The effect of selective sampling on mapping quantitative trait loci.
Sib pairs were selectively sampled for extreme concordance or discordance for the quantitative trait Q1, a simulated phenotype (GAW10). Two selective sampling criteria were used (SC1 and SC2), and results for these were compared to linkage analyses using all pairs (ALL). In total 773 sib pairs were available, which reduced to an average of 59.7 pairs under SC1, and 134.1 pairs under SC2. Whole genome screens were performed on 10 different data replicates for each selection criterion (ALL, SC1, and SC2). Fine screens were then performed over regions which indicated at least suggestive linkage, and these regions were also fine screened in an independent data replicate in an attempt to repeat any areas found. The results for the coarse genome screens were similar under each of the criteria, although in general lower maxima and slightly more erratic lods were found under the stricter selection methods. The correct region on chromosome 5 (responsible for approximately 22% of the variance of Q1) was detected (p < 0.0001) in 6/10 of the data replicates using ALL, and 4/10 using SC1 and SC2. The second quantitative trait locus (QTL) on chromosome 8 (only 0.5% of the variance of Q1) was detected in only a single data replicate using SC1. False positive rates were similar for each criterion, whereas power decreased using selective sampling compared to ALL, although this was probably due to an insufficient initial sample size.
Camp
N J
NJ
Section of Molecular Medicine, University of Sheffield, UK.
Bansal
A
A
D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008957:Models, Genetic; D009679:Nuclear Family; D010641:Phenotype; D011237:Predictive Value of Tests; D019655:Quantitative Trait, Heritable; D012494:Sampling Studies; D012984:Software