Effect of genotyping error in model-free linkage analysis using microsatellite or single-nucleotide polymorphism marker maps.
Errors while genotyping are inevitable and can reduce the power to detect linkage. However, does genotyping error have the same impact on linkage results for single-nucleotide polymorphism (SNP) and microsatellite (MS) marker maps? To evaluate this question we detected genotyping errors that are consistent with Mendelian inheritance using large changes in multipoint identity-by-descent sharing in neighboring markers. Only a small fraction of Mendelian consistent errors were detectable (e.g., 18% of MS and 2.4% of SNP genotyping errors). More SNP genotyping errors are Mendelian consistent compared to MS genotyping errors, so genotyping error may have a greater impact on linkage results using SNP marker maps. We also evaluated the effect of genotyping error on the power and type I error rate using simulated nuclear families with missing parents under 0, 0.14, and 2.8% genotyping error rates. In the presence of genotyping error, we found that the power to detect a true linkage signal was greater for SNP (75%) than MS (67%) marker maps, although there were also slightly more false-positive signals using SNP marker maps (5 compared with 3 for MS). Finally, we evaluated the usefulness of accounting for genotyping error in the SNP data using a likelihood-based approach, which restores some of the power that is lost when genotyping error is introduced.
Thompson
Cheryl L
CL
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA. clw8@cwru.edu
Baechle
Dan
D
Lu
Qing
Q
Mathew
George
G
Song
Yeunjoo
Y
Iyengar
Sudha K
SK
Gray-McGuire
Courtney
C
Goddard
Katrina A B
KA
D002874:Chromosome Mapping / Q000379:methods*; D005189:False Positive Reactions; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D018895:Microsatellite Repeats / Q000235:genetics*; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics; D012107:Research Design