title: How well do HapMap SNPs capture the untyped SNPs?
abstract: BACKGROUND
  The recent advancement in human genome sequencing and genotyping has revealed millions of single nucleotide polymorphisms (SNP) which determine the variation among human beings. One of the particular important projects is The International HapMap Project which provides the catalogue of human genetic variation for disease association studies. In this paper, we analyzed the genotype data in HapMap project by using National Institute of Environmental Health Sciences Environmental Genome Project (NIEHS EGP) SNPs. We first determine whether the HapMap data are transferable to the NIEHS data. Then, we study how well the HapMap SNPs capture the untyped SNPs in the region. Finally, we provide general guidelines for determining whether the SNPs chosen from HapMap may be able to capture most of the untyped SNPs.
  
  
  RESULTS
  Our analysis shows that HapMap data are not robust enough to capture the untyped variants for most of the human genes. The performance of SNPs for European and Asian samples are marginal in capturing the untyped variants, i.e. approximately 55%. Expectedly, the SNPs from HapMap YRI panel can only capture approximately 30% of the variants. Although the overall performance is low, however, the SNPs for some genes perform very well and are able to capture most of the variants along the gene. This is observed in the European and Asian panel, but not in African panel. Through observation, we concluded that in order to have a well covered SNPs reference panel, the SNPs density and the association among reference SNPs are important to estimate the robustness of the chosen SNPs.
  
  
  CONCLUSIONS
  We have analyzed the coverage of HapMap SNPs using NIEHS EGP data. The results show that HapMap SNPs are transferable to the NIEHS SNPs. However, HapMap SNPs cannot capture some of the untyped SNPs and therefore resequencing may be needed to uncover more SNPs in the missing region.
authors.affiliation: Bioinformatics Institute, 30 Biopolis Street, 07-01 Matrix, 138671, Singapore. erwint@bii.a-star.edu.sg
authors.forename: Erwin
authors.initials: E
authors.lastname: Tantoso
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Yang
authors.forename: Kuo-Bin
authors.initials: KB
authors.lastname: Li
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D044465:White People / Q000235:genetics