Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples

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http://hdl.handle.net/10138/167558

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Wang , J , Skoog , T , Einarsdottir , E , Kaartokallio , T , Laivuori , H , Grauers , A , Gerdhem , P , Hytonen , M , Lohi , H , Kere , J & Jiao , H 2016 , ' Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples ' , Scientific Reports , vol. 6 , 33256 . https://doi.org/10.1038/srep33256

Title: Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples
Author: Wang, Jingwen; Skoog, Tiina; Einarsdottir, Elisabet; Kaartokallio, Tea; Laivuori, Hannele; Grauers, Anna; Gerdhem, Paul; Hytonen, Marjo; Lohi, Hannes; Kere, Juha; Jiao, Hong
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Veterinary Genetics
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
Date: 2016-09-16
Language: eng
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/167558
Abstract: High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies.
Subject: INTEGRATIVE GENOMICS VIEWER
MASSIVELY-PARALLEL DNA
SUSCEPTIBILITY GENE
EXOME
PREECLAMPSIA
ASSOCIATION
FAMILIES
CAPTURE
DISEASE
LINKAGE
3111 Biomedicine
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