.
• Traditional ~10 cM microsatellite maps had significantly lower information content than dense SNP maps.

Conclusions:

• Dense SNP maps provide equal or superior power for linkage detection compared to sparse microsatellite maps.
• Reanalysis of previous linkage studies using denser marker maps could yield substantial benefits.
• Marker density is critical for maximizing genetic information, particularly in the absence of parental data.