title: Genome measures used for quality control are dependent on gene function and ancestry.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  yan.guo@vanderbilt.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Center for Quantitative Sciences and Department of Medicine and Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Center for Quantitative Sciences and Department of Medicine and Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Raskin
authors.affiliation: Center for Quantitative Sciences and Department of Medicine and Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.affiliation: Center for Quantitative Sciences and Department of Medicine and Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.affiliation: Center for Quantitative Sciences and Department of Medicine and Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37212, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
mesh_terms: D019143:Evolution, Molecular; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011786:Quality Control