Abstract
Genotype data from the Illumina Linkage III SNP panel (n = 4,720 SNPs) and the Affymetrix 10 k mapping array (n = 11,120 SNPs) were used to test the effects of linkage disequilibrium (LD) between SNPs in a linkage analysis in the Collaborative Study on the Genetics of Alcoholism pedigree collection (143 pedigrees; 1,614 individuals). The average r2 between adjacent markers across the genetic map was 0.099 ± 0.003 in the Illumina III panel and 0.17 ± 0.003 in the Affymetrix 10 k array. In order to determine the effect of LD between marker loci in a nonparametric multipoint linkage analysis, markers in strong LD with another marker (r2 > 0.40) were removed (n = 471 loci in the Illumina panel; n = 1,804 loci in the Affymetrix panel) and the linkage analysis results were compared to the results using the entire marker sets. In all analyses using the ALDX1 phenotype, 8 linkage regions on 5 chromosomes (2, 7, 10, 11, X) were detected (peak markers p < 0.01), and the Illumina panel detected an additional region on chromosome 6. Analysis of the same pedigree set and ALDX1 phenotype using short tandem repeat markers (STRs) resulted in 3 linkage regions on 3 chromosomes (peak markers p < 0.01). These results suggest that in this pedigree set, LD between loci with spacing similar to the SNP panels tested may not significantly affect the overall detection of linkage regions in a genome scan. Moreover, since the data quality and information content are greatly improved in the SNP panels over STR genotyping methods, new linkage regions may be identified due to higher information content and data quality in a dense SNP linkage panel.
Highlights
For many years short tandem repeat (STR) or microsatellite markers have been used as the standard genetic markers for linkage mapping [1,2,3,4,5]
Inter-marker linkage disequilibrium (LD) LD strength (r2) between each adjacent marker pair on the genetic map was evaluated in both single-nucleotide polymorphism (SNP) panels
The results on this study suggest that LD between loci in a linkage analysis does not significantly affect the overall detection of linkage regions in a genome scan
Summary
For many years short tandem repeat (STR) or microsatellite markers have been used as the standard genetic markers for linkage mapping [1,2,3,4,5]. STRs typically have a high degree of heterozygosity and provide high information content per marker [6]. They occur widely throughout the genome, with over 5,000 STRs being mapped to a highresolution genetic map [5]. A drawback to using microsatellite markers is that because of the large number of alleles differing by as few as 2 to 4 bp, analysis has required electrophoretic separation. Because of this technical limitation, their analysis is time consuming and not amenable to highly multiplexed, automated formats. There is an (page number not for citation purposes)
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