Impact of Measurement Errors in Haplotyping in DNA Pooling

• Activity Number: 326
• Type: Topic Contributed
• Date/Time: Wednesday, August 11, 2004 : 10:30 AM to 12:20 PM
• Sponsor: ENAR
• Author(s): Hemant K. Tiwari*+
• Companies: University of Alabama, Birmingham
• Keywords: association ; candidate genes ; complex diseases ; DNA pooling ; haplotyping ; measurement errors

Abstract

DNA pooling has been proposed as an efficient method to perform large scale association studies for a genome scans or candidate gene analyses with a dense set of markers. The use of DNA pooling has potential for gene-mapping and reduces the genotyping cost considerably. Although, there is a substantial reduction of cost in genotyping, there are several methodological issues that can confound the findings. The estimate of an allele frequency in a pooling experiment is subject to errors due to DNA quantification and formation of pools; amplification of target sequence; frequency estimation with chosen methodology; and sampling variance. It has been shown that haplotype analysis has greater statistical power than single point analysis. However, the extent to which misspecification of allele frequency estimate due to DNA pooling affects haplotype inference has not been rigorously investigated to date. We investigate effect of DNA pooling on haplotype frequencies estimation and then we investigate impact of misspecification of allele frequencies on Type I error and power of the haplotype association test.