RT Journal
A1 Fakhrai-Rad, Hossein
A1 Zheng, Jianbiao
A1 Willis, Thomas D.
A1 Wong, Kee
A1 Suyenaga, Kent
A1 Moorhead, Martin
A1 Eberle, Jim
A1 Thorstenson, Yvonne R.
A1 Jones, Ted
A1 Davis, Ronald W.
A1 Namsaraev, Eugeni
A1 Faham, Malek
T1 SNP Discovery in Pooled Samples With Mismatch Repair Detection
JF Genome Research 
JO Genome Research 
YR 2004 
FD July 01 
VO 14 
IS 7 
SP 1404 
OP 1412 
DO 10.1101/gr.2373904 
UL http://genome.cshlp.org/content/14/7/1404.abstract 
AB A targeted discovery effort is required to identify low frequency single nucleotide polymorphisms (SNPs) in human coding and regulatory regions. We here describe combining mismatch repair detection (MRD) with dideoxy terminator sequencing to detect SNPs in pooled DNA samples. MRD enriches for variant alleles in the pooled sample, and sequencing determines the nature of the variants. By using a genomic DNA pool as a template, ∼100 fragments were amplified and subsequently combined and subjected en masse to the MRD procedure. The variant-enriched pool from this one MRD reaction is enriched for the population variants of all the tested fragments. Each fragment was amplified from the variant-enriched pool and sequenced, allowing the discovery of alleles with frequencies as low as 1% in the initial population. Our results support that MRD-based SNP discovery can be used for large-scale discovery of SNPs at low frequencies in a population.