Genome measures used for quality control are dependent on gene function and ancestry.

Wang J, Raskin L, Samuels DC, Shyr Y, Guo Y
Bioinformatics. 2015 31 (3): 318-23

PMID: 25297068 · PMCID: PMC4308666 · DOI:10.1093/bioinformatics/btu668

MOTIVATION - The transition/transversion (Ti/Tv) ratio and heterozygous/nonreference-homozygous (het/nonref-hom) ratio have been commonly computed in genetic studies as a quality control (QC) measurement. Additionally, these two ratios are helpful in our understanding of the patterns of DNA sequence evolution.

RESULTS - To thoroughly understand these two genomic measures, we performed a study using 1000 Genomes Project (1000G) released genotype data (N=1092). An additional two datasets (N=581 and N=6) were used to validate our findings from the 1000G dataset. We compared the two ratios among continental ancestry, genome regions and gene functionality. We found that the Ti/Tv ratio can be used as a quality indicator for single nucleotide polymorphisms inferred from high-throughput sequencing data. The Ti/Tv ratio varies greatly by genome region and functionality, but not by ancestry. The het/nonref-hom ratio varies greatly by ancestry, but not by genome regions and functionality. Furthermore, extreme guanine + cytosine content (either high or low) is negatively associated with the Ti/Tv ratio magnitude. Thus, when performing QC assessment using these two measures, care must be taken to apply the correct thresholds based on ancestry and genome region. Failure to take these considerations into account at the QC stage will bias any following analysis.


SUPPLEMENTARY INFORMATION - Supplementary data are available at Bioinformatics online.

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MeSH Terms (9)

Evolution, Molecular Genome, Human Genome-Wide Association Study Genotype High-Throughput Nucleotide Sequencing Humans Phenotype Polymorphism, Single Nucleotide Quality Control

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