title: Association testing by DNA pooling: an effective initial screen.
abstract: With an ever-increasing resource of validated single-nucleotide polymorphisms (SNPs), the limiting factors in genome-wide association analysis have become genotyping capacity and the availability of DNA. We provide a proof of concept of the use of pooled DNA as a means of efficiently screening SNPs and prioritizing them for further study. This approach reduces the final number of SNPs that undergo full, sample-by-sample genotyping as well as the quantity of DNA used overall. We have examined 15 SNPs in the cholesteryl ester transfer protein (CETP) gene, a gene previously demonstrated to be associated with serum high-density lipoprotein cholesterol levels. The SNPs were amplified in two pools of DNA derived from groups of individuals with extremely high and extremely low serum high-density lipoprotein cholesterol levels, respectively. P values <0.05 were obtained for 14 SNPs, supporting the described association. Genotyping of the individual samples showed that the average margin of error in frequency estimate was approximately 4% when pools were used. These findings clearly demonstrate the potential of pooling techniques and their associated technologies as an initial screen in the search for genetic associations.
authors.affiliation: SEQUENOM-Gemini Ltd., 162 Cambridge Science Park, Milton Road, Cambridge, CB4 0GH England.
authors.forename: Aruna
authors.initials: A
authors.lastname: Bansal
authors.forename: Dirk
authors.initials: D
authors.lastname: van den Boom
authors.forename: Stefan
authors.initials: S
authors.lastname: Kammerer
authors.forename: Christiane
authors.initials: C
authors.lastname: Honisch
authors.forename: Gail
authors.initials: G
authors.lastname: Adam
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: Patrick
authors.initials: P
authors.lastname: Kleyn
authors.forename: Andi
authors.initials: A
authors.lastname: Braun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D005260:Female; D005788:Gene Pool; D006023:Glycoproteins; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins