Detecting and estimating contamination of human DNA samples in sequencing and array-based genotype data

DNA sample contamination is a serious problem in DNA sequencing studies and may result in systematic genotype misclassification and false positive associations. Although methods exist to detect and filter out cross-species contamination, few methods to detect within-species sample contamination are...

Full description

Saved in:
Bibliographic Details
Published in:American journal of human genetics Vol. 91; no. 5; p. 839
Main Authors: Jun, Goo, Flickinger, Matthew, Hetrick, Kurt N, Romm, Jane M, Doheny, Kimberly F, Abecasis, Gonçalo R, Boehnke, Michael, Kang, Hyun Min
Format: Journal Article
Language:English
Published: United States 02.11.2012
Subjects:
Diabetes Mellitus, Type 2 - diagnosis
Diabetes Mellitus, Type 2 - genetics
DNA Contamination
Genotype
Humans
Sequence Analysis, DNA
ISSN:1537-6605, 1537-6605
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:DNA sample contamination is a serious problem in DNA sequencing studies and may result in systematic genotype misclassification and false positive associations. Although methods exist to detect and filter out cross-species contamination, few methods to detect within-species sample contamination are available. In this paper, we describe methods to identify within-species DNA sample contamination based on (1) a combination of sequencing reads and array-based genotype data, (2) sequence reads alone, and (3) array-based genotype data alone. Analysis of sequencing reads allows contamination detection after sequence data is generated but prior to variant calling; analysis of array-based genotype data allows contamination detection prior to generation of costly sequence data. Through a combination of analysis of in silico and experimentally contaminated samples, we show that our methods can reliably detect and estimate levels of contamination as low as 1%. We evaluate the impact of DNA contamination on genotype accuracy and propose effective strategies to screen for and prevent DNA contamination in sequencing studies.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1537-6605
1537-6605
DOI:10.1016/j.ajhg.2012.09.004