Aug 13, 2013

Genotype imputation reference panel selection using maximal phylogenetic diversity

Genetics
Peng ZhangSebastian Zöllner

Abstract

The recent dramatic cost reduction of next-generation sequencing technology enables investigators to assess most variants in the human genome to identify risk variants for complex diseases. However, sequencing large samples remains very expensive. For a study sample with existing genotype data, such as array data from genome-wide association studies, a cost-effective approach is to sequence a subset of the study sample and then to impute the rest of the study sample, using the sequenced subset as a reference panel. The use of such an internal reference panel identifies population-specific variants and avoids the problem of a substantial mismatch in ancestry background between the study population and the reference population. To efficiently select an internal panel, we introduce an idea of phylogenetic diversity from mathematical phylogenetics and comparative genomics. We propose the "most diverse reference panel", defined as the subset with the maximal "phylogenetic diversity", thereby incorporating individuals that span a diverse range of genotypes within the sample. Using data both from simulations and from the 1000 Genomes Project, we show that the most diverse reference panel can substantially improve the imputation accura...Continue Reading

  • References28
  • Citations10

References

Mentioned in this Paper

Genome-Wide Association Study
Genome
Phylogeny
Computer Programs and Programming
Genomics
Sequencing
Massively-Parallel Sequencing
Genetic Equilibrium
Genome, Human
Genotype Determination

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