Genotyping DNA pools on microarrays: tackling the QTL problem of large samples and large numbers of SNPs.
BACKGROUND
Quantitative trait locus (QTL) theory predicts that genetic influence on complex traits involves multiple genes of small effect size. To detect QTL associations of small effect size, large samples and systematic screens of thousands of DNA markers are required. An efficient solution is to genotype case and control DNA pools using SNP microarrays. We demonstrate that this is practical using DNA pools of 100 individuals.


RESULTS
Using standard microarray protocols for the Affymetrix GeneChip Mapping 10 K Array Xba 131, we show that relative allele signal (RAS) values provide a quantitative index of allele frequencies in pooled DNA that correlate 0.986 with allele frequencies for 104 SNPs that were genotyped individually for 100 individuals. The sensitivity of the assay was demonstrated empirically in a spiking experiment in which 15% and 20% of one individual's DNA was added to a DNA pool.


CONCLUSIONS
We conclude that this approach, which we call SNP-MaP (SNP microarrays and pooling), is rapid, cost effective and promises to be a valuable initial screening method in the hunt for QTLs.
Meaburn
Emma
E
Social, Genetic and Developmental Psychiatry Centre, Box Number P082, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK. e.meaburn@iop.kcl.ac.uk
Butcher
Lee M
LM
Liu
Lin
L
Fernandes
Cathy
C
Hansen
Valerie
V
Al-Chalabi
Ammar
A
Plomin
Robert
R
Craig
Ian
I
Schalkwyk
Leonard C
LC
D000483:Alleles; D002874:Chromosome Mapping; D017931:DNA Primers / Q000737:chemistry; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000191:economics / Q000379:methods*; D012984:Software
D017931:DNA Primers