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Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools

Norton, Nadine, Williams, Nigel Melville ORCID:, Williams, Hywel J., Spurlock, Gillian, Kirov, George ORCID:, Morris, Derek W., Hoogendoorn, Bastiaan ORCID:, Owen, Michael John ORCID: and O'Donovan, Michael Conlon ORCID: 2002. Universal, robust, highly quantitative SNP allele frequency measurement in DNA pools. Human Genetics 110 (5) , pp. 471-478. 10.1007/s00439-002-0706-6

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Detecting alleles that confer small increments in susceptibility to disease will require large-scale allelic association studies of single-nucleotide polymorphisms (SNPs) in candidate, or positional candidate, genes. However, current genotyping technologies are one to two orders of magnitude too expensive to permit the analysis of thousands of SNPs in large samples. We have developed and thoroughly validated a highly accurate protocol for SNP allele frequency estimation in DNA pools based upon the SNaPshot (Applied Biosystems) chemistry adaptation of primer extension. Using this assay, we were able to estimate the difference in allele frequencies between pooled cases and controls (Delta) with a mean error of 0.01. Moreover, when we genotyped seven different SNPs in a single multiplex reaction, the results were similar, with a mean error for Delta of 0.008. The assay performed well for alleles of low frequency alleles (f approximately 0.05) and was accurate even with relatively poor quality DNA template extracted from mouthwashes. Our assay conditions are generalisable, universal, robust and, therefore, for the first time, permit high-throughput association analysis at a realistic cost.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Springer Verlag (Germany)
ISSN: 0340-6717
Last Modified: 16 Feb 2023 14:59

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