Imputation reliability on DNA biallelic markers for drug metabolism studies

BMC Bioinformatics

Research

Marco Sazzini¹  Giovanni Martinelli²  Ilaria Iacobucci²  Luciano Xumerle³  Vladan Mijatovic³  Giovanni Malerba³  Antonio Mori³  Pier Franco Pignatti³ 

[1] Dep. of Experimental Evolutionary Biology, University of Bologna, via Selmi 3, 40126, Bologna, Italy;Dep. of Hematology and Oncological Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy;Dep. of Life and Reproductions Sciences, Sec. of Biology and Genetics - University of Verona, strada Le grazie 8, 37134, Verona, Italy;

关键词: Acute Myeloid Leukemia;    Drug Metabolism;    Minor Allele Frequency;    Reference Panel;    Imputation Accuracy;   

DOI  :  10.1186/1471-2105-13-S14-S7

来源: Springer

【 摘 要 】

BackgroundImputation is a statistical process used to predict genotypes of loci not directly assayed in a sample of individuals. Our goal is to measure the performance of imputation in predicting the genotype of the best known gene polymorphisms involved in drug metabolism using a common SNP array genotyping platform generally exploited in genome wide association studies.MethodsThirty-nine (39) individuals were genotyped with both Affymetrix Genome Wide Human SNP 6.0 (AFFY) and Affymetrix DMET Plus (DMET) platforms. AFFY and DMET contain nearly 900000 and 1931 markers respectively. We used a 1000 Genomes Pilot + HapMap 3 reference panel. Imputation was performed using the computer program Impute, version 2. SNPs contained in DMET, but not imputed, were analysed studying markers around their chromosome regions. The efficacy of the imputation was measured evaluating the number of successfully imputed SNPs (SSNPs).ResultsThe imputation predicted the genotypes of 654 SNPs not present in the AFFY array, but contained in the DMET array. Approximately 1000 SNPs were not annotated in the reference panel and therefore they could not be directly imputed. After testing three different imputed genotype calling threshold (IGCT), we observed that imputation performs at its best for IGCT value equal to 50%, with rate of SSNPs (MAF > 0.05) equal to 85%.ConclusionsMost of the genes involved in drug metabolism can be imputed with high efficacy using standard genome-wide genotyping platforms and imputing procedures.

【 授权许可】

Unknown   
© Mijatovic et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.